Red Clover

Plant Part Used

Flowering tops/heads

Active Constituents

Flavonoid glycosides (including the isoflavones formononetin, daidzein, genistein, biochanin A, and the flavonoid quercetin), coumarins, polysaccharides. (1) [span class=alert]

This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Red clover is a perennial herb, commonly found in Mediterranean and Red Seas countries. It has been used traditionally as a medicinal agent by Asian, European, and Native American cultures as an expectorant, in asthma, and as an alterative (blood purifier) to treat psoriasis, eczema, and other chronic skin conditions. (2)

There has been a great deal of research and reviews on the effects of phytoestrogens (plants that contain chemical entities that have estrogenic activities in the body) as they relate to menopausal symptoms. (3) , (4) Much of this research has been on the use of soy products and its constituents (genistein and daidzein), or the phytoestrogen containing black cohosh (formononetin). (5) , (6) , (7)

Recently, a proprietary extract of red clover, standardized to the phytoestrogen content, has gained a great deal of attention in the management of menopause and related symptoms. Research has focused on the red clover extract, which contains four principle phytoestrogens (biochanin A, fomonontein, genistein, and daidzein), all with reported levels of estrogen-like activity. (8) , (9)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

500mg (standardized extract) daily.

Fluid extract (1:1w/v): 10-30 drops, 3 times daily.

Most Common Dosage

500mg (standardized extract) daily.

Fluid extract (1:1w/v):15 drops, 3 times daily

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 40mg total isoflavones per dose, comprised of the isoflavones genistein (4mg), daidzein (3.5mg), biochanin A (24.5mg), and formononetin (8mg).

Uses

Frequently Reported Uses

  • Phytoestrogenic
  • Menopausal And Postmenopausal Complaints And Imbalances
  • PMS

Other Reported Uses

  • Alterative

Toxicities & Precautions

General

Red clover is reported safe in recommended dosages.

Health Conditions

Red clover contains coumarins. Although no adverse effects related to the coumarins have been reported, large doses may alter the course of therapy in patients with bleeding or clotting disorders. (10)

Pregnancy/ Breast Feeding

Do not use in pregnancy and lactation.

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Red clover contains biochanin A and formononetin which are metabolized to genistein and daidzein, respectively. These isoflavones have been reported alone or in combination to have the following in vitro and in vivo effects:

Estrogenicity – Red clover isoflavones were shown to have oestrogenic effects.(57) They interact with human estrogen receptor sites (11) and their estrogenic effect relative to 17 beta-estradiol is between 1-5 x 10-3. (12)

Opiate activity – Red clover isoflavones were shown to bind with opiate receptors.(58)

Steroidogenesis – Isoflavones modulate a range of enzymes that regulate the production, metabolism, and function of steroidal hormones, including: inhibiting 17 beta-hydroxysteroid dehydrogenase which is involved in the synthesis of 17 beta-estradiol; (13) inhibiting aromatase which converts androstenedione to estrone; (14) and inhibiting 5-alpha-reductase which converts testosterone to dihydrotestosterone. (15) Other activities include inhibition of the oxidation of steroid hormones (16) and the promotion of the production of sex-hormone binding globulin (SHBG) by liver cells. (17)

Antioxidant – Isoflavones are antioxidants as well as promoting the activity of antioxidant enzymes in gut and skin. (18),(19),(59),(60),(61) They also inhibit the oxidation of LDL cholesterol (20),(21),(62) and lipid peroxidation in vivo. (63)

Calcium metabolism and bone turnover – Isoflavones promote calcium storage in cells, and inhibit osteoclast activityand differentiation by increasing apoptosis via caspase 3 pathway. (22) , (23) , (64) They may also maintain bone density, as reported in animal studies. (24),(65) Recent human studies reported that isoflavones from red clover selectively increased cortical bone density of the proximal radius and ulna. (25) , (26)

