Herbal Supplements

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Introduction to Herbal Supplements
Aloe vera
Bacopa monnieri (Brahmi)
Black cohosh
Cascara sagrada
Chinese Tonic Herbs
Cnidium monnieri
Clary sage
Coleus forskohlii
Comfry, Comfrey
Dong quai
Evening primrose
Ginkgo biloba
Gotu kola
Grape seed
Green tea
Guggal (Commiphora)
Gymnema sylvestre
Kava kava
Milk thistle
Morus alba (Mulberry)
Phyllanthus niruri
Rauwolfia serpentina
Saw palmetto
St John's wort
Tongkat Ali
Tribulus terrestris
Uva ursi

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Introduction to Herbal Supplements

Plants have been used since the dawn of humanity for medical purposes. Plant extracts or derivatives are used in traditional healing systems such as Chinese herbal medicine, Indian (Ayurvedic) or Japanese (Kampo) medicine, and are practised in Western industrialized countries where their use is often integrated into conventional medicine. The therapeutic value of several herbal medicines has been established, however, for many others this is not the case, often because the research has not been done.












Many persons who use herbal supplements believe that these medicines are natural and therefore safe, but this is a dangerous oversimplification. Some herbal medicines are associated with adverse effects, which include interactions with prescribed drugs. Many of these adverse herbal supplement prescription drug interactions are described for each herb described here. A recent survey found that 15% of patients receiving conventional drug therapies also take herbal supplements and, among these, potential adverse herb-drug interactions were observed in 40% of patients. Only about one third of patients taking prescription medications and herbal supplements tell their physician about this use. This lack of information, combined with the fact that herbal medicines are usually a mixture of many active ingredients, increases the likelihood of harm.

The vast majority of herbal supplements as well as Chinese and Indian herbal medicines exert their effects due to the presence of numerous antioxidant compounds such as the polyphenols. The specifics of plant-derived antioxidant compounds is covered in detail in the Antioxidants page. Just in the area of herbal medicines associated with anticancer activity there are over 400 different species of Chinese medicinal herb. Given the extremely large numbers of various herbal supplements, this page will only briefly describe several of the more commonly found medicinal herbs.

When discussing dietary herbal supplements it is important to remember that there are currently no stringent regulatory controls governing the production processes and sale of these supplements. Currently, supplements containing ephedrine are banned from sale in the US as are oral preparations of supplements derived from comfrey (see below). Recently the Consumer Reports issued a warning listing 12 dietary supplements (not all are herbal supplements) that contain compounds that can cause cancer, liver disease, kidney damage, or heart disease. These supplements are aconite, bitter orange, chaparral, colloidal silver, coltsfoot, comfrey, country mallow, germanium, greater celandine, kava, lobelia and yohimbe

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Aloe vera: Aloe vera Linne or aloe barbadensis Miller is a succulent from the Aloe family of which there are 400 different species. The species name vera means "genuine". Present in Aloe plants are two compounds, aloin and aloe-emodin, that have been shown to have anti-inflammatory properties which could explain their utility in the treatment of the discomfort associated with mild sunburn. Emodins are anthraquinones found in the rhizomes of numerous plant species (see cascara sagrada below). Aloin is a crystalline chemical extracted from the tissues just under the skin of various aloes.

In mouse white blood cells in culture aloe-emodin has been shown to dose-dependently inhibit inducible nitric oxide synthase (iNOS) mRNA expression and nitric oxide (NO) production. In addition, cyclooxygenase-2 (COX-2) mRNA and prostaglandin E2 (PGE2) production are suppressed by aloe-emodin. Aloin also suppresses the production of NO but was not shown to suppress PGE2 production. Thus, aloin and aloe-emodin possibly suppress inflammatory responses by blocking iNOS and COX-2 mRNA expression. These anti-inflammatory effects of aloe-emodin were shown to be comparable to that of kaempferol and quercetin (see the Antioxidants page), indicating that aloe-emodin is likely the key compound responsible for the anti-inflammatory activity of aloe.

In studies involving oral administration of aloe vera to mice it was shown to be effective on wound healing, and decreasing the number and size of papillomas and reduce the incidence of tumors and leishmania parasitemia by >90% in the liver, spleen, and bone marrow. Topical application of aloe vera has not been shown to be an effective prevention for radiation-induced injuries and has no sunburn or suntan protection. It can be effective for genital herpes, psoriasis, human papilloma virus, seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus, frostbite, burn, wound healing and inflammation. It can also be used as a biological vehicle and an anti-microbial and antifungal agent and also as a candidate for photodynamic therapy of some kinds of cancer. Even though there have been some promising results with the use of aloe vera for diverse dermatologic conditions, clinical effectiveness of oral and topical aloe vera has not been sufficiently nor meticulously explored in humans as yet.

Chen RS, Jhan JY, Su YJ, Lee WT, Cheng CM, Ciou SC, Lin ST, Chuang SM, Ko JC, and Lin YW 2009. Emodin enhances gefitinib-induced cytotoxicity via Rad51 downregulation and ERK1/2 inactivation. Exp. Cell Res. 315(15):2658-2672.

Park MY, Kwon HJ, and Sung MK 2009. Evaluation of aloin and aloe-emodin as anti-inflammatory agents in aloe by using murine macrophages. Biosci. Biotechnol. Biochem. 73(4):828-832.

Ulbricht C, Armstrong J, Basch E, Basch S, Bent S, Dacey C, Dalton S, Foppa I, Giese N, Hammerness P, Kirkwood C, Sollars D, Tanguay-Colucci S, and Weissner 2007. An evidence-based systematic review of Aloe vera by the natural standard research collaboration. J. Herb. Pharmacother. 7(3-4):279-323.

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Ashwagandha (Withania somnifera): Ashwagandha is a shrub that is found in abundance in India and North America. Ashwagandha is often referred to as Indian ginseng. Consumption of the leaves and roots of the plant are purported to be associated with anti-inflammatory action, promotion of overall wellbeing, and improvement in memory. Ashwagandha extracts have been purported to be beneficial in the treatment of various central nervous system disorders, particularly epilepsy, stress and neurodegenerative diseases such as Parkinson and Alzheimer disease, tardive dyskinesia, cerebral ischemia, and even in the management of drug addiction. The major chemical constituents of the plant genus Withania, are the withanolides which are a group of naturally occurring C28-steroidal lactone triterpenoids built on an intact or rearranged ergostane framework. Analysis of the levels of phenolic compounds and flavonoids in ashwagandha indicates that the concentration of these compounds is approximately 4-5 times higher in the roots than in the leaves.

Treatment of diabetic rats with ashwagandha extracts indicated they were as effective as the diabetes drug glibenclamide (also known as glyburide and sold as Glynase®, Diabeta®, and Micronase®) at reducing blood glucose and increasing glycogen stores (the polymeric form of glucose stored in cells) as well as increasing the levels of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase.

Root extracts from ashwagandha, given orally to mice, were able to increase brain levels of neurotransmitters of the catecholamine family (e.g. dopamine) suggesting that these extracts may be useful in ameliorating some of the effects of Parkinson disease as well as some of the behavioral effects of Huntington disease. In humans ashwagandha has been used to stabilize mood in patients with behavioral disturbances. Several studies have been undertaken to assess the anxiolytic (anti-anxiety) and antidepressant actions of the bioactive withanolides found in root extracts from plants of the Withania genus. In studies in rats ashwagnadha extracts have been shown to induce an anxiolytic effect comparable to that produced by lorazepam (Ativan®). In addition ashwagandha extracts and lorazepam, reduced rat brain levels of tribulin, an endocoid marker of clinical anxiety. Ashwagandha extracts also exhibited an antidepressant effect in this animal study that was comparable with that induced by imipramine (Tofranil®, Deprinol® and others), a member of the tri-cyclic antidepressant family of drugs.

Udayakumar R, Kasthurirengan S, Vasudevan A, Mariashibu TS, Rayan JJ, Choi CW, Ganapathi A, and Kim SC 2010. Antioxidant Effect of Dietary Supplement Withania somnifera L. Reduce Blood Glucose Levels in Alloxan-Induced Diabetic Rats. Plant Foods Hum. Nutr. Feb 26 Epub ahead of print

RajaSankar S, Manivasagam T, Sankar V, Prakash S, Muthusamy R, Krishnamurti A, and Surendran S 2009. Withania somnifera root extract improves catecholamines and physiological abnormalities seen in a Parkinson's disease model mouse. J. Ethnopharmacol. 125(3):369-373.

Kumar P, and Kumar A 2009. Possible neuroprotective effect of Withania somnifera root extract against 3-nitropropionic acid-induced behavioral, biochemical, and mitochondrial dysfunction in an animal model of Huntington's disease. J. Med. Food. 12(3):591-600.

Rajasankar S, Manivasagam T, and Surendran S 2009. Ashwagandha leaf extract: a potential agent in treating oxidative damage and physiological abnormalities seen in a mouse model of Parkinson's disease. Neurosci. Lett. 454(1):11-15.

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Astragalus (Astragalus mongholicus, A. membranaceus): Astragalus is a large genus of about 2,000 species of herbs and small shrubs that belong to the legume family Fabaceae. Astragalus is also known as Milk-Vetch and Huang-qi. Astragalus membranaceus (also known as A. propinquus) has been used as an herbal medicine in China for thousands of years. The herbal medicine is sold primarily as a powder made from the dried root of the astragalus plant and the powder is made into a tea or added to other liquids such as soup to obtain the desired effects. The bioactive compounds present in astragalus are referred to as saponins. Saponins are composed of sugar molecule(s) and a triterpene aglycone molecule. The term aglycone refers to the non-sugar portion of a complex compound. Triterpenes consist of six isoprene units (see The Medical Biochemistry Page for structure of a typical isoprene unit). These bioactive extracts from astragalus are astragalosides and are sometimes referred to as astragalus polysaccharides (APS). The sugars found in APS are arabinose, glucose, and rhamnose. Another bioactive compound found in A. mongholicus is the antioxidant polyphenolic compound genistein. Genistein is a member of the isoflavone class of polyphenols.

The biotechnology companies Geron Corporation and TA Therapeutics of Hong Kong have been working on deriving a telomerase activator from extracts of astragalus. Telomerase is an enzyme required for ensuring that the ends of chromosomes are properly extended during cell division. The progressive shortening of the telomeric ends of our chromosomes during subsequent cell divisions is thought to serve as a biological clock. When the telomeres reach a certain length programmed cell death is triggered. Thus, it is thought that increasing the activity of telomerase will result in a longer life span for cells and a reduction in the progressive process of aging. The astragalus extract, called TAT2, is being developed to be used to help combat HIV, as well as infections associated with chronic diseases or aging. TAT2 is the compound cycloastragenol which is the aglycone  of astragaloside IV found in astragalus and is the smallest molecule in the family of telomerase-activating astragalosides. RevGenetics currently sells a dietary supplement containing astragalus-derived cycloastragenol.

The anti-inflammatory activity of astragalus extracts has been studied using mouse macrophages in culture. Astragalus extracts showed no direct effect on stimulation of mouse macrophages but were able to affect production of tumor necrosis factor-alpha (TNF-α) when used in high concentrations. However, astragalus extract was able to modify inflammatory responses from lipopolysaccharide (LPS)-stimulated macrophages. Treatment of LPS-stimulated macrophages with astragalus resulted in a reduction in the level of TNF-α, interleukin (IL)-6, IL-10, and IL-12 production in a dose-dependent manner. The results demonstrate that astragalus can modulate macrophage responses during stimulation. Therefore, it is hypothesized that their historical use as therapeutic agents may be due to reduction in the pro-inflammatory response that indirectly leads to limiting of clinical symptoms during infection.

Clement-Kruzel S, Hwang SA, Kruzel MC, Dasgupta A, and Actor JK 2008. Immune modulation of macrophage pro-inflammatory response by goldenseal and Astragalus extracts. J. Med. Food 11(3):493-498.

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Bacopa monnieri (Brahmi): A genus of erect or spreading herbs, commonly growing in marshy places throughout India. The entire plant constitutes the well-known drug Brahmi. The leaves are also useful as a diuretic and aperients (laxatives). Dried, whole herb or herb without roots or only leaves and tender stem portions are available as a crude drug formulation. It is astringent, bitter and cooling, and is reported to improve the intellect. It is used for the treatment of asthma, hoarseness, insanity, epilepsy and as a potent nerve tonic, cardio tonic and diuretic. The juice of the leaves is given to children for relief in bronchitis and diarrhea. The paste of the leaves is used as a remedy for rheumatism. In Ayurvedic medicine, the plant is used for dermatitis, anemia and diabetes. It is also used in the treatment of boils and as blood purifier, as a brain tonic to sharpen dull memory, and to treat cataracts. It also has been used to give relief to patients suffering anxiety. The juice, along with ginger juice, sugar and bark extract of Moringa oleifera is given to children to treat stomach disorders.

The herb contains the alkaloids brahmine, herpestatine, and a mixture of three bases. Brahmine is highly toxic and when administered at a dose of 0.5 mg/kg body weight it produces a fall in blood pressure. In therapeutic doses it resembles strychnine. The herb also contains saponins, monnierin, hersaponin, bacoside-A and bacoside–B. Monnierin, on hydrolysis, yields glucose, arabinose and aglycone whereas, bacosides A and B yield glucose, arabinose and bacogenines A, A2, A3 and A4. Bacogenines A1 and A2 are epimers, and A4 is an ebelin lactone. Degradation of bacoside A yields jujubogenin and pseudojujubogenin. Bacosides A and B possess haemolytic activity. Other constituents present in the plant are D-mannitol, betulic acid, β-sitosterol, stigma-sterol and its esters, heptacosine, octacosane nonacosane, triacontane, hentriacontane, dotriacontane, nicotine, 3-formyl-4-hydroxy-2H-pyran, luteolin and its 7-glucoside.

Morgan, A and Stevens, J 2010. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. J Compliment. Altern. Med. 16(7):753-759

Shinomol GK, Mythri RB, Srinivas Bharath MM, and Muralidhara 2011 Bacopa monnieri Extract Offsets Rotenone-Induced Cytotoxicity in Dopaminergic Cells and Oxidative Impairments in Mice Brain Cell. Mol. Neurobiol. ePub ahead of print December 10

Jadiya P, Khan A, Sammi SR, Kaur S, Mir SS, and Nazir A 2011 Anti-Parkinsonian effects of Bacopa monnieri: insights from transgenic and pharmacological Caenorhabditis elegans models of Parkinson's disease. Biochem. Biophys. Res. Commun. 413(4):605-610

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Bilberry (Vaccinium myrtillus L.): Although there are numerous types of bilberries, all of the genus Vaccinium, the most commonly used for dietary supplementation is Vaccinium myrtillus which is the European blueberry. The dried fruit of bilberry has been used for the symptomatic treatment of diarrhea, for topical relief of minor mucus membrane inflammation, and for a variety of eye disorders, including poor night vision, eyestrain, and myopia. The extracts of bilberry fruit contain a number of biologically active components, including polyphenolic antioxidant compounds called anthocyanins (specifically anthocyanosides) and numerous flavonoids. Bilberry extract has been evaluated for efficacy as an antioxidant, mucostimulant, hypoglycemic, anti-inflammatory, vasoprotectant, and lipid-lowering agent. Although pre-clinical studies have been promising, human data are limited and largely of poor quality. There is currently no sufficient evidence in support of (or against) the use of bilberry for most indications. Notably, the evidence suggests a lack of benefit of bilberry for the improvement of night vision.

In an analysis of genes whose expression levels were affected by treatment of human macrophage cell lines with bilberry extracts there were 308 genes identified and classified into 43 categories relating to biological processes (97), molecular functions (186), and signaling pathways (26). Each of the identified genes exhibited at least a >1.5-fold change. Genes that are categorized as defense, inflammatory response, cytokines activities, and receptor activities were further classified. The results of this DNA microarray study provide a molecular basis for the anti-inflammatory effects of bilberry.

Bilberry extracts are also effective as cytotoxic agents resulting the killing of cancer cells, such as breast cancer, in culture. Bilberry extracts inhibit cell proliferation in a concentration-dependent fashion (50% inhibition with 0.3–0.4mg/ml) in concert with induction of apoptotic cell death. At higher extract concentrations (0.5–0.9 mg/mL) the extracts resulted in an increase in the fraction of cells blocked at the point in the cell cycle just prior to cell division, together with destruction of microtubules. These data suggest that bilberry extract as ingested by humans, not just the purified anthocyanins it contains, can inhibit proliferation of and induce apoptosis in breast cancer cells.

Nguyen V, Tang J, Oroudjev E, Lee CJ, Marasigan C, Wilson L, and Ayoub G 2010. Cytotoxic effects of bilberry extract on MCF7-GFP-tubulin breast cancer cells. J. Med. Food 13(2):278-285.

Chen J, Uto T, Tanigawa S, Kumamoto T, Fujii M, and Hou DX 2008. Expression profiling of genes targeted by bilberry (Vaccinium myrtillus) in macrophages through DNA microarray. Nutr Cancer. 60 Suppl 1:43-50.

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Black cohosh (Actaea racemosa): Black cohosh is a member of the buttercup family of plants and is native to North America. Dietary supplements made from black cohosh are comprised of extracts from the roots and rhizomes (the horizontal stem of a plant found underground: picture the ginger root you find in the grocery store). The primary use for black cohosh is as an alternative medical treatment for hot flashes and other menstrual discomforts.

Remifemin is a commercially available standardized tablet preparation of black cohosh extract. The primary bioactive compound in black cohosh is 26-deoxyacetin, member of the saponin family of chemicals (natural detergents found in plants). Black cohosh was used by North American Indians for treating malaise, rheumatism, colds, coughs, constipation, kidney ailments, hives, backache, and to induce labor. Few controlled studies have been carried out to assess the biological activity of black cohosh in humans. One double-blinded study of black cohosh (given as two 2mg tablets of Remifemin twice daily) demonstrated that hot flashes were reduced in intensity and frequency in menopausal women.

Unfortunately, many studies on the effects of black cohosh have yielded conflicting results. At least 4 case studies have reported possible hepatotoxicity with black cohosh consumption, although previous safety reviews suggest that black cohosh is well tolerated and that adverse events are rare when it is used appropriately.

Shams T, Setia MS, Hemmings R, McCusker J, Sewitch M, and Ciampi A 2009. Efficacy of black cohosh-containing preparations on menopausal symptoms: a meta-analysis. Altern. Ther. Health Med. 16(1):36-44.

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Boswellia (Boswellia serrata): Boswellia serrata is commonly known as Indian frankincense or Salai. A gum resin extract of the tree has been used in traditional Ayurvedic medicine for hundreds of years in the treatment of arthritis. In the Ayurvedic tradition of medicine, any resin that is collected by tapping the trunk of a tree is called guggul (or guggal). Many different trees of Indian have resin extracts used in Ayurvedic medical treatments (see below for example). The gum resin extracts of Boswellia contain volatile oils and boswellic acids, the latter constituting approximately30% of the extracts components. Boswellic acids are pentacyclic triterpenes, which may exist in an α-configuration (geminal methyl groups at C-20) or a β-configuration (vicinal methyl groups at C-19/C-20). Furthermore, boswellic acids may contain an oxo-moiety at C-11 and an acetyl moiety at the C-3 OH group. Various pharmacological studies indicate that β-configuration derivatives exert stronger bioactivities as compared to the respective α-isomers. The gum resins from different Boswellia species vary in their boswellic acid composition. This fact is one of the difficulties with assessing the clinical significances of Boswellia. Many different B. serrata products with differing composition have been subject to clinical investigations. Frequently, the methods used to obtain the gum resin extracts, as well as the composition of the extracts is not disclosed further complicating clinical evaluations. Nonetheless, several studies in animals and humans are highlighted below.

Boswellia extracts have also been used traditionally to treat arthritis, ulcerative colitis, coughs, sores, snakebite, and asthma. The major bioactive component of Boswellia extracts is boswellic acid, which was shown in animal studies to be a potent 5-lipoxygenase (5-LOX) inhibitor with anti-inflammatory and antiarthritic effects. For more information on the activities of 5-LOX please visit The Medical Biochemistry Page. When tested in humans boswellic acid appears to have fewer adverse effects than steroids and non-steroidal anti-inflammatory (NSAIDs) drugs. However, its long-term effects on humans are currently unknown. Because boswellic acid is contained in a typical Ayurvedic guggul extract it can thus, be considered a guggul but it should not be confused with guggul or myrrh. The latter extracts represent the guggul extracted from the Mukul myrrh tree of India (see the guggul discussion below).

Given the observed ability of Boswellia extracts to inhibit 5-LOX and thus, impart anti-inflammatory effects, a novel formulation has been generated and is referred to as 5-Loxin. This Boswellia extract is enriched in two forms of boswellic acid (11-keto-β-boswellic acid, KBA: 3-O-acetyl-11-keto-β-boswellic acid, AKBA) and has been tested for efficacy in the treatment of osteoarthritis. Patients in this trial were given two different doses of 5-Loxin once daily for 90 days and then monitored for pain and range of movement of their osteoarthritic knees. Both doses of 5-Loxin conferred clinically and statistically significant improvements in pain scores and physical function scores in the test patients. Of significance there were observable improvements in pain score and functional ability in the treatment group supplemented with the higher dose (250mg) of 5-Loxin as early as 7 days after the start of treatment. In addition to the improvements in pain scores in treatment groups, it was also noted that there was a significant reduction in synovial fluid matrix metalloproteinase-3 (MMP-3). The results of this study indicate that 5-Loxin reduces pain and improves physical functioning significantly in osteoarthritic patients and is safe for human consumption. 5-Loxin likely exerts its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators, and it may improve joint health by reducing the enzymatic degradation of cartilage.

However, results from recent human studies have questioned the pharmacological relevance of 5-LOX inhibition by 11-keto boswellic acids (KBA and AKBA), since neither any boswellic acid nor Boswellia extract caused significant inhibition of 5-LOX in a physiologically relevant assay (human whole-blood assay), and oral intake of Boswellia extract failed to reduce leukotriene-B4 (LTB4) levels in human test subjects. Following oral administration of Boswellia extract, only very low steady-state concentrations of KBA and AKBA in plasma (<0.33 and <0.1 mmol/L, respectively) were observed, whereas 100-fold higher levels were evident for β-boswellic acid which inhibits microsomal prostaglandin E synthase-1 and the serine protease cathepsin G. Thus, these two enzymes might be reasonable molecular targets related to the anti-inflammatory properties of Boswellia serrata extracts.

Since extracts from Boswellia have been shown to exhibit anti-inflammatory activities varies studies have been undertaken to assess the mechanism of action. In one study a crude methanolic extract as well as a purified compound (12-ursene 2-diketone) from the extract were analyzed for their inhibitory effect on tumor necrosis factor-alpha (TNFα), interleukin-1beta (IL-1β) and IL-6 when added to cultures of immortalized mouse macrophage cells as well as human peripheral blood mononuclear leukocytes (PBMCs). Results of theses studies demonstrated that all three cytokines are down regulated when cells are cultured in the presence of crude extract or 12-ursene 2-diketone at various time points. The extract and 12-ursene 2-diketone also showed considerable inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse macrophages, possibly via suppression of inducible NO synthase (iNOS) mRNA expression. These results demonstrated that 12-ursene 2-diketone inhibits the expression of pro-inflammatory cytokines and mediators via inhibition of phosphorylation of the mitogen-activated protein kinases (MAPKs) Jun N-terminal kinase (JNK) and p38MAPK while no inhibition was seen in ERK phosphorylation in LPS-stimulated PBMCs. The study results indicate that the crude methanolic extract and 12-ursene 2-diketone are capable of carrying out a natural anti-inflammatory activity at sites where chronic inflammation is present by switching off the pro-inflammatory cytokines and mediators, which initiate the process.

Boswellic acid has also been tested for its efficacy in treating the clinical manifestations of photoaging of the facial skin. A cream containing 0.5% boswellic acid was tested on 15 females by application once daily for 30 days. In this study there was a statistically significant measureable change in tactile roughness and fine lines on the side of the face treated with the boswellic acid containing cream compared to the side of the face treated with the same cream lacking boswellic acid.

Abdel-Tawab M, Werz O, and Schubert-Zsilavecz M 2011. Boswellia serrata: An Overall Assessment of In Vitro, Preclinical, Pharmacokinetic and Clinical Data. Clin. Pharmacokinet. 50(6):349-369

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Cascara sagrada (Rhamnus purshiana): Cascara sagrada (Spanish for sacred bark) comes from the American buckthorn tree native to the western coast of North America. The much more pertinent name chittam or chitticum literally means "shit come" from Chinook Indian jargon. The bark of this plant has been used by North American Indians as a laxative, hence the slang name for the herbal remedy.

One important chemical found in the rhizomes of Rhamnus purshiana (as well as rhubarb and numerous other plants) is the anthraquinone emodin. Emodin (chemical name: 1,3,8-trihydroxy-6-methyl-anthraquinone) has been reported to suppress tumor growth in many clinical situations. This activity of emodin is the result of its action as a tyrosine kinase inhibitor and many growth factor receptors have intrinsic tyrosine kinase activity. The anti-cancer drug getfitinib (Iressa®), which itself is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for human non-small cell lung cancer (NSCLC), together with emodin resulted in enhanced cytotoxicity in NSCLC cells in culture. These results suggest that emodin-getfitinib co-treatment may serve as the basis for a novel and more effective therapy in the management of advanced lung cancer.

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Chamomile (Matricaria recutita): Chamomile belongs to a family of daisy-like plants and is best known for its use in the making of tea. Chamomile tea contains a chemical compound called chrysin which is an isoflavone (a member of the flavonoid family of antioxidants) with the chemical name 5,7-dihydroxyflavone. Chrysin has been shown to induce calm (referred to medically as an anxiolytic, i.e. relieving anxiety) in laboratory animals. This likely explains the use of chamomile tea as a sleep aid.

Chrysin was shown to inhibit the enzyme aromatase in cells in culture. Aromatase is the enzyme responsible for the conversion of androstenedione to estrone and testosterone to estradiol. These reactions are responsible for converting androgens (male sex hormones) to estrogens (female sex hormones). Aromatase inhibitors (e.g. anastrozole) were developed as chemotherapeutics designed to inhibit estrogen production in breast cancer patients, thereby inhibiting the growth of the cancer. Because of the effects of chrysin on the activity of aromatase it was touted as an herbal remedy to increase testosterone in males. However, there is no clinical evidence to demonstrate that chamomile tea or chrysin itself when ingested leads to increased testosterone production. This is due to the low bioavailability of chrysin following oral consumption.

Lipid extracts of chamomile also contain apigenin-7-O-glucoside. The lipid fraction isolated from chamomile flowers exhibits a higher biologic response in inhibiting cell growth and causing induction of apoptosis in various human cancer cell lines than compared to the aqueous fraction of the flowers. Apigenin glucosides inhibited cancer cell growth but to a lesser extent than the parent aglycone, apigenin. The aglycone is produced within the cells following uptake explaining the growth inhibiting action on cells.

Chamomile also contains coumarin, a naturally-occurring compound with anticoagulant or blood-thinning effects. Coumarins (chemical structures are benzopyrenes) are present in numerous plants and they act as vasodilators and anti-fungals in humans. Coumarin components should not be used in conjunction with other blood thinners such as warfarin or aspirin as excessive bleeding may result.

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Chinese Tonic Soup Herbs: The Chinese medicated diet consists of, among many things, numerous tonic soups made from various herbs. Many of these herbs have been tested for levels of antioxidants and this research has confirmed that drinking tonic soups could supplement total antioxidant intake. Some of these herbs for preparing tonic soups are listed in the following Table.

Latin Name Common Name Plant Family Herbal Part
Alpinia officinarum Rhizome alpiniae officinari Zingiberaceae root
Angelica sinensis Chinese angelica Apiaceae root
Astragalus membranaceus Milk-vetch or Huang-qi Fabaceae root
Canarium album Fruit of white canarium
(Chinese white olive)
Burseraceae fruit
Cistanche deserticola Desertliving cistanche Orobanchaceae stem
Eucommia ulmoides Eucommia Eucommiaceae bark
Flos caryophylli Eugenia caryophylata Thunb
Myrtaceae flower
Fructus amomi Fruit of Villous Amomum Zingiberaceae fruit
Glycyrrhiza uralensis Licorice Fabaceae root
Illicium verum Truestar anisetree Illiciaceae fruit
Ligustrum lucidum Glossy Privet Oleaceae fruit
Lycium barbarum Barbary Wolfberry Solanaceae fruit
Polygonatum odoratum Fragrant Solomonseal Liliaceae root
Polygonatum sibircum Solomonseal Liliaceae rootstalk
Rehmannia glutinosa Adhesive Rehmannia Scrophulariaceae root
Ziziphus jujuba Spine Date Rhamnaceae fruit

Among the herbal tonics listed in the Table above, extracts of Canarium album Raeusch., Flos caryophylli and Fructus amomi have been shown to have the highest antioxidant activities. Their antioxidant activities have been shown to be comparable to that of vitamin C (ascorbic acid). Studies examining the antioxidant activity of these various herbs indicate that they are safe and inexpensive sources of natural antioxidants. In analyzing these herbal tonics it has been found that a significant relationship exists between their antioxidant effects and the total concentration of polyphenolic compounds, thus indicating their phenolic compounds are the major contributor of antioxidant capacities of these herbs. In addition, the antioxidants in these herbs are capable of scavenging free radicals and reducing oxidants.

Extracts from C. album have been shown to have anti-hepatotoxic activity in primary cultured rat hepatocytes and possess protective effect against xenobiotic-induced liver damage in mice. Both in vitro and in vivo hepatoprotective activities of C. album are likely due to their antioxidant effects and high phenolic contents. The major antioxidant and free radical scavenging compounds in this plant are scoparone, scopoletin, (E)-3,3'-dihydroxy-4,4'-dimethoxystilbene and gallic acid.

F. amomi is traditionally used to cure digestive tract disease and stimulate to the appetite in China. The major non-volatile compounds isolated from the herb are β-sitosterol, vanillic acid, stearic acid and palmitic acid. The main volatile components are bornyl acetate, camphor, borneol, limonene, camphene, myrecene, carene-3 and α-terpeneol. Some of these compounds could be antioxidants.

The antioxidant effect of A. officinarum can be explained by the presence of phenylpropanoids and glycosides, such as β-glycosides of chavicol and 1,2-dihydroxy- 4-allylbenzene, which contains phenolic hydroxyl groups in the molecule.

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Cinnamon (Cinnamomum verum, C. zeylanicum, and C. cassia): The primary sources of cinnamon come from the Ceylon cinnamon (considered true cinnamon) and the Cassia cinnamon. The vast majority of cinnamon sold in North America comes from the less expensive Cassia cinnamon. Although not classically considered an herbal supplement, a discussion of cinnamon is included here since several other herbal supplements can be prepared as a spice (e.g. turmeric). Cinnamon is normally found as dried sticks prepared from the bark of the cinnamon tree or the bark is ground into a fine powder for use as a spice.

Cinnamon has extremely high antioxidant, antibacterial and antifungal properties. The use of cinnamon as an alternative medicine has been touted for the treatment of diarrhea, toothaches, headaches, and migraines, as well as a digestion aid, for the reduction of cholesterol levels, treatment of arthritis pain, and boosting memory.