Cell growth and differentiation – Genistein is an inhibitor of a range of enzymes that modulate cell transduction processes involved in cell growth and differentiation; the principal enzymes are protein tyrosine kinases, and DNA topoisomerases. (27) , (28) , (29) Genistein blocks the growth of normal human lymphocytes and human leukemic cells by arresting growth in the G2/M phase of the cell cycle. (30) Genistein induces terminal differentiation and inhibits proliferation of human and rodent leukemic and melanoma cells and it also induces apoptosis of mouse leukemic cells in vivo. (31) , (32)

Anticancer activity (in vitro) – Isoflavones (mostly genistein) have been reported to be inhibitory in vitro to the following human cell lines: melanoma, (33) leukemia, (34) , (35) breast cancer, (36) , (37) gastrointestinal cancers, (38) , (39) prostate cancer, (40) and neuroblastoma (41) among others.

Anticancer activity (in vivo) – Rodents treated with genistein report increased resistance to chemically induced breast cancer. (42) However, it has not been fully elucidated that taking phytoestrogens containing isoflavones from any source is safe to take if an estrogen-fed cancer is present. Other study assessing the action of isoflavones on rat endometrial cells reported that they did not stimulate cell proliferation.(66) The result was in line with that of human studies which showed no increase in endometrial thickness in postmenopausal women after supplementation of isoflavones. (67)

Cardiovascular effects – Isoflavones exert a wide range of effects on the vasculature, including: inhibition of endothelial cell proliferation; inhibition of chemotaxis and proliferation of vascular smooth muscle cells; promotion of whole cell calcium-activated potassium-channel currents in vascular endothelial cells; inhibition of platelet aggregation; and vasodilation and inhibition of thrombin-evoked calcium entry into smooth muscle cells. (43) , (44) Isoflavones also inhibit nitric oxide production by macrophages and the pro-coagulant activity of activated adherent monocytes. (45) , (46)

Though debated, isoflavones have been reported to decrease serum lipids in vivo and in vitro. (47) A proprietary extract of red clover has been reported to raise HDL cholesterol and decrease ApoB. (48) Authors reported that supplementation with isoflavones did not significantly alter total plasma cholesterol, LDL cholesterol, HDL cholesterol or plasma triglyceride levels levels (49), while others showed a reduction in total cholesterol, LDL cholesterol and triglycerides and an increase in HDL levels. (52) , (68) , (69) Regardless of the impact red clover has on serum lipids, Nestel PJ, et al. suggest that red clover isoflavones reduce cardiovascular risks by reducing arterial elasticity in menopausal women, not by altering serum lipids to any significant extent. (50) Another study evaluated the impact of isoflavones derived from red clover on arterial compliance in 17 women. After a run-in period, a 5-week placebo period was followed by a 5-week period of active treatment with 40 mg of isoflavones and then a 5-week period of active treatment with 80 mg isoflavones. Arterial compliance rose by 23% with the 80-mg isoflavone dose compared to the placebo period. The increase was slightly less with the 40-mg dose. (51)

A meta-analysis on clinical trials reported that red clover isoflavones supplementation produced a marginal significant effect in treating hot flushes symptom. (70) However, this result is in contrast with another systematic review and meta-analysis which reported no significant reduction in hot flushes frequency. (71) The authors suggest that a large placebo response and inadvertent use of dietary isoflavones in the placebo group may have obscured a significant change in flushing frequency. Recently, isoflavones was shown to reduce anxiety and depressive symptoms among postmenopausal women. (72)

Neuroprotective effect (in vitro)- Isoflavones exert neuroprotective effect on human cortical neurons from glutamate toxicity, probably due to their antioxidant and oestrogenic properties. (73) They also protected dopaminergic neurons from lipopolysaccharide-induced damage by inhibiting microglia activation and generation of pro-inflammatory factors.(74) , (75)

The liquid extract of red clover has traditionally been used as an alterative, or as stated above, an agent that “purifies” the blood, removing toxins and improving liver and kidney function, and helping the body maintain homeostasis. (53) Red clover liquid extracts were used routinely by early Eclectic Physicians in conditions such as spasmodic coughs and cancer.