Cinnamon has been reported to be effective in the alleviation of diabetes through its antioxidant and insulin-potentiating activities. Several phenolic compounds, such as catechin, epicatechin, and procyanidin B2, and phenol polymers have been identified in aqueous subfractions of cinnamon extracts. These compounds have significant inhibitory action on the formation of glycoslyated proteins (termed advanced glycation endproducts, AGEs). In humans the principal AGE found in the blood of diabetics is glycosylated hemoglobin identified as HbA1c (clinically more common to report as A1c level).

One additional bioactive compound found in cinnamon is cinnamaldehyde, CND (chemical name is 3-phenyl-2-propenal). This compound has also been shown to have beneficial effects on the symptoms of diabetes in experimental animal models of the disease. Oral administration of 20 milligrams per gram of body weight (mg/kgbw) of cinnamaldehyde to diabetic rats for 2 months showed significant improvement in muscle and hepatic glycogen content. In vitro incubation of pancreatic islets with CND enhanced the insulin release compared to glibenclamide. Glibenclamide is a sulphonylurea class of diabetes drug which is the generic name for Glyburide® and Glynase®. The insulinotropic effect of CND was found to increase glucose uptake through glucose transporter (GLUT4) translocation in peripheral tissues. The treatment also showed a significant improvement in altered enzyme activities of pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK) and their mRNA expression levels. Of significance for the use of cinnamaldehyde as a therapeutic for type 2 diabetes, the median lethal dose of CND could not be obtained even at 20 times (0.4g/kgbw) of its effective dose in these laboratory rats. Thus, with the high margin of safety of CND, it can be developed as a potential therapeutic candidate for the treatment of diabetes. Ingestion of cassia cinnamon has indeed been shown to facilitate glucose disposal in healthy humans. This effect of cinnamon in humans is thought to be the result of enhancing insulin sensitivity via increased phosphorylation of signaling proteins and insulin-sensitive glucose transporter 4-mediated (GLUT4) glucose uptake into muscle cells.

Anand P, Murali KY, Tandon V, Murthy PS, and Chandra R 2010. Insulinotropic effect of cinnamaldehyde on transcriptional regulation of pyruvate kinase, phosphoenolpyruvate carboxykinase, and GLUT4 translocation in experimental diabetic rats. Chem. Biol. Interact. Apr 2 Epub ahead of print.

Peng X, Cheng KW, Ma J, Chen B, Ho CT, Lo C, Chen F, and Wang M 2008. Cinnamon bark proanthocyanidins as reactive carbonyl scavengers to prevent the formation of advanced glycation endproducts. J. Agric. Food Chem. 56(6):1907-1911.

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Clary sage (Salvia sclarea): Clary sage has been used as an herbal tonic for thousands of years to treat infertility and digestive problems as well as for use as a sedative. The essential oil extracted from Clary sage is used in aromatherapy, and for its purported antidepressive and antibacterial activities. The major active ingredient in the essential oil of Clary sage is the labdane diterpene sclareol (labd-14-ene-8,13-diol). The labdane class of chemicals is so-called because the original compound was isolated from labdanum which is a sticky resin obtained from Cistus ladanifer and Cistus creticus (commonly known as rockrose). Sclareol is used as a fragrance in cosmetics and perfumes and as flavoring in food. Sclareol has been shown to have the ability to induce apoptosis (programmed cell death) in cultures of human leukemic cells and colon cancer cells. In addition, sclareol has been shown to reduce breast cancer tumor growth in vivo. The antibacterial activity of sclareol has been demonstrated against several organisms including Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis.

Noori S, Hassan ZM, Mohammadi M, Habibi Z, Sohrabi N, and Bayanolhagh S. 2010. Sclareol modulates the Treg intra-tumoral infiltrated cell and inhibits tumor growth in vivo. Cell Immunol. 263(2):148-153.

Dimas K, Hatziantoniou S, Tseleni S, Khan H, Georgopoulos A, Alevizopoulos K, Wyche JH, Pantazis P, and Demetzos C. 2007. Sclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in immunodeficient mice. Apoptosis 2007 12(4):685-694.

Hayet E, Fatma B, Souhir I, Waheb FA, Abderaouf K, Mahjoub A, and Maha M. 2007. Antibacterial and cytotoxic activity of the acetone extract of the flowers of Salvia sclarea and some natural products. Pak. J. Pharm. Sci. 20(2):146-148.

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Cnidium monnieri: The fruit of Cnidium monnieri is a Chinese herbal medicine and has been used in clinics for many years. Cnidium has many purported functions including acting as an anti-inflammatory, preventing osteoporosis and as a anti-tumor agent. Several herbal supplement preparations marketed for their purported ability to aid erectile dysfunction contain Cnidium extracts. Cnidium seeds contain several compounds including osthole (a coumarin-related conmpound also spelled osthol), xanthotoxol, imperatorin, bergapten, monoterpene polyols, glucides and hepatoprotective sesquiterpenes. Osthole (chemical name 7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one) is the predominant bioactive compound found in Cnidium extracts and is the compound shown in several studies to be responsible for the anti-tumor activity and for preventing osteoporosis.

Anti-tumor studies using osthole have demonstrated that the compound has potential in the treatment HER2-overexpressing breast cancers (HER2 is a gene that expresses a growth factor receptor protein). Expression of one of the enzymes involved in the synthesis of fatty acids within cells (fatty acid synthase, FAS) has been shown to be expressed in many human solid tumors in pre-neoplastic lesions. HER2, expressed in pre-neoplastic breast lesions, has been shown to up-regulate the expression of FAS. Osthole has been shown to be effective in suppressing FAS expression in HER2-overexpressing breast cells. In these studies, the addition of osthole to HER2-overexpressing cancer cells showed that the compound exhibits a preferential inhibition of proliferation and an induction of apoptosis in these cells. An additionally important finding from the study of osthole effects in HER2-overexpressing breast cancer cells is that osthole could enhance paclitaxel (Taxol®)-induced cytotoxicity in these cells. The results of this study suggest that osthole has the potential to function as a chemopreventive or chemotherapeutic agent for cancers that overexpress HER2.

Osthole has also been shown to have potential in the treatment of hyperglycemia in type 2 diabetes patients. To investigate the glucose lowering (hypoglycemic) effects of osthole studies were undertaken using diabetic mice. When added to cells in culture isolated from these diabetic mice osthole significantly activated two genes involved in regulating insulin-mediated effects. These genes are identified as peroxisome proliferator-activated receptor (PPAR) alpha and gamma (PPARα and PPARγ). The activation of PPARα and PPARγ by osthole also resulted in an increase in the expression of PPAR target genes such as PPAR itself, adipose fatty acid-binding protein 2 (involved in the release of fatty acids stored in adipose tissue), acyl-CoA synthetases (enzymes necessary to activate fatty acids for metabolism), and carnitine palmitoyltransferase-1 (involved in metabolism of fatty acids for production of cellular energy). The cell-based studies suggest that osthole might be a dual PPARα/γ activator, but its chemical structure differs from that of the thiazolidinedione (TZD) class of antidiabetic drugs (for more information of antidiabetic drugs such as the TZD class visit The Medical Biochemistry Page). Additional activities associated with osthole identified in this study are a significant activation the AMP-activated protein kinase (AMPK) which is a master metabolic regulator within cells. When obese diabetic mice are treated with osthole it has been found that osthole markedly reduces blood glucose level. Interestingly, osthole did not reduce the level of insulin or serum lipid levels in this study whereas, this does occur in animals treated with insulin sensitizers like the TZD class of PPAR agonists. The results of this study indicate that osthole can alleviate hyperglycemia and could be potentially developed into a novel drug for treatment of diabetes.

Liang HJ, Suk FM, Wang CK, Hung LF, Liu DZ, Chen NQ, Chen YC, Chang CC, and Liang YC 2009. Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice. Chem. Biol. Interact. 181(3):309-315.

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Coleus forskohlii: Coleus forskohlii is a member of the mint and lavender family which grows in the mountains of Asia. The primary active chemical found in this herbal medicine is a labdane diterpene called forskolin (chemical name 7β-acetoxy-8, 13-epoxy-1α,6β,9α-trihydroxy-labd-14-en-11-one). The labdane class of chemicals is so-called because the original compound was isolated from labdanum which is a sticky resin obtained from Cistus ladanifer and Cistus creticus (commonly known as rockrose).

Forskolin has been studied in the laboratory for many years due to its ability to increase the level of the second messenger molecule, cyclic adenosine monophosphate (cyclic AMP, cAMP) in cells in culture. Intracellular production of cAMP results in the activation of an enzyme called cAMP-dependent protein kinase. Kinases are enzymes that incorporate phosphate onto their substrates which results in altered activity of the phosphorylated substrate. For more information on the role of cAMP in metabolism visit The Medical Biochemistry Page. As an Ayurvedic medicine Coleus forskohlii has been used in the treatment of allergies, respiratory problems, cardiovascular diseases, glaucoma, psoriasis, hypothyroidism and weight loss.

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Comfrey, comfry (Symphytum officinale): Comfrey is a perennial shrub that is native to Europe and temperate parts of Asia. Comfrey is used to treat wounds and reduce the inflammation associated with sprains and broken bones. Comfrey preparations are made from the leaves or other parts of the plant grown above the ground. Comfrey contains substances that help skin regenerate, including allantoin, rosmarinic acid, and tannins.

Allantoin (chemical name: 5-ureidohydantoin or glyoxyldiureide) is named after the allantois, an embryonic excretory organ in which allantoin concentrates during development in most mammals. Allantoin is a product of the oxidation of uric acid which is itself a byproduct of the catabolism of nucleic acids found in DNA and RNA. Allantoin is a compound that has been shown to help new skin cells grow.

Historically, comfrey ointments were often applied to the surface of the skin to heal bruises as well as pulled muscles and ligaments, fractures, sprains, strains, and osteoarthritis. Comfrey also contains poisonous compounds called pyrrolizidine alkaloids. The roots of the comfrey plant contain up to 16 times more pyrrolizidine alkaloids than the leaves. For this reason it is recommended that one only use topical preparations that are made from the leaves. Because of the presence of these toxic compounds oral comfrey products have been banned in the U.S. and many European countries.

One recent clinically controlled study has demonstrated a high degree of efficacy for topical application of comfrey root extract in treating acute upper and lower back pain. Trial participants were treated with comfrey ointment (4 gm per treatment) three times per day for 5 days. The results of this study showed that comfrey root extract demonstrated a remarkably potent and clinically relevant effect in reducing acute back pain.

The effects of oral comfrey extracts have been studied in laboratory animals for the treatment of hepatic cancer. In these studies, comfrey extract is administered at high doses during several months and the neoplastic hepatic lesions in the animals are evaluated. The efficacy of chronic oral treatment with 10% comfrey ethanolic extracts was assessed in rats induced to develop hepatic carcinomas by pre-treatment with carcinogenic chemicals. The results of the study indicated that the ingestion of the 10% comfrey alcoholic extract reduced hepatic cell proliferation in this model.

Giannetti BM, Staiger C, Bulitta M, and Predel HG 2010. Efficacy and safety of comfrey root extract ointment in the treatment of acute upper or lower back pain: results of a double-blind, randomised, placebo controlled, multicentre trial. Br. J. Sports Med. Apr 19 Epub ahead of print.

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Dong quai (Angelica sinensis): More than 60 species of medicinal plants belong to the genus Angelica (family: Apiaceae). Don quai is also known as Chinese Angelica. This herbal supplement has been used for thousands of years in traditional Chinese, Korean, and Japanese medicine. It is used primarily for health conditions in women which is why it is commonly referred to as "female ginseng".

Coumarin derivatives are thought to be the active ingredients in dong quai. Coumarins (chemical structures are benzopyrenes) are present in numerous plants and they act as vasodilators and anti-fungals in humans. Dong quai is used for painful menstruation or pelvic pain, recovery from childbirth or illness, and fatigue/low vitality. However, clinical trials have yet to support the use of dong quai for improving menopausal symptoms. Various herbal preparations from Angelica species have been used traditionally as anti-inflammatory, diuretic, expectorant and diaphoretic, and remedy for colds, flu, influenza, hepatitis, arthritis, indigestion, coughs, chronic bronchitis, pleurisy, typhoid, headaches, wind, fever, colic, travel sickness, rheumatism, bacterial and fungal infections and diseases of the urinary organs. One active ingredient in dong quai, furanocoumarin bergapten, may have carcinogenic properties. Coumarin components should not be used in conjunction with other blood thinners such as warfarin or aspirin as excessive bleeding may result. Dong quai is not recommended for women with excessive menstrual flow, those with fibroids, or fever.

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Echinacea: Echinacea is a genus of nine species of the Asteraceae family of plants. Echinacea preparations, widely used for the prevention and treatment of upper respiratory tract infections, are prepared from the roots and/or other parts of the plants belonging to several members of the Echinacea family, including E. purpurea, E. angustifolia, and E. pallida. These multiple species have phytochemical similarities, but also have notable differences, particularly around the identity and concentration of alkylamides, which are chemical compounds that can modulate the liver drug metabolizing enzymes of the cytochrome P450 (CYP) family, and caffeic acid derivatives. Many preparations of commercially available echinacea supplements contain extracts from each of the three different species indicated. This fact makes it difficult to assess the comparative effectiveness of various preparations of echinacea.

Preclinical studies indicate that echinacea works through modulation of immune mechanisms. Numerous clinical trials have been carried out on different types of preparations from echinacea and several, but not all, of these clinical trials have reported effects superior to those of placebo in the prevention and treatment of upper respiratory tract infections as well as shortening the duration and severity of colds when taken as soon as symptoms become evident. However, trials of long-term use of echinacea as a preventive have not shown positive results.

A recently released study on the efficacy of the use of echinacea for the treatment of the common cold has found that there is no statistically significant difference in several parameters in comparison of placebo versus echinacea treated patients. In this study several hundred patients ranging in age from 12 to 80 years of age were divided into four treatment groups: no pills, placebo pills (patients were blinded from investigators), echinacea pills (patients were blinded from investigators), and echinacea pills given as unblinded open label medication. The purpose in the latter group was to ascertain whether the expectation of receiving a potentially positive treatment compound would have measurable effects on the outcomes of the patients. The study duration lasted for 4 days and several parameters were measured. Study patients were asked to assess the severity of their symptoms twice daily using the Wisconsin Upper Respiratory Symptom Survey, short version. Secondary study outcomes included measurement of the pro-inflammatory chemokine, interleukin-8 levels as well as neutrophil counts from nasal wash. These latter two paramters are used to assess the level of inflammation. A comparison of the blinded groups showed a nonsignificant 0.53-day difference in the mean illness duration. Median change in interleukin-8 levels and neutrophil counts were also not statistically significant in this study. The conclusions of this study are that echinacea does not lessen the severity nor the duration of the common cold in any statistically significant measure.

Specific effects of echinacea extracts on immune function have not been studied in detail in humans. A recent study aimed at defining the effects of E. purpurea extracts in mouse bone marrow-derived dendritic cells (DCs), which generate innate and adaptive immune responses, was carried out. The fate and function of DCs from C57Bl/6 mice was evaluated following 48hr exposure to E. purpurea root and leaf extracts. The polysaccharide-rich root extract increased the expression of cell surface biomarkers of immune activation whereas the alkylamide-rich leaf extract inhibited expression of these molecules. Production of the inflammatory stimulating proteins IL-6 and TNF-alpha (TNF-α) increased in a concentration-dependent manner with exposure to the root, but not leaf, extract. In contrast, the leaf but not root extract inhibited the enzymatic activity of cyclooxygenase-2 (COX-2). Collectively, these results suggest that E. purpurea can be immunostimulatory, immunosuppressive, and/or anti-inflammatory depending on the portion of the plant and extraction method.

No clinical studies have been published demonstrating adverse interactions between echinacea and other prescription drugs. Although further studies into the interaction potential of this herbal medicine would be useful, the currently available evidence suggests that echinacea is unlikely to pose serious health threats for patients combining it with conventional drugs.

Barrett B, Brown R, Rakel D, Mundt M, Bone K, Barlow S, and Ewers T. 2010 Echinacea for treating the common cold: a randomized trial. Ann. Intern. Med. 153(12):769-777.

Shah SA, Sander S, White CM, Rinaldi M, and Coleman CI 2007. Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis. Lancet Infect. Dis. 7(7):473-480.

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Epimedium (Horny goat weed): Epimedium is a genus of about 60 or more species of herbaceous flowering plants in the family Berberidaceae. Common names for the plant include horny goat weed, rowdy lamb herb, barrenwort, Bishop's hat, fairy wings, or Yin Yang Huo. Several of the varieties of Epimedium are used as herbal supplements such as Epimedium grandiflorum, Epimedium sagittatum, Epimedium brevicornum, Epimedium koreanum, and Epimedium diphyllum, and Epimedium sempervirens. Epimedium containing supplements are purported to enhance libido and increase sexual thoughts, enhance orgasm intensity, and to increase energy and stamina. Several herbal supplement preparations marketed for their purported ability to aid erectile dysfunction contain Epimedium grandiflorum. Results from in vitro studies suggest that components of Epimedium exhibit neuroprotective, immunomodulatory, and anticancer effects.

Extracts from leaves of Epimedium contain flavonoids, sterols, lignans, sesquiterpenes, prenylflavones, phenolic glycosides, and epimedin C. The principal bioactive flavonoid found in Epimedium is icariin. Icariin has been shown to exert inhibitory action in vitro on the enzyme phosphodiesterase-5 (PDE5). PDE5 actually exists in three isoforms due to alternative splicing of the PDE5A gene encoded mRNA. These three isoforms are identified as PDE5a1, 2 and 3. PDE5A1 and PDE5A2 are ubiquitously expressed in all cells while PDE5A3 is specific to smooth muscle. PDE5A isoforms degrade the second messenger signaling compound, cyclic guanosine-monophosphate (cGMP) in smooth muscle cells so as to maintain the contracted state of contractile organs such as the penis, blood vessels, uterus, and intestines. In addition, it regulates numerous other physiological processes such as neurogenesis and apoptosis. PDE5A is best known as the target of the erectile dysfunction (ED) drug sildenafil (Viagra®). There

Rats treated with low-dose icariin showed significantly greater levels of the mRNA encoding neuronal nitric oxide synthase (nNOS) and calponin in penile tissues. Icariin treatment also led to significantly greater neurite length in cultured specimens of pelvic ganglia. Results from studies such as these indicate that icariin may have neurotrophic effects in addition to known PDE5A1 inhibiting effects.

Epimedium has also been studied for its efficacy in the treatment of erectile dysfunction (ED). A relatively new herbal combination supplement marketed for the treatment of ED, called Etana, contains Epimedium. In addition to Epimedium, Etana contains three additional herbal extracts including Panax quinquelotius (Ginseng), Eurycoma longifolia Jack (Tongkat Ali), and Centella asiatica (Gotu Kola). In a study using male rats, the effects of Etana administration were monitored by assessing penile erection, genital grooming and copulation mounting. When compared with sildenafil citrate (Viagra®), Etana induced more pronounced penile erections. It is important to point out that the effects of Etana on erectile function are due to the entire herbal combination since any single herbal supplement alone, or any combination of two of the herbal components of Etana did not produce efficacious results. The results of this study indicate that this is a safe combination of herbal components that enhance erectile function.

Dell'Agli M, Galli GV, Dal Cero E, Belluti F, Matera R, Zironi E, Pagliuca G, and Bosisio E 2008. Potent inhibition of human phosphodiesterase-5 by icariin derivatives. J. Nat. Prod. 71(9):1513-1517.

Shindel AW, Xin ZC, Lin G, Fandel TM, Huang YC, Banie L, Breyer BN, Garcia MM, Lin CS, and Lue TF 2010. Erectogenic and neurotrophic effects of icariin, a purified extract of horny goat weed (Epimedium spp.) in vitro and in vivo. J. Sex Med. 7(4 Pt 1):1518-1528.

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Evening primrose (Oenothera biennis): The use of evening primrose for dietary supplementation focuses primarily on the oil extracted by pressing oil from the tiny seeds. One can also grind the seeds and use them as you would flax seed. The primary active ingredient found in evening primrose oil is the omega-6 polyunsaturated fatty acid (PUFA) gamma-linolenic acid, GLA (γ-linolenic acid). For more information on the dietary benefits of GLA and other PUFAs see the Omega Fatty Acid page.

Evening primrose oil is best known for its use in the treatment of systemic diseases marked by chronic inflammation, such as atopic dermatitis and rheumatoid arthritis. It is often touted for use in treating several women's health conditions, including breast pain (mastalgia), menopausal and premenstrual symptoms, cervical ripening, and labor induction or augmentation. Evening primrose oil has also been used for decreasing the risk of heart disease by lowering cholesterol and by decreasing the risk of blood clots (by decreased platelet aggregation). Evening primrose oil has also been used to treat certain skin conditions such as eczema. However, there is insufficient evidence to make a reliable assessment of its effectiveness for most clinical indications. Current evidence suggests that oral evening primrose oil does not provide clinically significant improvement in persons with atopic dermatitis, and that it is also likely ineffective for the treatment of cyclical mastalgia and premenstrual syndrome. However, most trials to date have significant methodologic flaws and must be considered as only preliminary. The use of evening primrose oil during pregnancy is not supported in the literature and should be avoided. Evening primrose oil is generally well tolerated, with reported minor adverse effects, including gastrointestinal upset and headaches.

Bayles B, and Usatine R 2009. Evening primrose oil. Am. Fam. Physician. 80(12):1405-1408.

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Fenugreek (Trigonella foenum-graecum): Fenugreek is a member of the Fabaceae family of plants. The leaves of the plant are used as an herbal and the seeds are used as a spice. The primary use for fenugreek as a dietary supplement is to increase the production of milk. Fenugreek has also been reported to reduce blood glucose making it potentially useful for diabetics, reduce cholesterol, and has been used to treat skin inflammations, asthma, and allergies. The only scientific studies that have assessed the medicinal efficacy of fenugreek involve its ability to lower blood glucose in diabetics.

In a recent study of drug-induced diabetes in rats fenugreek oil was shown to significantly improve blood glucose levels, glucose intolerance, and insulin sensitivity compared to the diabetic group. Administration of fenugreek oil to these diabetic rats lead to a reduction in pancreatic β-cell damage (the β-cells secrete insulin). The diabetic rats in this study exhibited low activities of superoxide dismutase (SOD), catalase, glutathione peroxidase, and reduced glutathione (GSH) content in kidney, which all were restored to near normal levels by treatment with fenugreek oil. Increased levels of lipid peroxidation, creatinine, albumin, and urea in diabetic rats were significantly reduced in diabetic rats treated with fenugreek oil. Diabetic rats treated with fenugreek oil exhibited an almost normal architecture of pancreas and kidney. This data suggests that the action of fenugreek oil in the amelioration of diabetes, hematological status, and renal toxicity may be attributed to its immunomodulatory activity and insulin stimulation action along with its antioxidant potential.

Another recent study demonstrates that the route of administration of fenugreek can have a significant impact on trial results. A study of fenugreek effects on serum glucose and lipid profiles was carried out in type 2 diabetes patients. One group was given 10 grams/day of powdered fenugreek in yogurt or tea made by soaking the same amount of powdered fenugreek in hot water. After 8 weeks of treatment, serum glucose, triglycerides, and LDL cholesterol levels were found to be significantly decreased only in the patients taking the fenugreek tea. It is believed that the treatment of the fenugreek powder in hot water allowed for the leaching out of the critically important oils from the plant resulting in a higher effective bioavailability.

Hamden K, Masmoudi H, Carreau S, and Elfeki A 2010. Immunomodulatory, beta-cell, and neuroprotective actions of fenugreek oil from alloxan-induced diabetes. Immunopharmacol. Immunotoxicol. Jan 25 Epub ahead of print.

Kassaian N, Azadbakht L, Forghani B, and Amini M 2009. Effect of fenugreek seeds on blood glucose and lipid profiles in type 2 diabetic patients. Int. J. Vitam. Nutr. Res. 79(1):34-39.

Lesiak K, Koprowska K, Zalesna I, Nejc D, Düchler M, and Czyz M 2010. Parthenolide, a sesquiterpene lactone from the medical herb feverfew, shows anticancer activity against human melanoma cells in vitro. Melanoma Res. 20(1):21-34.

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Feverfew (Tanacetum parthenium): Feverfew is a member of the sunflower family. Feverfew has been used for centuries to treat fevers (hence the derivation of its name), headaches, stomach aches, toothaches, insect bites, infertility, psoriasis, allergies, asthma, tinnitus (ringing or roaring sounds in the ears), dizziness, nausea, vomiting, and problems with menstruation and with labor during childbirth.

Recently feverfew has been touted for its use in treating migraine headaches and rheumatoid arthritis. The effect of feverfew on migraines is likely due to extracts from the plant having the ability to block the release of serotonin (5-hydroxytryptamine, 5-HT) as well as block the activation of the 5-HT2A and 5-HT2B receptors in the brain as demonstrated in rats. The effects of powdered feverfew in reducing 5-HT actions in rat brain was not due to the presence of parthenolide, which is one bioactive molecule extracted from feverfew, since purified parthenolide did not exhibit the same effects in these studies.

Most recent clinical studies of feverfew activity utilize the primary component from the plant which is parthenolide. Parthenolide is a sesquiterpene lactone that exhibits antitumor activity which is why it has received attention in the clinical arena. This antitumor action of parthenolide stems from its cytotoxicity to tumor cells primarily as a result of the induction of apoptosis. The anticancer property of parthenolide has been demonstrated in both in vitro cell culture and in vivo animal models. In studies on human cancer cells parthenolide was shown to sensitize cells to the killing action of tumor necrosis factor-alpha (TNF-α). This sensitization occurred as a consequence of parthenolide suppression of the activation of the nuclear transcription factor-kappaB (NF-κB) and the sustained activation of the transcription factor regulator c-Jun N-terminal kinase (JNK).

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Garlic (Allium sativum): Garlic is primarily used as an herbal supplement for the treatment of hypercholesterolaemia and prevention of atherosclerosis. Garlic provides cardiovascular protection by reducing serum cholesterol, reducing blood pressure, exerting anti-platelet activities (thus preventing abnormal clot formation), and inhibiting the formation of pro-inflammatory eicosanoids such as thromboxanes (see The Medical Biochemistry Page for more detail). The sulfur containing metabolite, allicin (and its derivatives) is thought to be a major compound in the cardiovascular benefits of garlic.

Evidence also suggests that aged garlic extracts may have benefits as anti-cancer agents. Different garlic preparations including fresh garlic extract, aged garlic, garlic oil and a number of organosulfur compounds derived from garlic have demonstrated chemopreventive action. The two major compounds in aged garlic, S-allylcysteine and S-allylmercapto-L-cysteine, have been shown to have the highest reactive oxygen species (ROS) and free radical scavenging activity. In addition, some organosulfur compounds derived from garlic, including S-allylcysteine, have been found to retard the growth of chemically induced and transplantable tumors in several animal models. The anti-cancer effects of garlic are thought to be due to its antioxidant properties which could be useful in preventing the suppression of immune responses associated with increased risk of malignancy. Garlic stimulates the proliferation of lymphocytes, macrophage phagocytosis, stimulates the release of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), and enhances natural killer cells. Therefore, the consumption of garlic may provide some kind of protection from cancer development.

Persons taking garlic supplements should be aware that several clinical trials have shown that compounds in the herbal supplement can affect the bioavailability of numerous prescription medications. Garlic interacts with chlorpropamide (Diabinase: sulfonylurea class of drug used to lower blood glucose in type 2 diabetes), fluindione (anticoagulant with mode of action like that of warfarin), ritonvir (Norvir: a protease inhibitor used as a component of highly active antiretroviral therapy, HAART), and warfarin (Coumadin, Jantoven, Marevan, Lawarin, Waran: anticoagulant). Thus, it is strongly advised that individuals consult their physician prior to consuming garlic supplements. One case study suggested that garlic might influence platelet function and blood coagulation, leading to a risk of bleeding. However, two clinical trials have reported that garlic (enteric-coated tablets or aged garlic extract) did not alter the pharmacokinetics or pharmacodynamics of warfarin and that garlic poses no serious increased bleeding risk for adequately monitored patients taking warfarin.

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Ginger (Zingiber officinale): Zingiber officinale is commonly known as red ginger. Ginger is the rhizome (the horizontal stem of a plant found underground) of the plant. The characteristic odor and flavor of ginger is the result of a mixture of volatile oils that includes zingerone, shogaols and gingerols. Gingerols have been shown to increase the motility of the gastrointestinal tract and have analgesic, sedative, antipyretic and antibacterial properties when assayed in laboratory animals.

Red ginger has been prescribed as an analgesic for arthritis pain in Indonesian traditional medicine. The surface color of the rhizome is purple because of the anthocyanidins (polyphenolic antioxidants) in its peel. Dried red ginger extract has been evaluated for its anti-inflammatory activity using acute and chronic inflammation models. The anti-inflammatory mechanism of red ginger extracts were tested by examining their effects on prostaglandin and nitric oxide (NO) production from mouse leukemic monocytes that had been stimulated by treatment with lipopolysaccharide. Ginger extracts (3 and 10 micrograms/milliliter, μg/mL) significantly suppressed PGE2 production, while it also suppressed NO production at 100μg/mL. By separating the bioactive compounds in red ginger extract it was found that 6-shogaol and gingerdiols suppressed NO production. Fractions presumed to be proanthocyanidins also suppressed NO production at 100μg/mL. These results demonstrated a potent suppressive effect of red ginger extract on acute and chronic inflammation, and inhibition of macrophage activation seems to be involved in this anti-inflammatory effect. The compounds 6-shogaol, gingerdiols, and proanthocyanidins were identified as constituents that inhibited NO production.

Shimoda H, Shan SJ, Tanaka J, Seki A, Seo JW, Kasajima N, Tamura S, Ke Y, and Murakami N 2010. Anti-inflammatory properties of red ginger (Zingiber officinale var. Rubra) extract and suppression of nitric oxide production by its constituents. J. Med. Food. 13(1):156-162.

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Ginkgo biloba: The ginkgo tree is one of the oldest types of trees in the world. Ginkgo seeds have been used in traditional Chinese medicine for thousands of years. Ginkgo leaf extract has been used to treat asthma, bronchitis, fatigue, and tinnitus (ringing or roaring sounds in the ears). More recent uses of ginkgo leaf extracts are for improving memory; to treat or help prevent Alzheimer's disease and other types of dementia. However, a National Center for Complimentary and Alternative Medicine (NCCAM)-funded study of the well-characterized ginkgo product, EGb-761, found it ineffective in lowering the overall incidence of dementia and Alzheimer's disease in the elderly. Additional analysis of the same data also found ginkgo to be ineffective in slowing cognitive decline. Ginkgo extracts have also been touted for the treatment of sexual dysfunction, vascular dysfunction, insulin resistance, and multiple sclerosis. Extracts from ginkgo biloba have been shown to contain eight flavonoid compounds, namely rutin, myricetin, quercitrin, quercetin, luteolin, kaempferol, apigenin, and isorhamnetin.