References

  1. View Abstract: Saloniemi H, et al. Phytoestrogen Content and Estrogenic Effect of Legume Fodder. Proc Soc Exp Biol Med. Jan1995;208(1):13-7.
  2. Newall CA, et al. Herbal Medicines: A Guide for Health Care Professionals. London: The Pharmaceutical Press; 1996:227.
  3. View Abstract: Chiechi LM. Dietary Phytoestrogens in the Prevention of Long-term Postmenopausal Diseases. Int J Gynaecol Obstet. Oct1999;67(1):39-40.
  4. View Abstract: Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. May2001;49(5):2472-9.
  5. View Abstract: Seidl MM, et al. Alternative treatments for menopausal symptoms. Systematic review of scientific and lay literature. Can Fam Physician. Jun1998;44:1299-308.
  6. View Abstract: Washburn S, et al. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause. 1999;6(1):7-13.
  7. View Abstract: Lieberman S. A Review of the Effectiveness of Cimicifuga racemosa (black cohosh) for the Symptoms of Menopause. J Womens Health. Jun1998;7(5):525-29.
  8. View Abstract: Knight DC. A review of the clinical effects of phytoestrogens. Obstet Gynecol. May1996;87(5 Pt 2):897-904.
  9. View Abstract: Beck V, Unterrieder E, Krenn L, Kubelka W, Jungbauer A. Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. J Steroid Biochem Mol Biol. Feb2003;84(2-3):259-68.
  10. Newall CA, Anderson LA, Phillipson JD. Herbal Medicines; A Guide for Health-Care Professionals. London:The Pharmaceutical Press;1996.
  11. View Abstract: Collins BM, et al. The estrogenic and antiestrogenic activities of phytochemicals with the human estrogen receptor expressed in yeast. Steroids. Apr1997;62(4):365-72.
  12. View Abstract: Price KR, et al. Naturally occurring estrogens in foods – a review. Food Add Contamin. 1985;2:73-106.
  13. View Abstract: Keung WM. Dietary estrogenic isoflavones are potent inhibitors of beta-hydroxysteroid dehydrogenase of P. testosteronii. Biochem Biophys Res Commun. Oct1995;215(3):1137-44.
  14. View Abstract: Wang C, et al. Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes. J Steroid Biochem Mol Biol. Aug1994;50(3-4):205-12.
  15. View Abstract: Evans BA, et al. Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. J Endocrinol. Nov1995;147(2):295-302.
  16. View Abstract: Keung WM. Dietary estrogenic isoflavones are potent inhibitors of beta-hydroxysteroid dehydrogenase of P. testosteronii. Biochem Biophys Res Commun. Oct1995;215(3):1137-44.
  17. View Abstract: Loukovaara M, et al. Regulation of sex hormone-binding globulin production by isoflavonoids and patterns of isoflavonoid conjugation in HepG2 cell cultures. Steroids. Sep1995;60(9):656-61.
  18. Pratt DE. Antioxidants indigenous to foods. Toxicol Ind Health. Jan1993;9(1-2):63-75.
  19. View Abstract: Vedavanam K, et al. Antioxidant action and potential antidiabetic properties of an isoflavonoid-containing soyabean phytochemical extract (SPE). Phytother Res. Nov1999;13(7):601-8.
  20. View Abstract: Tikkanen MJ, et al. Dietary soy-derived isoflavone phytoestrogens. Could they have a role in coronary heart disease prevention? Biochem Pharmacol. Jul2000;60(1):1-5.
  21. View Abstract: Nestel P, Cehun M, Chronopoulos A, DaSilva L, Teede H, McGrath B. A biochanin-enriched isoflavone from red clover lowers LDL cholesterol in men. Eur J Clin Nutr. Mar2004;58(3):403-8.
  22. View Abstract: Gao YH, et al. Suppressive effect of genistein on rat bone osteoclasts: involvement of protein kinase inhibition and protein tyrosine phosphatase activation. Int J Mol Med. Mar2000;5(3):261-7.
  23. View Abstract: Williams JP, et al. Tyrosine kinase inhibitor effects on avian osteoclastic acid transport. Am J Clin Nutr. Dec1998;68(6 Suppl):1369S-1374S.
  24. View Abstract: Ishimi Y, et al. Selective effects of genistein, a soybean isoflavone, on B-lymphopoiesis and bone loss caused by estrogen deficiency. Endocrinology. Apr1999;140(4):1893-900.
  25. Baber R, et al. The effect of an isoflavone dietary supplement (P-081) on serum lipids, forearm bone density and endometrial thickness in post-menopausal women. NYC: Abstract from NAMS 10th Annual Meeting; Sep1999.
  26. View Abstract: Atkinson C. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. Feb2004;79(2):326-33.
  27. View Abstract: Yoon, et al. Genistein produces reduction in growth and induces apoptosis of rat RPE-J cells. Curr Eye Res. Mar2000;20(3):215-24.
  28. View Abstract: Choi YH, et al. p53-independent induction of p21 (WAF1/CIP1), reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells. Jpn J Cancer Res. Feb2000;91(2):164-73.
  29. View Abstract: Salti GI, et al. Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells. Eur J Cancer. Apr2000;36(6):796-802.
  30. View Abstract: Matsukawa Y, et al. Genistein arrests cell cycle progression at G2-M. Cancer Res. Mar1993;53(6):1328-31.
  31. View Abstract: Kulling SE, et al. The phytoestrogens coumoestrol and genistein induce structural chromosomal aberrations in cultured human peripheral blood lymphocytes. Arch Toxicol. Feb1999;73(1):50-4.
  32. View Abstract: Uckun FM, et al. Treatment of therapy-refractory B-lineage acute lymphoblastic leukemia with an apoptosis-inducing CD19-directed tyrosine kinase inhibitor. Clin Cancer Res. Dec1999;5(12):3906-13.
  33. View Abstract: Hartman RR, et al. Cell differentiation and cell-cycle alterations by tyrosine kinase inhibitors in human melanoma cells. Melanoma Res. Aug1997;7(Suppl 2):S27-33.
  34. View Abstract: Constantinou AL, et al. Inhibition of N-methyl-N-nitrosourea-induced mammary tumors in rats by the soybean isoflavones. Anticancer Res. Nov1996;16(6A):3293-8.
  35. View Abstract: Lamartiniere CA, et al. Genistein studies in rats: potential for breast cancer prevention and reproductive and developmental toxicity. Am J Clin Nutr. Dec1998;68(6 Suppl):1400S-1405S.
  36. View Abstract: Le Bail JC, et al. Effects of phytoestrogens on aromatase, 3beta and 17beta-hydroxysteroid dehydrogenase activities and human breast cancer cells. Life Sci. Feb2000;66(14):1281-91.
  37. View Abstract: Balabhadrapathruni S, et al. Effects of genistein and structurally related phytoestrogens on cell cycle kinetics and apoptosis in MDA-MB-468 human breast cancer cells. Oncol Rep. Jan2000;7(1):3-12.
  38. View Abstract: Iishi H, et al. Genistein attenuates peritoneal metastasis of azoxymethane-induced intestinal adenocarcinomas in Wistar rats. Int J Cancer. May2000;86(3):416-20.
  39. View Abstract: Booth C, et al. Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro. Br J Cancer. Jul1999;80(10):1550-7.
  40. View Abstract: Davis JN, et al. Inhibition of prostate specific antigen expression by genistein in prostate cancer cells. Int J Oncol. Jun2000;16(6):1091-7.