Analysis of gene expression profiles using microarrays is a potentially practical approach for understanding the mechanism of toxicities associated with herbal supplements such as ginkgo biloba. In a study involving laboratory mice, microarrays were used to analyze gene expression changes in the livers of male B6C3F1 mice administered ginkgo biloba leaf extract (GBE) by gavage (use of a tube into the stomach to administer food) for 2 years. Analysis of 31,802 genes revealed that there were 129, 289, and 2,011 genes significantly changed in the 200, 600, and 2,000 mg/kg treatment groups, respectively, when compared with control animals. Drug metabolizing genes were significantly altered in response to GBE treatments. Pathway and network analyses were applied to investigate the gene relationships, functional clustering, and mechanisms involved in GBE exposure. These analyses indicate alteration in the expression of genes coding for drug metabolizing enzymes, the NRF2-mediated oxidative stress response pathway, and the Myc gene-centered network named "cell cycle, cellular movement, and cancer" were found. These results indicate that ginkgo biloba-related drug metabolizing enzymes may cause herb-drug interactions and contribute to hepatotoxicity.

Persons taking ginkgo biloba supplements should be aware that several clinical trials have shown that compounds in the herbal supplement can affect the bioavailability of numerous prescription medications. Consumption of ginkgo extracts results in reduced plasma concentrations of omeprazole (Prilosec, Zegerid: proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease, PUD, and gastroesophageal reflux disorder, GERD), ritonvir (Norvir: a protease inhibitor used as a component of highly active antiretroviral therapy, HAART), and tolbutamide (Orinase: a first generation sulfonylurea class of drug used to lower blood glucose in type 2 diabetes). Thus, it is strongly advised that individuals consult their physician prior to consuming ginkgo biloba supplements.

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Ginseng (Panax ginseng): Ginseng refers to several species of plant of the Panax family. The genus name Panax is derived from the Greek word meaning "universal remedy" and demonstrates the fact that ginseng has been used as an herbal medicine for thousands of years. The Chinese added ginseng to everything from food to soaps and lotions. The principal bioactive molecules found in ginseng root extracts are saponins (see above in discussion of Astragalus for explanation of what is a saponin). The saponins in ginseng are referred to as ginsenosides. The potential health effects of ginsenosides that have been studied include anticarcinogenic, immunomodulatory, anti-inflammatory, antiallergic, antiatherosclerotic, antihypertensive, and antidiabetic effects as well as antistress activity and effects on the central nervous system. Ginsensoides can be metabolized in the stomach (acid hydrolysis) and in the gastrointestinal tract (bacterial hydrolysis) or transformed to other ginsenosides by drying and steaming of ginseng to more bioavailable and bioactive ginsenosides. To date more than 150 naturally occurring ginsenosides have been isolated from roots, leaves/stems, fruits, and/or flower heads of ginseng.

Ginseng has been touted as a remedy for numerous ailments but due to poorly controlled studies there is little convincing clinical data to support many of the claims made for ginseng. For example the use of ginseng has been promoted to aid in the treatment of ADHD, to aid in weight gain and immune function in patients undergoing chemotherapy, as a supplement that can lower blood cholesterol, cancer risk, and blood pressure, as well as useful in the treatment of erectile dysfunction. There is only suggestive evidence at best, for the effectiveness of red ginseng in the treatment of erectile dysfunction.

The evidence for the use of ginseng in the control of glucose levels in type 2 diabetes mellitus (T2DM) is more compelling:

Korean red ginseng has been studied in animal models for T2DM and peripheral insulin-responsive cell lines. In one study Korean red ginseng was administered orally, at a dose of 200 mg/kg per day, for 40 weeks to a particular strain of fatty rats. Chronic administration of the ginseng reduced weight gain and visceral fat mass in the early period of the study without altering food intake. These rats showed improved insulin sensitivity and significantly preserved glucose tolerance compared with untreated control animals. The Korean red ginseng promoted fatty acid oxidation in these animals by the activation of adenosine monophosphate-activated protein kinase (AMPK, see The Medical Biochemistry Page for more details on AMPK) and phosphorylation of acetyl-coenzyme A carboxylase (ACC, see The Medical Biochemistry Page for more details on ACC) in skeletal muscle and also cultured muscle cells. Increased expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), nuclear respiratory factor-1, cytochrome c, cytochrome c oxidase-4, and glucose transporter 4 (GLUT4) by Korean red ginseng treatment indicates that activated AMPK also enhanced mitochondrial biogenesis and glucose utilization in skeletal muscle. These findings suggest that Korean red ginseng is likely to have beneficial effects on the amelioration of insulin resistance and the prevention of T2DM through the activation of AMPK.

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a transcription factor that plays a key role in modulating glucose and lipid metabolism and in the pathogenesis of atherosclerosis (see The Medical Biochemistry Page for more details on PPARs). Some studies have reported that ginsenosides have anti-hyperglycemia and anti-obesity effects that involve the PPARγ-mediated pathway. One recent study investigated the effects of ginsenosides on the expression of PPARγ in mononuclear macrophages isolated from patients with T2DM as well as the response of these effects on glucose and lipid metabolism. Test subjects with T2DM who consumed 41mg/day ginsenosides had significantly higher levels of expression of  PPARγ compared with T2DM control patients. In addition, the total cholesterol and triglyceride levels were significantly decreased, and the blood glucose level also decreased (but without statistical significance) compared to the control group. These results demonstrate that ginsenosides improve PPARγ expression and lipid metabolism. Thus, it is indicative that ginsenosides may be applied as an adjuvant for treating type 2 diabetes.

American Ginseng (Panax quinquefolium) has been reported to reduce the rate of mortality in users who have breast cancer. To address this claim a study was undertaken to examine the effects of extracts from American ginseng on the inflammatory responses of human breast cancer cell lines in culture. When the cells were treated with the ginseng extract their rate of proliferation was reduced. At the molecular level this reduction was correlated to a reduced level of induction of and the pro-inflammatory transcription factor, NFκB and one of its target genes, COX-2 (an enzyme that synthesizes pro-inflammatory molecules). These results indicate that ginseng extracts have anti-inflammatory activity and that this activity suggests a possible mechanism for the anti-cancer effects of American ginseng.

Persons taking ginseng supplements should be aware that several clinical trials have shown that compounds in the herbal supplement can affect the bioavailability of numerous prescription medications. Ginseng has been shown to interact with phenelzine (Nardil: a non-selective and irreversible monoamine oxidase inhibitor (MAOI) class of antidepressant) and warfarin (Coumadin, Jantoven, Marevan, Lawarin, Waran: anticoagulant). Thus, it is strongly advised that individuals consult their physician prior to consuming ginseng supplements.

Peralta EA, Murphy LL, Minnis J, Louis S, and Dunnington GL 2009. American Ginseng inhibits induced COX-2 and NFKB activation in breast cancer cells. J. Surg. Res. 157(2):261-267.

Ni HX, Yu NJ, and Yang XH 2009. The study of ginsenoside on PPARgamma expression of mononuclear macrophage in type 2 diabetes. Mol. Biol. Reports E pub ahead of print.

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Gotu kola (Centella asiatica): Gotu kola is a member of the parsley family that thrives in and around water. It is a perennial plant native to India, Japan, China, Indonesia, South Africa, Sri Lanka, and the South Pacific. The leaves and stems of the gotu kola plant are used for medicinal purposes. Historically, gotu kola has also been used to treat syphilis, hepatitis, stomach ulcers, mental fatigue, epilepsy, diarrhea, fever, and asthma.

Today, gotu kola is most often used to treat psoriasis and help heal minor wounds and to treat chronic venous insufficiency (a condition where blood pools in the legs). Clinical studies done in accordance with standardized scientific criteria have shown gotu kola to have a positive effect in the treatment of venous insufficiency and abdominal stretch marks caused by pregnancy (clinically referred to as striae gravidarum). The use of gotu kola for the treatment of hemorrhoids and varicose veins (conditions related to venous insufficiency) is supported by current clinical studies but is not yet proven to be truly beneficial for these conditions. In addition, good clinical data shows that gotu kola is effective in the treatment of wound healing disturbances. However, clinical studies, in humans, aimed at investigating the sedative, analgesic, antidepressive, antimicrobial, and antiviral effects are still lacking even though there is available animal and cell culture data for some of these uses.

The primary bioactive compounds found in gotu kola are pentacyclic triterpenoid saponins, collectively known as centelloids. These terpenoids include asiaticoside, centelloside, madecassoside, brahmoside, brahminoside, thankuniside, sceffoleoside, centellose, asiatic-, brahmic-, centellic- and madecassic acids. The triterpenoids from gotu kola can be regarded as phytoanticipins due to their antimicrobial activities and protective role against attempted pathogen infections in the plant. Gotu kola extracts also contain numerous polyphenolic antioxidants with the highest amounts being quercetin, myricetin, and kaempferol.

Asiaticoside is one of the major triterpenoid saponin components isolated from gotu kola and it has been shown to exhibit antioxidant and anti-inflammatory activities. The anti-inflammatory activity of gotu kola asiaticoside was recently assessed in a mouse model of septic lung injury. In this study, mice were pretreated with asiaticoside (45mg/kg) alone or with asiaticoside along with the peroxisome proliferator-activated receptor-gamma (PPARγ) inhibitor GW9662 and examined for survival, lung injury, inflammatory mediators, signaling molecules, and PPARγ levels. Results of the study showed that asiaticoside significantly decreased treatment-induced mortality, lung pathological damage, infiltration of mononuclear, polymorphonuclear (PMN) leucocytes and total proteins. In addition, asiaticoside inhibited treatment-induced activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NFκB), the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein in lung tissues, and the production of serum tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Of significance, the expression of PPARγ protein in lung tissue was up-regulated by asiaticoside and reversed by co-treatment with GW9662 (the PPARγ inhibitor). These results suggest that asiaticoside may be useful in the protection from inflammatory injury via its ability to up-regulate of PPARγ expression which in turn inhibits the MAPKs and NFκB signal transduction pathways.

Zhang LN, Zheng JJ, Zhang L, Gong X, Huang H, Wang CD, Wang B, Wu MJ, Li XH, Sun WJ, Liu YJ, and Wan JY 2010. Protective effects of asiaticoside on septic lung injury in mice. Exp. Toxicol. Pathol. May 12 Epub ahead of print.

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Grape seed (Vitis vinifera): Grapes themselves have been touted for their medicinal and nutritional benefits for thousands of years. An ointment made from the sap of grapevines was used by European folk healers to treat skin and eye diseases. Grape leaves have been used to stop bleeding and to reduce inflammation and pain, such as the kind brought on by hemorrhoids. Unripe grapes were used to treat sore throats and raisins were used for constipation and thirst. Ripe sweet grapes were used to treat a range of health problems including cancer, cholera, smallpox, nausea, eye infections, and skin, kidney, and liver diseases. Grape seed extract is used for conditions related to the heart and blood vessels, such as atherosclerosis (hardening of the arteries), high blood pressure, high cholesterol, and poor circulation. Additional uses for grape seed extract include complications related to diabetes, such as nerve and eye damage; vision problems, such as macular degeneration (which can cause blindness), and swelling after an injury or surgery. Grape seed extract has also been used for cancer prevention and wound healing.

Grape seed extract has antioxidant and free radical scavenging activity. Grape seed extracts contain a complex mixture of bioactive compounds including vitamin E, linoleic acid, gallic acid, catechin, epicatechin and several oligomeric proanthocyanidins (OPCs) of catechin and/or epicatechin, some of which are esterified to gallic acid. The anti-cancer efficacy of grape seed extract against prostate cancer via its anti-proliferative, pro-apoptotic and anti-angiogenic activities in both cell culture and animal models have recently been shown to be the result of the activity of gallic acid. Several proanthocyanidins, and especially the gallate esters of dimers and trimers may also be efficacious against prostate cancer. The proanthocyanidins present in grape seeds have been shown to have some biological effects, including prevention of photocarcinogenesis.

Resveratrol is an potent non-flavonoid polyphenolic antioxidant chemical found in grape seeds and skin. Numerous biologically significant activities of resveratrol have been demonstrated in cell culture, animal models and in humans. The details of resveratrol action are covered in the Resveratrol page.

In human volunteers the consumption of red and/or purple grape juice has been shown to have cardioprotective effects. Consumption of purple grape juice (around 8 ml/kg/day) for 14 days in adults with angiographically documented coronary artery disease led to improved flow-mediated vasodilation (FMD) and reduced LDL oxidation susceptibility. In a related study, consumption of 4–8 ml/kg/day of purple grape juice for 4 weeks in patients with coronary heart disease improved FMD. Consumption of 7 ml/kg/day of purple grape juice for 14 days in 20 healthy subjects showed inhibited platelet aggregation, reduced superoxide release, and increased platelet-derived nitric oxide (NO) production. In a related study, in vitro incubation of human platelets with purple grape juice showed similar results. Administration of purple grape juice (500 ml/ day) from 14 days to 16 to hypercholesterolemic individuals without other risk factors improved their FMD. Consumption of concentrated red grape juice (50 ml, twice a day, for two weeks) resulted in increased antioxidant capacity of plasma, reduced the concentration of oxidized LDL and increased the plasma concentration of α-tocopherol (vitamin E, another potent antioxidant). In healthy volunteers who consumed 300mg of a proanthocyanidin-rich grape seed extract, oxidative stress was minimized by decreasing the level of oxidants and increasing the antioxidant levels in plasma. All of these results indicated that grape juice consumption can increase the resistance to oxidative modification of LDL which is important for reducing the likelihood of developing athersclerosis. Another study which had well defined measurements of the polyphenolic content of red grape extract showed that consumption of 600mg of the extract improved endothelial cell function in patients with coronary heart disease. These extracts contained 4.32mg epicatechin, 2.72mg catechin, 2.07mg gallic acid, 0.9mg trans-resveratrol, 0.47mg rutin, 0.42mg epsilonviniferin, 0.28mg, p-coumaric acid, 0.14mg ferulic acid and 0.04mg quercetin per gram.

In laboratory mice, dietary supplementation with grape seed proanthocyanidins reduces the effects of UV-irradiation such as oxidative stress, activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NFκB) signaling pathways. In addition there is an associated immunosuppression resulting from alterations in immunoregulatory cytokines. These studies indicate that there is a protective potential of grape seed proanthocyanidins against experimental photocarcinogenesis in mice, and that the mechanisms of action of these extracts is suggestive that dietary supplementation with grape seed extracts could be useful in the attenuation of the adverse UV-induced health effects in human skin.

Katiyar SK 2008. Grape seed proanthocyanidines and skin cancer prevention: inhibition of oxidative stress and protection of immune system. Mol. Nutr. Food Res. 52 Suppl 1:S71-S76.

Nassiri-Asl M, and Hosseinzadeh H 2009. Review of the pharmacological effects of Vitis vinifera (Grape) and its bioactive compounds. Phytother. Res. 23(9):1197-1204.

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Green tea (Camellia sinensis): There are three main varieties of tea: green, black, and oolong all of which are prepared from the leaves of Camellia sinensis. The difference between the teas relates to the way in which they are processed. Green tea is made from unfermented leaves and is believed to contain the highest levels of bioactive compounds. The primary bioactive molecules in green tea are the polyphenolic compounds catechin, gallogatechin, epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate, and epigallocatechin.

Green tea is purported to enhance humoral and cell-mediated immunity, decreasing the risk of certain cancers, as well as having certain advantages in treating inflammatory disorders. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest. This action of EGCG occurs via it altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing nuclear factor kappa-B (NFκB) activation. In addition EGCG regulates and promotes interleukin-23 (IL-23) dependent DNA repair and stimulates cytotoxic T cells activities in a tumor microenvironment. EGCG also blocks carcinogenesis by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation and metastasis. These anti-cancer activities of green tea support its potential as a chemopreventive agent against colon, stomach, skin, lung, prostate, ovarian, and breast cancer. It is important to note that green tea (as well as black tea) extracts have also been shown to stimulate genes that cause cells to be less sensitive to chemotherapy drugs. Thus, people should not consume green tea or green tea extracts (or black tea for that matter) while receiving chemotherapy.