  41. View Abstract: Brown A, et al. Genistein modulates neuroblastoma cell proliferation and differentiation through induction of apoptosis and regulation of tyrosine kinase activity and N-myc expression. Carcinogenesis. Jun1998;19(6):991-7.
  42. View Abstract: Lamartiniere CA, et al. Genistein alters the ontogeny of mammary gland development and protects against chemically-induced mammary cancer in rats. Proc Soc Exp Biol Med. Mar1998;217(3):358-64.
  43. View Abstract: Anthony MS, et al. Effects of soy isoflavones on atherosclerosis: potential mechanisms. Am J Clin Nutr. Dec1998;68(6 Suppl):1390S-1393S.
  44. View Abstract: Deodato B, et al. Cardioprotection by the phytoestrogen genistein in experimental myocardial ischaemia-reperfusion injury. Br J Pharmacol. Dec1999;128(8):1683-90.
  45. View Abstract: Lale A, et al. Ability of different flavonoids to inhibit the procoagulant activity of adherent human monocytes. J Nat Prod. Mar1996;59(3):273-6.
  46. View Abstract: Krol W, et al. Inhibition of nitric oxide (NO.) production in murine macrophages by flavones. Biochem Pharmacol. Sep1995;50(7):1031-5.
  47. View Abstract: Anthony MS, et al. Effects of soy isoflavones on atherosclerosis: potential mechanisms. Am J Clin Nutr. Dec1998;68(6 Suppl):1390S-1393S.
  48. Baber R, et al. The effedt of an isoflavone dietary supplement (P-081) on serum lipids, forearm bone density and endometrial thickness in post-menopausal women. NYC: Abstract from NAMS 10th Annual Meeting; Sep1999.
  49. View Abstract: Howes JB, Sullivan D, Lai N, et al. The Effects of Dietary Supplementation with Isoflavones from Red Clover on the Lipoprotein Profiles of Post Menopausal Women with Mild to Moderate Hypercholesterolaemia. Atherosclerosis. Sep2000;152(1):143-7.
  50. View Abstract: Nestel PJ, et al. Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women. J Clin Endocrinol Metab. Mar1999;84(3):895-8.
  51. View Abstract: Nestel PJ, Pomeroy S, Kay S, Komesaroff P, Behrsing J, Cameron JD, West L. Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women. J Clin Endocrinol Metab. Mar1999;84(3):895-8.
  52. Knight DC, et al. The effect of Promensil, an isoflavone extract, on menopausal symptoms. Climacteric. 1999;2:79-84.
  53. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. 2d ed. New York: John Wiley & Sons; 1996:177-8.
  54. Occhiuto F, Zangla G, Samperi S, Palumbo DR, Pino A, De Pasquale R, Circosta C. The phytoestrogenic isoflavones from Trifolium pratense L. (Red clover) protects human cortical neurons from glutamate toxicity. Phytomedicine. 2008 Sep;15(9):676-82. Epub 2008 Jun 6.
  55. Occhiuto F, Zangla G, Samperi S, Palumbo DR, Pino A, De Pasquale R, Circosta C. The phytoestrogenic isoflavones from Trifolium pratense L. (Red clover) protects human cortical neurons from glutamate toxicity. Phytomedicine. 2008 Sep;15(9):676-82. Epub 2008 Jun 6.
  56. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine. 2000 Jul;7(4):273-82.
  57. Nissan HP, Lu J, Booth NL, Yamamura HI, Farnsworth NR, Wang ZJ. A red clover (Trifolium pratense) phase II clinical extract possesses opiate activity. J Ethnopharmacol. 2007 May 30;112(1):207-10. Epub 2007 Feb 11.
  58. Yu D, Duan Y, Bao Y, Wei C, An L. Isoflavonoids from Astragalus mongholicus protect PC12 cells from toxicity induced by L-glutamate. J Ethnopharmacol. 2005 Apr 8;98(1-2):89-94.
  59. Mu H, Bai YH, Wang ST, Zhu ZM, Zhang YW. Research on antioxidant effects and estrogenic effect of formononetin from Trifolium pratense (red clover). Phytomedicine. 2009 Apr;16(4):314-9. Epub 2008 Aug 30.