Green tea extracts have also been shown to result in a reduction in serum cholesterol in animals and in man. Part of the effect on serum cholesterol is the result of suppression of hepatic cholesterol synthesis. This suppression is the result of components in the extract inhibiting the rate-limiting enzyme of cholesterol biosynthesis HMG-CoA reductase (HMGR; see The Medical Biochemistry Page for details) as well as activating the potent metabolic regulatory enzyme AMP-activated kinase (AMPK; see the The Medical Biochemistry Page for details). Additional studies have suggested that green tea polyphenols inhibit the absorption of cholesterol from the gut as well as lead to enhanced excretion. The reduction in serum cholesterol in persons consuming green tea may be associated with a reduction in the risk of atherosclerosis and coronary heart disease. Although tea manufacturers wanted to label their product as being associated with a reduced risk of heart disease, the US FDA rejected those claims since there was insufficient clinical data to warrant the claims.

Recent data demonstrate that EGCG can ameliorate the negative effects of free fatty acids (FFAs) on insulin function resulting in increased insulin sensitivity. Excess intracellular and intravascular FFAs (as is the situation in diabetic and obese individuals) result in the accumulation of fatty acid metabolic byproducts, such as ceramides, fatty acyl-CoAs, and diacylglycdrol. These excess metabolites activate a series of kinases that phosphorylate proteins involved in insulin functions within cells. The result of the phosphorylations is inhibition of insulin function resulting in insulin resistance. For more details on fatty acid metabolism and insulin functions visit the Lipid Metabolism page and the Insulin Function page at The Medical Biochemistry Page. EGCG has been shown to prevent FFAs-induced peripheral insulin resistance, increases the activity of AMPK (which is a master controller of metabolism) by inhibiting a negative phosphorylation reaction, and increases the level and activity of antioxidant enzymes.

Li Y, Zhao S, Zhang W, Zhao P, He B, Wu N, and Han P 2011 Epigallocatechin-3-O-gallate (EGCG) attenuates FFAs-induced peripheral insulin resistance through AMPK pathway and insulin signaling pathway in vivo. Diabetes Res. Clin. Pract. Epub April 21, 2011.

Butt MS, and Sultan MT 2009. Green tea: nature's defense against malignancies. Crit. Rev. Food Sci. Nutr. 49(5):463-473.

Tachibana H 2009. Molecular basis for cancer chemoprevention by green tea polyphenol EGCG. Forum Nutr. 61:156-169.

Yung LM, Leung FP, Wong WT, Tian XY, Yung LH, Chen ZY, Yao XQ, and Huang Y 2008. Tea polyphenols benefit vascular function. Inflammopharmacology. 16(5):230-234.

Yang CS, Wang X, Lu G, and Picinich SC 2009. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat. Rev. Cancer 9(6):429-439.

Singh DK, Banerjee S, and Porter TD 2009. Green and black tea extracts inhibit HMG-CoA reductase and activate AMP kinase to decrease cholesterol synthesis in hepatoma cells. J. Nutr. Biochem. (10):816-822.

Srivastava JK, and Gupta S 2007. Antiproliferative and apoptotic effects of chamomile extract in various human cancer cells. J. Agric. Food Chem. 55(23):9470-9478.

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Guggal (Commiphora wightii and Commiphora mukul): In the Ayurvedic tradition of medicine, any resin that is collected by tapping the trunk of a tree is called guggul (or guggal). The cholesterol lowering action of the guggul from the Mukul myrrh tree of India is that a lipid component of this extract called guggulsterone (also called guggul lipid) is an antagonist of a class of receptors called the farnesoid X receptors, FXRs. The FXRs belong to the superfamily of nuclear receptors (see The Medical Biochemistry Page) that includes the steroid/thyroid hormone receptor family (see The Medical Biochemistry Page) as well as the liver X receptors (LXRs), retinoid X receptors (RXRs), and the peroxisome proliferator-activated receptors (PPARs).

Like all receptors of this superfamily, ligand binds the receptor in the cytoplasm and then the complex migrates to the nucleus and forms a heterodimer with other members of the family. FXR forms a heterodimer with members of the RXR family. Following heterodimer formation the complex binds to specific sequences in target genes called hormone response elements (HREs) resulting in regulated expression. One major target of FXR is the small heterodimer partner (SHP) gene. Activation of SHP expression by FXR results in inhibition of transcription of SHP target genes. Of significance to the effects of guggulsterone on cholesterol levels, SHP represses the expression of the cholesterol 7-hydroxylase gene (CYP7A1). CYP7A1 is the rate-limiting enzyme in the synthesis of bile acids from cholesterol (for more on cholesterol and bile synthesis and regulation visit The Medical biochemistry Page). In addition to its effects on FXR function, guggulsterone has been shown to activate the pregnane X receptor (PXR) which is another member of the nuclear receptor superfamily. PXR is a recognized receptor for lithocholic acid and other bile acid precursors. PXR activation leads to repression of bile acid synthesis due to its physical association with hepatocyte nuclear factor 4α (HNF-4α) causing this transcription factor to no longer be able to associate with the transcriptional co-activator PGC-1α (PPARγ co-activator 1α) which ultimately leads to loss of transcription factor activation of CYP7A1.

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Gymnema sylvestre: Gymnema sylvestre is a member of the plant family Asclepiadaceae. It grows in the tropical forests of central and southern India. Due to its ability to induce a reduction in blood glucose levels it is used in Ayurvedic medicine to treat diabetes. In India the plant is referred to as gurmar which means sugar destroyer in Hindi. One of the active compound from this plant is actually a group of acids termed gymnemic acids. Gymnemic acids have antidiabetic, antisweetener and anti-inflammatory activities. The plant is also used for controlling obesity in the form of Gymnema tea. This herbal supplement is also used in the treatment of asthma, eye complaints, inflammations, and snakebite. In addition, it possesses antimicrobial, antihypercholesterolemic, hepatoprotective and sweet suppressing activities.

Extracts from the leaves Gymnema sylvestre contain triterpene saponins belonging to oleanane and dammarene classes. Oleanane saponins are gymnemic acids and gymnemasaponins, while dammarene saponins are gymnemasides. Besides these compounds, the plant contains flavones, anthraquinones, hentri-acontane, pentatriacontane, α and β-chlorophylls, phytin, resins, d-quercitol, tartaric acid, formic acid, butyric acid, lupeol, β-amyrin related glycosides and stigmasterol. The plant extracts also test positive for alkaloids. Leaves of this species yield acidic glycosides and anthroquinones and their derivatives.

The anti-obesity related actions of gymnemic acid formulations is attributed to the ability of gymnemic acids to delay the absorption of glucose into the blood. Gymnemic acid molecules resemble glucose molecules, thus these acids fill the receptor locations on the taste buds thereby preventing its activation by sugar molecules present in the food, thereby curbing the sugar craving. Similarly, gymnemic acid molecules fill the receptor location in the absorptive external layers of the intestine thereby preventing the absorption of sugar molecules by the intestine, which results in a reduction in blood sugar levels.

Al-Romaiyan A, Liu B, Asare-Anane H, Maity CR, Chatterjee SK, Koley N, Biswas T, Chatterji AK, Huang GC, Amiel SA, Persaud SJ, and Jones PM 2010. A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro. Phytother Res. 24(9):1370-1376.

Ahmed AB, Rao AS, and Rao MV. 2010. In vitro callus and in vivo leaf extract of Gymnema sylvestre stimulate β-cells regeneration and anti-diabetic activity in Wistar rats. Phytomedicine. 17(13):1033-1039.

Yadav M, Lavania A, Tomar R, Prasad GB, Jain S, and Yadav H 2010. Complementary and comparative study on hypoglycemic and antihyperglycemic activity of various extracts of Eugenia jambolana seed, Momordica charantia fruits, Gymnema sylvestre, and Trigonella foenum graecum seeds in rats. Appl. Biochem. Biotechnol. 160(8):2388-2400.

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Kava kava (Piper methysticum): Kava is a tall shrub that grows in the islands of the Pacific Ocean. A beverage is prepared from the plant by grinding the roots into a pulp and adding water. This concoction has been used as a ceremonial drink by Pacific islanders for hundreds of years.

The primary bioactive compounds found in kava root are called kavalactones (kavapyrones). These compounds include kawain, dihydrokawain, and methysticum. The biological activities of these compounds have been extensively studied in laboratory and animal studies. They have been shown to reduce convulsions, promote sleep, and relax muscles in animals. They also have pain-relieving properties, which may explain why chewing kava root tends to cause a temporary numbness and tingling sensation on the tongue.

Kava is best known for its relaxing qualities. Kava is said to elevate mood, well-being, and contentment, and produce a feeling of relaxation. Several studies have found that kava may be useful in the treatment of anxiety, insomnia, and related nervous disorders. However, there is serious concern that kava may cause liver damage. More than 30 cases of liver damage have been reported in Europe. It's not clear whether the kava itself was the cause of the liver damage or whether it was taking kava in combination with other drugs or herbs. Many mechanisms have been postulated to explain the unexpected toxicity, one being pharmacokinetic interactions between kavalactones and co-administered drugs that activate the drug metabolizing system (cytochrome P450, CYP) of the liver. Alcohol is often co-injested in reported cases kava hepatotoxicity cases. It's also not clear whether kava is dangerous at previously recommended doses, or only at higher doses. Some countries have taken kava off the market. It remains available in the United States, but the Food and Drug Administration issued a consumer advisory in 2002 expressing concern about liver damage in individuals who have ingested kava products.

Persons taking kava supplements should be aware that several clinical trials have shown that compounds in the herbal supplement can affect the bioavailability of numerous prescription medications. Kava increases the clearance of chlorzoxazone (Paraflex, Parafon Forte, Relaxazone, Remular-S: treatment of muscle spasms) and may interact with alprazolam (Xanax, Xanor, Alprax, Niravam: treatment of anxiety), levodopa (Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa: converted to dopamine in the body, used for treament of Parkinson disease), and paroxetine (Seroxat, Paxil: selective serotonin reuptake inhibitor (SSRI) antidepressant). Thus, it is strongly advised that individuals consult their physician prior to consuming kava supplements.

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Licorice (Glycyrrhiza glabra, Glycyrrhiza uralensis): The medicinally used part of licorice is the root and dried rhizome of the plant. Licorice is widely used in the Indian system of medicine. Licorice root has been used as a dietary supplement for stomach ulcers, bronchitis, and sore throat, as well as infections caused by viruses, such as hepatitis. Most licorice today is produced in Greece, Turkey, and Asia. Licorice extracts are purported to be active as anti-allergic, anti-inflammatory, spasmolytic, mild laxative, antistress, antidepressive, antiulcer, liver protective, estrogenic, emmenagogue (herbs which stimulate blood flow in the pelvic area and uterus), and antidiabetic substances. Clinical trials have found that glycyrrhizin might reduce complications from hepatitis C in some patients. However, there is not enough evidence to confirm that glycyrrhizin has this effect. There are insufficient clinical data to establish whether licorice is effective for stomach ulcers.

The major bioactive constituent of licorice is glycyrrhizin (also called glycyrrhizic acid) which consists of two molecules of glucuronic acid (a type of sugar) and one molecule of glycyrrhetic acid. However, chronic licorice consumption can lead to serious side effects due to the presence of considerable quantities of glycyrrhizin, which causes severe hypokalaemia and hypertension. Licorice root supplements are available as capsules, tablets, or liquid extracts. Because of the toxicity of glycyrrhizin some licorice supplements are prepared with the glycyrrhizin removed. These products are referred to as deglycyrrhizinated licorice (DGL).

Although licorice extracts are known to exhibit anti-cancer activities, the potential side-effects of chronic licorice consumption, due to the presence of glycyrrhizin, make this dietary supplement unacceptable as an adjunct to therapy. Studies using a hexane-ethanol extract of licorice, which lacks glycyrrhizin, demonstrated a reduction in the metastatic characteristics of human prostate cancer cells in culture. The active compound in this hexane-ethanol extraction of licorice was shown to be licoricidin. The treatment of these cancer cells with licoricidin induced a reduction in cell migration and the secretion of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), urokinase-type plasminogen activator and vascular endothelial growth factor (VEGF), as well as in the expression of adhesion molecules. These results indicate that licoricidin is a potent anti-metastatic agent, which can markedly inhibit the metastatic and invasive capacity of malignant prostate cancer cells.

The potential for licorice extracts to be used as adjuncts in the treatment of type 2 diabetes was demonstrated when it was shown that compounds in the extracts can activate peroxisome proliferator-activated receptor-gamma (PPARγ). PPARγ is the target of the thiazolidinedione (TZD) class of type 2 diabetes drugs (for more information of the action of the TZDs see The Medical Biochemistry Page). Characterization of the alcohol extraction products from licorice found that at least 39 different phenolic compounds can identified. Of these, 12 were shown to bind to PPARγ. Oral administration of glycyrrhizic acid to high-fat diet-induced obesity rats resulted in a significant reduction in blood glucose levels and improved insulin sensitivity. In addition, the level of lipoprotein lipase, LPL (the blood vessel enzyme that removes fatty acids from circulating lipoproteins such as LDLs) was increased in numerous tissues such as skeletal muscle and adipose tissue but reduced in the liver. The significance of the increase in LPL activity in the various tissue was evidenced by a reduction in circulating free fatty acids, triacylglycerols, and LDL cholesterol. An additionally significant observation in this study was that the levels of HDL cholesterol (so-called "good cholesterol") increased suggesting there may be antiatherosclerotic properties of glycyrrhizic acid.

In addition to glycyrrhizin, the roots of Glycyrrhiza uralensis, Mongolian glycyrrhiza, and Glycyrrhiza glabra, as well as other related members of the Glycyrrhiza family, contain isoliquiritigenin, a bioactive compound shown to exert anti-inflammatory, anti-microbial, anti-oxidative, and anti-cancer activities, as well as hepatoprotective, and cardioprotective effects and immune system modulating effects. Indeed, isoliquiritigenin is considered to be the main bioactive component of Glycyrrhiza roots and does not possess the potential toxic side effects exerted by glycyrrhizin. Most recent clinical studies on the effects of isoliquiritigenin have focused on its anti-cancer effects where it has been shown to be potent at inhibiting the growth of various forms of cancer cells. In addition isoliquiritigenin has been shown to be a potent anti-oxidant which allows it to prevent cancers, such as colon cancers, induced by exposure to oxidizing chemicals. In addition to isoliquiritigenin itself, the roots of the Glycyrrhiza family contain numerous derivatives that also exert potent biological effects.

Peng, F, Du, Q, Peng, Q, Wang, N, Tang, H, Xie, X, Shen, J, and Chen, J 2015. A Review: The Pharmacology of Isoliquiritigenin. Phytotherapy Res. 29:969-977

Eu CH, Lim WY, Ton SH, and bin Abdul Kadir K 2010. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats. Lipids Health Dis. 9:81

Park SY, Lim SS, Kim JK, Kang IJ, Kim JS, Lee C, Kim J, and Park JH 2010. Hexane-ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells. Br. J. Nutr. May Epub ahead of print.

Kuroda M, Mimaki Y, Honda S, Tanaka H, Yokota S, and Mae T 2010. Phenolics from Glycyrrhiza glabra roots and their PPAR-gamma ligand-binding activity. Bioorg. Med. Chem. 18(2):962-970.

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Milk thistle (Silybum marianum): Milk thistle belongs to the flowering plants of the daisy family (Asteraceae) and is native to the Mediterranean area but is now grown around the world. Milk thistle gets its name from the milky white fluid that comes from the leaves when they are crushed. Milk thistle has been used for thousands of years as an herbal remedy for a variety of ailments, particularly liver and gall bladder problems.

One of the primary bioactive components found in milk thistle is called silymarin. Silymarin is actually composed of four flavonolignane isomers: silibinin, isosilibinin, silidianin and silichristin. Silibinin, which is also known as silybinin or silybin, is the major component (60%–70%) of silymarin and exists is two chemically related forms (diastereoisomers) identified as silibinin A (silybin A) and silibinin B (silybin B). Sylamarin is reported to protect the liver from toxins, including certain drugs such as acetaminophen (Tylenol), which can cause liver damage in high doses. Silymarin has been shown to inhibit hepatitis C virus (HCV) infection and also displays antioxidant, anti-inflammatory, and immunomodulatory actions that contribute to its hepatoprotective effects. In addition to the hepatoprotective activity of silymarin, the complex may help the liver repair itself by growing new cells.

Silymarin and its major constituent, silibinin, has recently been shown to exert significant anti-neoplastic effects in a variety of in vitro and in vivo cancer models, including skin, breast, lung, colon, bladder, prostate and kidney carcinomas. Silibinin has clearly demonstrated inhibition of multiple cancer cell signaling pathways, including growth inhibition, inhibition of angiogenesis, chemosensitization, and inhibition of invasion and metastasis. The molecular mechanisms of silibinin-mediated antiproliferative effects are mainly via receptor tyrosine kinases, androgen receptor, signal transducers and activators of transcription (STATs), NF-kappaB (NFκB), cell cycle regulatory and apoptotic signaling pathways in various cancer cells. Targeting inhibition of proliferative pathways through silibinin treatment may provide a new approach for improving chemopreventive and chemotherapeutic effects.

Silymarin has a good safety profile, but little is known regarding its potential for drug interaction. Silymarin has limited effect on the pharmacokinetics of several drugs in vivo despite silymarin decreasing the activity of several liver detoxifying enzymes including the cytochrome P450 class (CYPs), UDP-glucuronosyltransferase (UGT), and reducing P-glycoprotein transport.

Cheung CW, Gibbons N, Johnson DW, and Nicol DL 2010. Silibinin--a promising new treatment for cancer. Anticancer Agents Med. Chem. 10(3):186-195.

Rambaldi A, Jacobs BP, and Gluud C 2007. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst. Rev. Oct 17;(4):CD003620.

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Morus alba: Morus alba is a member of the mulberry family (specifically white mulberry) of short-lived fast-growing trees/shrubs native to China and now cultivated around the world. The major purpose in the cultivation of mulberry is for the feeding of silkworms. The fruits of mulberry trees are also eaten and sometimes used for the making of wine. In traditional Chinese herbal medicine mulberry fruit, leaves, and bark are used in the treatment of various conditions. The fruits are used in the treatment of diabetes and constipation as well as to "tonify" the blood. The bark and leaves are used to treat fever, headache, coughs, wheezing, sore eyes, and to promote urination.

Extracts prepared from the fruits and leaves of mulberry are rich in antioxidants such as resveratrol, oxyresveratrol, anthocyanins, and flavonoids. Some of the characterized polyphenol flavonoids from mulberry include quercetin and kaempferol. Tea prepared from the leaves of mulberry trees is purported to be of benefit in treating the hyperglycemia (high blood sugar) associated with type 2 diabetes. The sugar lowering benefits of mulberry is most likely due, in part, to the presence of quercetin as this antioxidant polyphenol has been shown is several animal and human studies to reduce blood glucose levels. However, it should be noted that numerous compounds have been isolated from plant species that exhibit inhibitory activity towards the intestinal enzyme α-glucosidase which is responsible for digestion of complex sugars and results in release of glucose from many of these complex sugars. Indeed, there are numerous drugs that are used to treat the hyperglycemia associated with type 2 diabetes that are α-glucosidase inhibitors. Plant derived compounds that exhibit α-glucosidase inhibitory action include various phytosterols, alkaloids, polyphenols, flavonoids, anthraquinones, flavanone glucosides, flavonols, anthocyanins as well as various acids including chlorogenic acid, betulinic acid, syringic acid, vanillic acid, oleanolic acid, ellagic acid, and gallic acid. In addition to quercetin, mulberry extracts contain 1-deoxynojirimycin which has been shown to have potent α-glucosidase inhibiting activity and therefore, may also be involved in the glucose lowering activity associated with consumption of Morus alba extracts.

In addition to the blood sugar lowering effects of mulberry leaf extracts, these extracts have been shown to inhibit oxidative stress in adipose (fat) tissue in diabetic mice. This effect of mulberry is exerted via a reduction in the synthesis and release of potent pro-inflammatory factors from adipose tissue called adipocytokines while at the same time increasing the release of the adipose tissue hormone adiponectin which acts as a powerful anti-inflammatory and anti-oxidative stress hormone. Along with alterations in adipose tissue hormone secretion, Morus alba extracts increase the expression of anti-oxidant enzymes in the blood and liver including superoxide dismutase (SOD) and glutathione peroxidase, thereby enhancing a protective effect against oxidative damage. The effects of Morus alba extracts on adipose tissue are similar to and act additively with the class of diabetes drugs called thiazolidinediones (TZDs) such as Actos® originally produced by Eli Lilly and Co. and now sold by Takeda. Addition of Morus alba fruit to the diet of high-fat diet fed animals demonstrated significant positive effects on the lipid profile of the blood of these animal suggesting that human consumption could provide benefit in cases of hyperlipidemias such as hypercholesterolemia. Animals fed mulberry fruit along with a high-fat diet showed reductions in serum triglycerides, cholesterol and low density lipoproteins (LDLs: "bad" cholesterol) while at the same time elevating serum high density lipoproteins (HDLs: "good" cholesterol) in comparison to animals who did not consume mulberry fruit.

Another critical benefit of extracts from mulberry leaves and bark is the potential to act as anti-cancer agents. Polyphenolic extracts of Morus alba have been shown to induce apoptosis (programmed cell death) in several types of cancer cells in culture including liver cancers. Again the likely compound exerting these anti-cancer effects is quercetin since it has demonstrated cancer killing activities in numerous assays.

Naowaratwattana W, De-Eknamkul W, and De Mejia EG 2010. Phenolic-containing organic extracts of mulberry (Morus alba L.) leaves inhibit HepG2 hepatoma cells through G2/M phase arrest, induction of apoptosis, and inhibition of topoisomerase IIα activity. J. Med. Food. 13(5):1045-1056.

Benalla W, Bellahcen S, and Bnouham M 2010. Antidiabetic medicinal plants as a source of alpha glucosidase inhibitors. Curr. Diabetes Rev. 6(4):247-254.

Yang X, Yang L, and Zheng H 2010. Hypolipidemic and antioxidant effects of mulberry (Morus alba L.) fruit in hyperlipidaemia rats. Food Chem. Toxicol. 48(8-9):2374-2379.

Liu LK, Lee HJ, Shih YW, Chyau CC, and Wang CJ 2008. Mulberry anthocyanin extracts inhibit LDL oxidation and macrophage-derived foam cell formation induced by oxidative LDL. J Food Sci. 73(6):H113-H121.

Sugimoto M, Arai H, Tamura Y, Murayama T, Khaengkhan P, Nishio T, Ono K, Ariyasu H, Akamizu T, Ueda Y, Kita T, Harada S, Kamei K, and Yokode M 2009. Mulberry leaf ameliorates the expression profile of adipocytokines by inhibiting oxidative stress in white adipose tissue in db/db mice. Atherosclerosis 204(2):388-394.

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Phyllanthus niruri: This herb is more commonly known by the common names stone-breaker, chanca piedra and quebra pedra. The herb also has many other common names in assorted languages, including dukong anak, dukong-dukong anak, amin buah, rami buah, turi hutan, and bhuiaonla. One of the principal uses of Phyllanthus niruri is in the treatment of kidney stones (urinary calculi) and in individuals prone to stones, hence the common name of stone-breaker.

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Reishi (Ganoderma lucidum): Reishi is an edible mushroom. Powdered reishi has been widely used for the general promotion of health and longevity in Asian countries and as a cancer chemotherapy agent in ancient China. The basidiocarp, mycelia and spores of Ganoderma lucidum contain approximately 400 different bioactive compounds, which mainly include triterpenoids, polysaccharides, nucleotides, sterols, steroids, fatty acids, and proteins/peptides. These various compounds have been reported to have a number of pharmacological effects including immunomodulation, anti-atherosclerotic, anti-inflammatory, analgesic, chemo-preventive, antitumor, chemo and radio protective, sleep promoting, antibacterial, antiviral (including anti-HIV), hypolipidemic, anti-fibrotic, hepatoprotective, anti-diabetic, anti-androgenic, anti-angiogenic, anti-herpetic, antioxidative and radical-scavenging, anti-aging, hypoglycemic, estrogenic activity and anti-ulcer properties.

Reishi extracts have been shown to inhibit the constitutively active transcription factors nuclear factor kappa B (NF-kappaB) and AP-1. This inhibition resulted in suppression of cell adhesion and cell migration of highly invasive breast and prostate cancer cells, suggesting its potency to reduce tumor invasiveness. Thus, reishi demonstrates anticancer activity in experiments with cancer cells and has possible therapeutic potential as a dietary supplement for an alternative therapy for breast and prostate cancer. Ganoderma lucidum has now become recognized as an alternative adjuvant in the treatment of leukemia, carcinoma, hepatitis and diabetes.

Lin ZB, and Zhang HN 2004. Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms. Acta Pharmacol. Sin. 25(11):1387-1395.

Sanodiya BS, Thakur GS, Baghel RK, Prasad GB, and Bisen PS 2009. Ganoderma lucidum: a potent pharmacological macrofungus. Curr. Pharm. Biotechnol. 10(8):717-742.

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Rauwolfia serpentina: Rauwolfia serpentina (also spelled Rauvolfina), commonly called "snakeroot" or "serpentwood", is a member of the plant family Apocynaeae (dogbane) that consists of trees and shrubs that are found in tropical rain forests. The plant name is derived from German physician and botanist Leonhard Rauwolf. Rauwolfia has been used in the tradition of Indian Ayruvedic medicine as a treatment for hypertension, nervousness and insomnia. It is also known in India as the "insanity herb," and is recommended for treating various mental disorders. The roots of the plant contain the alkaloid reserpine which has potent sedative effects. Reserpine and related compounds are components of several prescription tranquilizers.

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Saw Palmetto (Serenoa repens): Herbal supplements of saw palmetto are derived from the fruit of the plant.

Saw palmetto is popular in Europe for symptoms associated with benign prostatic hypertrophy or hyperplasia, BPH (enlargement of the prostate). Saw palmetto is the most popular herbal treatment for BPH. A large study of 225 men with moderate-to-severe BPH found no improvement with 320 mg saw palmetto daily for one year versus placebo. There is not enough scientific evidence to support the use of saw palmetto for reducing the size of an enlarged prostate or for any other conditions. Saw palmetto does not appear to affect readings of prostate-specific antigen (PSA) levels. The PSA test is used to screen for prostate cancer and to monitor patients who have had prostate cancer.

As part of the above study, detailed data were collected on serious and non-serious adverse events, sexual functioning, and laboratory tests of blood and urine. There were few significant between-group differences in sexual functioning or for most laboratory analyses, with only small differences observed in changes over time in total bilirubin, potassium, and the incidence of glucosuria (elevated glucose in the urine). Thus, there does not appear to be any evidence for serious toxicity of saw palmetto. However, the sample size and length of the study does not rule out potential rare adverse effects associated with the use of saw palmetto.

One of the actions of saw palmetto is the inhibition of the enzyme 5-α-reductase which is involved in the conversion of testosterone to dihydrotesterone (see The Medical Biochemistry Page for details), thus it has anti-androgenic effects and possibly explains the therapeutic effects against BPH and related lower urinary-tract symptoms. In studies in rats, saw palmetto extracts were shown to actively bind alpha(1)-adrenergic (α1-adrenergic), muscarinic and 1,4-dihydropyridine calcium channel (1,4-DHP) receptors in the prostate and bladder. When the lipid fraction of saw palmetto extracts were assayed in this system it was found that oleic and lauric acids (fatty acids) were the active components. Oleic and lauric acids were also shown to inhibit 5-α-reductase. Additional studies have shown that in addition to oleic and lauric acids, myristic acid and linoleic acid bind to the same receptors and also inhibited 5α-reductase activity.

Saw palmetto also exhibits anti-proliferative and anti-inflammatory effects. The anti-inflammatory actions of saw palmetto are attributed to the lipido-sterolic extract of the fruit and beta-sitosterol, the glycoside (sugar containing) of the extract. An additional component of the lipido-sterolic extract of saw palmetto is stigmasterol. These compounds are collectively referred to as phytosterols. An additional phytosterol is campesterol.

In a study of inflammatory responses in hair follicle cells in culture, the lipido-sterolic extract of saw palmetto was able to suppress the inflammation-induced expression of several pro-inflammatory cytokines (growth factor proteins that stimulate inflammatory responses). This study was undertaken to determine the ability of saw palmetto extracts to inhibit hair follicle inflammation which is a significant contributing factor in androgenic alopecia, hair loss due to high dihydrotestosterone levels. Thus, 5-α reductase inhibition combined with blockade of inflammatory processes effected by saw palmetto extracts could represent a novel two-pronged approach in the treatment of this hair loss disorder.

The anti-inflammatory actions of beta-sitosterol explain, in part, observations that the compound can inhibit prostate cancer cell growth in culture. In one study it was shown that saw palmetto extracts that contained beta-sitosterol and stigmasterol inhibited prostate cancer cell growth by activating the expression of the tumor suppressor gene P53 (for more information of P53 see The Medical Biochemistry Page). Beta-sitosterol exerts anti-cancer actions on other types of cancer cells as well. Treatment of human stomach cancer cells in culture with beta-sitosterol activates apoptotic (programmed cell death) pathways resulting in killing of the cells.

Beta-sitosterol has also been shown to be beneficial for lowering serum cholesterol levels. Numerous human clinical studies have confirmed the efficacy of beta-sitosterol in lowering plasma LDL concentrations and animal studies have also shown reductions in LDL by beta-sitosterol. The understanding of the function of plant sterols such as beta-sitosterol in impeding cholesterol absorption has been clarified with the discovery of the ATP-binding cassette transporters, ABCG5 and ABCG8, involved in the regulation of sterol absorption and secretion into the enterocyte (absorptive cells of the intestine) and hepatocyte (liver cells). ABCG5 and ABCG8 function as a complex working together to transport sterols. For more information on ABC transporters see The Medical Biochemistry Page. Compared to cholesterol and other sterols, beta-sitosterol is preferentially taken up by the intestinal lumen via the actions of the ABCG5/8 transporters. This selective binding of beta-sitosterol to the transporters ultimately results in significant lowering of plasma cholesterol due to a reduction in intestinal uptake.

Scholtysek C, Krukiewicz AA, Alonso JL, Sharma KP, Sharma PC, and Goldmann WH 2009. Characterizing components of the Saw Palmetto Berry Extract (SPBE) on prostate cancer cell growth and traction. Biochem. Biophys. Res. Commun. 379(3):795-798.

Zhao Y, Chang SK, Qu G, Li T, and Cui H 2009. Beta-sitosterol inhibits cell growth and induces apoptosis in SGC-7901 human stomach cancer cells. J. Agric. Food Chem. 57(12):5211-5218.

Fernandez ML, and Vega-López S 2005. Efficacy and safety of sitosterol in the management of blood cholesterol levels. Cardiovasc. Drug Rev. 23(1):57-70.

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St John's wort (Hypericum perforatum): The name St. John's wort apparently refers to John the Baptist, as the plant blooms around the time of the feast of St. John the Baptist in late June. St John's wort has been used as an herbal supplement for centuries. It was originally used to treat nerve pain and mental disorders. It has also been used as a sedative and a treatment for malaria, and as a balm for wounds, burns, and insect bites. Recent usage of the herb has been focused on its purported effectiveness at treating depression, anxiety, and sleep disorders. St John's wort contains numerous bioactive compounds with the naphthodianthrones, hypericin and hyperforin being the two most often suggested to be responsible for the effects of the herb.