  60. Burdette JE, Liu J, Lantvit D, Lim E, Booth N, Bhat KP, Hedayat S, Van Breemen RB, Constantinou AI, Pezzuto JM, Farnsworth NR, Bolton JL. Trifolium pratense (red clover) exhibits estrogenic effects in vivo in ovariectomized Sprague-Dawley rats. J Nutr. 2002 Jan;132(1):27-30.
  61. Rüfer CE, Kulling SE. Antioxidant activity of isoflavones and their major metabolites using different in vitro assays. J Agric Food Chem. 2006 Apr 19;54(8):2926-31.
  62. Mu H, Bai YH, Wang ST, Zhu ZM, Zhang YW. Research on antioxidant effects and estrogenic effect of formononetin from Trifolium pratense (red clover). Phytomedicine. 2009 Apr;16(4):314-9. Epub 2008 Aug 30.
  63. Hwang J, Sevanian A, Hodis HN, Ursini F. Synergistic inhibition of LDL oxidation by phytoestrogens and ascorbic acid. Free Radic Biol Med. 2000 Jul 1;29(1):79-89.
  64. Rassi CM, Lieberherr M, Chaumaz G, Pointillart A, Cournot G. Down-regulation of osteoclast differentiation by daidzein via caspase 3. J Bone Miner Res. 2002 Apr;17(4):630-8.
  65. Kawakita S, Marotta F, Naito Y, Gumaste U, Jain S, Tsuchiya J, Minelli E. Effect of an isoflavones-containing red clover preparation and alkaline supplementation on bone metabolism in ovariectomized rats. Clin Interv Aging. 2009;4:91-100. Epub 2009 May 14.
  66. Alves DL, Lima SM, da Silva CR, Galvão MA, Shanaider A, de Almeida Prado RA, Aoki T. Effects of Trifolium pratense and Cimicifuga racemosa on the endometrium of Wistar rats. Maturitas. 2008 Dec 20;61(4):364-70. Epub 2008 Dec 17.
  67. Imhof M, Gocan A, Reithmayr F, Lipovac M, Schimitzek C, Chedraui P, Huber J. Effects of a red clover extract (MF11RCE) on endometrium and sex hormones in postmenopausal women. Maturitas. 2006 Aug 20;55(1):76-81. Epub 2006 Mar 2.
  68. Hidalgo LA, Chedraui PA, Morocho N, Ross S, San Miguel G. The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled study. Gynecol Endocrinol. 2005 Nov;21(5):257-64.
  69. Terzic MM, Dotlic J, Maricic S, Mihailovic T, Tosic-Race B. Influence of red clover-derived isoflavones on serum lipid profile in postmenopausal women. J Obstet Gynaecol Res. 2009 Dec;35(6):1091-5.
  70. Coon JT, Pittler MH, Ernst E. Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis.Phytomedicine. 2007 Feb;14(2-3):153-9. Epub 2007 Jan 18.
  71. Lethaby AE, Brown J, Marjoribanks J, Kronenberg F, Roberts H, Eden J. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001395.
  72. Lipovac M, Chedraui P, Gruenhut C, Gocan A, Stammler M, Imhof M. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts. Maturitas. 2010 Mar;65(3):258-61. Epub 2009 Nov 30.
  73. Occhiuto F, Zangla G, Samperi S, Palumbo DR, Pino A, De Pasquale R, Circosta C. The phytoestrogenic isoflavones from Trifolium pratense L. (Red clover) protects human cortical neurons from glutamate toxicity. Phytomedicine. 2008 Sep;15(9):676-82. Epub 2008 Jun 6.
  74. Wang X, Chen S, Ma G, Ye M, Lu G. Genistein protects dopaminergic neurons by inhibiting microglial activation. Neuroreport. 2005 Feb 28;16(3):267-70.
  75. Chen HQ, Wang XJ, Jin ZY, Xu XM, Zhao JW, Xie ZJ. Protective effect of isoflavones from Trifolium pratense on dopaminergic neurons. Neurosci Res. 2008;62:123–30.
in this scope
Malaysian Herbal Monograph​
Medicinal Herbs & Plants Monographs​
Traditional Chinese Medicine Herbs (Professional Data)
Herbal Medicines Compendium (HMC) - U.S​