Hypericins and their derivatives have been extensively studied mainly for their antitumor, antiviral and antidepressant properties. Notably, hypericin is one of the most potent naturally occurring photodynamic agents. It is able to generate the superoxide anion that is considered to be primarily responsible for its biological effects. The pro-oxidant photodynamic properties of hypericin have been exploited for the photodynamic therapy of cancer (PDT). Hypericin, in combination with light, very effectively induces apoptosis and/or necrosis of cancer cells. The mechanism by which these activities are expressed is a continuing area of study. Different modes of action including generation of reactive oxygen species (ROS), antiangiogenesis, immune responses and multiple molecular pathways possibly interacting have been implicated.

Current clinically controlled studies do not support the use of St John's wort in the treatment of major depression. A study co-funded by the National Center for Complementary and Alternative Medicine (NCCAM) found that St. John's wort was no more effective than placebo in treating major depression of moderate severity. There is some scientific evidence that St. John's wort is useful in ameliorating symptoms of milder forms of depression.

Persons taking St John's wort should be aware that several clinical trials have shown that compounds in the herbal supplement can affect the bioavailability of numerous prescription medications. Thus, it is strongly advised that individuals consult their physician prior to consuming supplements containing St John's wort. Ingestion of St Joh's wort results in the induction of two enzymatic pathways in the liver involved in drug (xenobiotics) clearance. These enzymes are of the cytochrome P450 (CYP) family and the P-glycoprotein family. Some of the drugs whose plasma concentrations are reduced and/or clearance rates are increased (thus resulting in a reduced effective concentration of the drug) by consumption of St John's wort include: alprazolam (Xanax, Xanor, Alprax, Niravam: treatment of anxiety), amitriptyline (Elavil, Tryptizol, Laroxyl, Sarotex: a tricyclic antidepressant), atorvastatin (Lipitor: treatment for hypercholesterolemia), chlorzoxazone (Paraflex, Parafon Forte, Relaxazone, Remular-S: treatment of muscle spasms), ciclosporin (Cyclosporin: immunosuppressant used by organ transplant patients), debrisoquine (a guanidine derivative for treatment of hypertension), digoxin (Lanoxin, also known as digitalis: treatment of congestive heart failure, CHF), erythromycin (E-Mycin, Eryc, Ery-Tab, PCE, Pediazole, Ilosone: antibiotic used in upper and lower respiratory infections), fexofenadine (Allegra, Telfast, Fastofen, Tilfur: antihistamine for hay fever and allergy treatment), gliclazide (Glipizide: oral type 2 diabetes drug for lowering blood glucose), imatinib (Gleevec: chemotherapeutic for Philadelphia chromosome positive chronic myelogenous leukemia), indinavir (Crixivan: a protease inhibitor used as a component of highly active antiretroviral therapy, HAART), irinotecan (Camptosar: a topoisomerase I inhibitor used as chemotherapy drug for colo-rectal cancer), ivabradine (Procoralan: management of stable angina pectoris), mephenytoin (Mesantoin: an anticonvulsant), methadone (Symoron, Dolophine, Amidone, Methadose, Physeptone, Heptadon: synthetic opioid used to treat narcotic dependence and withdrawal), midazolam (Versed, Dormicum, Hypnovel: short acting injected sleep inducer for surgery, also produces amnesia) nifedipine (Adalat, Nifedical, Procardia: treatment of hypertension), omeprazole (Prilosec, Zegerid: proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease, PUD, and gastroesophageal reflux disorder, GERD), oral contraceptives, quazepam (Doral, Dormalin: treatment of insomnia), simvastatin (Zocor: treatment for hypercholesterolemia), tacrolimus (FK-506 or Fujimycin: immunosuppressant used by organ transplant patients), verapamil (Isoptin, Verelan, Verelan PM, Calan, Bosoptin, Covera-HS: L-type calcium channel blocker for treatment of hypertension), voricoazole (VFEND: antifungal medication), and warfarin (Coumadin, Jantoven, Marevan, Lawarin, Waran: anticoagulant).

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Tongkat Ali (Eurycoma longifolia Jack): Eurycoma longifolia Jack is an herbal medicinal plant of South-East Asian origin, popularly recognized as Tongkat Ali. The plant parts have been traditionally used for its antimalarial, aphrodisiac, anti-diabetic, antimicrobial and anti-pyretic activities, which have also been demonstrated scientifically. Tongkat Ali is also thought to enhance male fertility with regard to higher semen volumes, sperm concentrations, the percentage of normal sperm morphology and sperm motility. Several herbal supplement preparations marketed for their purported ability to aid erectile dysfunction contain Tongkat Ali. The plant parts are rich in various bioactive compounds (like eurycomaoside, eurycolactone, eurycomalactone, eurycomanone, and pasakbumin-B) among which the alkaloids and quassinoids form a major portion.

A treatment protocol using a proprietary standardized, water-soluble extract of the root of Eurycoma longifolia Jack has shown improvement in semen counts. A total of 350 patients were given 200mg of the extract daily and follow-up semen analyses were performed every 3 months for 9 months. Of these 350 patients, 75 patients completed one full cycle of 3 months. Follow-up semen analyses in these patients showed significant improvement in all semen parameters.

Tongkat Ali has also been studied for its efficacy in the treatment of erectile dysfunction (ED). A relatively new herbal combination supplement marketed for the treatment of ED, called Etana, contains Tongkat ali. In addition to Tangkat Ali, Etana contains three additional herbal extracts including Panax quinquelotius (Ginseng), Epimedium grandiflorum (Horny goat weed), Centella asiatica (Gotu Kola). In a study using male rats, the effects of Etana administration were monitored by assessing penile erection, genital grooming and copulation mounting. When compared with sildenafil citrate (Viagra®), Etana induced more pronounced penile erections. It is important to point out that the effects of Etana on erectile function are due to the entire herbal combination since any single herbal supplement alone, or any combination of two of the herbal components of Etana did not produce efficacious results. The results of this study indicate that this is a safe combination of herbal components that enhance erectile function.

Bhat R, and Karim AA 2010. Tongkat Ali (Eurycoma longifolia Jack): A review on its ethnobotany and pharmacological importance. Fitoterapia Epub ahead of print.

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Tribulus terrestris: Tribulus terrestris is a flowering plant (family Zygophyllaceae) that is native to warm temperate and tropical regions of southern Europe and southern Asia, as well as throughout Africa and Australia. Dietary supplements containing Tribulus extracts are purported to be useful for enhancing athletic performance. Several herbal supplement preparations marketed for their purported ability to aid erectile dysfunction contain Tribulus extracts. Although it is marketed as being able to increase the levels of testosterone in males, there is conflicting scientific evidence on the androgenic effects for supplements made from Tribulus terrestris.

Comprehensive review of tribulus supplements

Hormonal effects of Tribulus have been evaluated in primates, rabbits and rats to identify its usefulness in the management of erectile dysfunction (ED). In one study Tribulus extracts were administered intravenously at various concentrations using a single injection (in primates) or the extracts were given to rabbits and rats orally at various doses for 8 weeks. An additional test was carried out in this study in which castrated rats were treated with either testosterone cypionate subcutaneously twice a week for 8 weeks or fed Tribulus extracts for 8 weeks. Blood samples in all animals were analyzed for levels of testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone sulphate (DHEAS). In primates, the increases in testosterone (52%), DHT (31%) and DHEAS (29%) were statistically significant. In rabbits, both testosterone and DHT were increased compared to control, however, only the increases in DHT were statistically significant. In the castrated rats, increases in testosterone levels were observed that were statistically significant. This study showed that consumption of Tribulus extracts may result in increases in some of the androgenic hormones, possibly due to the presence of protodioscin in the extract. Thus, Tribulus extracts may be useful in mild to moderate cases of ED.

In another study examining the androgenic effects of Tribulus extracts castrated male and female rats were administered three different doses of Tribulus extract for 28 days. In addition to Tribulus extract administration there was a group of castrated animals treated with dehydroepiandrosterone (DHEA). Additionally, animals in this study were given testosterone (males) and 17α-ethynylestradiol (females) as positive controls for androgenicity and estrogenicity, respectively. The results of this particular study demonstrated that neither DHEA nor Tribulus extract was able to stimulate androgen sensitive tissues like the prostate and seminal vesicle in both intact and castrated male rats. In addition, administration of Tribulus extract to intact male rats for 28 days did not change serum testosterone levels nor was the administration able produce any quantitative change in the fecal excretion of androgenic metabolites. Tribulus was not able to stimulate endocrine sensitive tissues such as the prostate, seminal vesicle, uterus and vagina in this study indicating a lack of androgenic and estrogenic activity in vivo. Although this study found a positive effect of Tribulus on the level of sperm production there were no associated changes in the levels of circulating androgens.

Some evidence indicates that Tribulus consumption may be useful in lowering serum cholesterol levels and the cardiovascular damage associated with hypercholesterolemia. A recent study examined the effects of Tribulus extracts on the lipid profile and vascular endothelium of the abdominal aorta in New Zealand rabbits fed a cholesterol-rich diet. The rabbits were randomly divided into three groups. One experimental group was given a cholesterol-rich diet, a second experimental group was treated with Tribulus extract along with the cholesterol-rich diet, and a control group was fed a standard diet. Blood samples were collected at the start of the experiment and then at weeks 4 and 12 to determine total serum cholesterol, high density lipoprotein-associated cholesterol (HDL-C), low density lipoprotein-associated cholesterol (LDL-C) and triglyceride levels. In animals treated with Tribulus, the serum lipid profiles were significantly lower than those fed a high cholesterol diet without Tribulus at week 12 with a reduction of all lipids tested. Lipid profiles in the Tribulus treated rabbits averaged 50% of the levels of the high cholesterol alone fed rabbits. Examination of the vessels in the Tribulus treated rabbits revealed that endothelial damage was less than in the rabbits that were not fed the herbal supplement. These data indicate that dietary intake of Tribulus can significantly lower serum lipid profiles, decrease endothelial cellular surface damage and rupture and may partially repair the endothelial dysfunction resulting from hyperlipidemia.

Accumulating evidence suggests that extracts from Tribulus terrestris exhibit antimicrobial activity. The antimicrobial activity of organic and aqueous extracts from the fruits, leaves and roots of Tribulus have been examined against 11 species of pathogenic and non-pathogenic microorganisms. The micororganisms tested were Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Corynebacterium diphtheriae, Escherichia coli, Proteus vulgaris, Serratia marcescens, Salmonella typhimurium, Klebsiella pneumoniae, Pseudomonas aeruginosa and Candida albicans. The results of this study demonstrated that extracts from each of the different parts of the plant showed antimicrobial activity against most tested microorganisms. The most active extract against both Gram-negative and Gram-positive bacteria was the ethanolic extract from the fruits with highest efficacy against B. subtilis, B. cereus, P. vulgaris and C. diphtheriae. In addition, the same ethanolic extract from fruit of Tribulus demonstrated the strongest antifungal activity against C. albicans.

Tuncer MA, Yaymaci B, Sati L, Cayli S, Acar G, Altug T, and Demir R 2009. Influence of Tribulus terrestris extract on lipid profile and endothelial structure in developing atherosclerotic lesions in the aorta of rabbits on a high-cholesterol diet. Acta Histochem. 111(6):488-500.

Gauthaman K, and Ganesan AP 2008. The hormonal effects of Tribulus terrestris and its role in the management of male erectile dysfunction--an evaluation using primates, rabbit and rat. Phytomedicine. 15(1-2):44-54.

Neychev VK, and Mitev VI 2005. The aphrodisiac herb Tribulus terrestris does not influence the androgen production in young men. J. Ethnopharmacol. 101(1-3):319-323.

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Turmeric (Curcuma longa): Turmeric is derived from the rhizomes (the horizontal stem of a plant found underground: picture the ginger root you find in the grocery store) of the perennial herb, Curcuma longa Linn, which is a member of the ginger family (Zingerberaceae). Curcumin is the yellow compound found in turmeric. For a more complete description of the activities of curcumin see the Antioxidants page.

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Uva ursi (Arctostaphylos uva ursi): Uva ursi is an evergreen shrub that produces red berries and flourishes in alpine forests in many regions, including North America, Europe, the Iberian Peninsula, Siberia, and the Himalayas. Uva ursi is also known as bearberry because bears like eating the fruit. Only the leaves of the plant, and not the berries, are used for medicinal purposes.

Native Americans used uva ursi as a remedy for urinary tract infections and until the discovery of sulfa drugs and related antibiotics, uva ursi was a common treatment for bladder and related infections. The antibacterial properties of uva ursi are due to several chemicals including arbutin and hydroquinone. Other bioactive compounds in uva ursi are tannins that have astringent effects helping to shrink and tighten mucous membranes in the body which helps to reduce inflammation and fight infection. Current herbal supplement uses for uva ursi are in the treatment of urinary tract infections and cystitis (bladder inflammation) where it appears to be most effective when consumed at the first sign of infection. Controlled clinical studies are needed to verify if indeed uva ursi is effective in humans. It is also important to note that uva ursi can be toxic since hydroquinone can cause serious liver damage.

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Valerian root (Valeriana officinalis): Valerian is a member of the Valerianaceae family which is a perennial plant native to Europe and Asia and that has been naturalized in North America. Valerian has been used as a medicinal herb for thousands of years, first appearing in the literature of ancient Greece and Rome. In the 18th century it was used to treat nervousness, trembling, headaches, and heart palpitations. Interestingly, in the mid-19th century valerian was considered a stimulant that caused some of the same complaints it was thought to treat and, therefore, was not considered a useful medicinal herb. Valerian root extracts contain numerous bioactive compounds including valerenic acids, sesquiterpenes, and valepotriates.

Today valerian root extract is used primarily as supplement for the treatment of insomnia and other sleep disorders resulting from nervous tension or anxiety. Dried roots are prepared as teas or tinctures and dried plant materials and extracts are put into capsules or incorporated into tablets. In addition to sleep disorders, valerian has been used for gastrointestinal spasms and distress, epileptic seizures, and attention deficit hyperactivity disorder. However, scientific evidence is not sufficient to support the use of valerian for these conditions.

Although the results of some clinical studies have suggested that valerian may be useful for insomnia and other sleep disorders, results of other studies do not. Interpretation of the results of many studies is complicated by the fact the studies had small sample sizes, used different amounts and sources of valerian, measured different outcomes, or did not consider potential bias resulting from high participant withdrawal rates. Overall, the evidence from most controlled clinical trials for the sleep-promoting effects of valerian is inconclusive.

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Yohimbe (Pausinystalia yohimbe): The yohimbe tree is a tall evergreen that is native to western African and the bark of the tree has been used in traditional African medicine as an aphrodisiac. Yohimbe bark and extracts from the bark contain the chemical yohimbine, an alkaloid that possesses stimulant and aphrodisiac effects.

The amount of yohimbine found in various dietary supplements varies greatly. A standardized form of yohimbine (yohimbine hydrochloride; yohimbine-HCl) is available as a prescription medicine that has been studied and used for the treatment of erectile dysfunction. There is little conclusive clinical evidence of the effects of yohimbe extracts in the form of dietary supplements and the data is further complicated by the fact that various preparations of bark extracts contain vastly different amounts of yohimbine. Although numerous studies of the prescription medicine yohimbine-HCl have been conducted, the results of these studies cannot be interpreted as evidence for the dietary supplement yohimbe.

The consumption of yohimbe extracts has been associated with high blood pressure, increased heart rate, headache, anxiety, dizziness, and sleeplessness. Yohimbe can be dangerous if taken in large doses or for long periods of time. People should use caution if taking yohimbe with monoamine oxidase (MAO) inhibitors or medicines for high blood pressure. Yohimbe should not be combined with tricyclic antidepressants or phenothiazines (medicines used primarily in the treatment of schizophrenia). People with kidney problems and people with psychiatric conditions should not use yohimbe.

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