Download PDF
Planta Med 2013; 79(07): 580-590
DOI: 10.1055/s-0032-1328463
Women's Health
Mini Reviews
Georg Thieme Verlag KG Stuttgart · New York

Phytoestrogenic Potential of Cyclopia Extracts and Polyphenols

Ann Louw
1   Departments of Biochemistry, University of Stellenbosch, Stellenbosch, Matieland, South Africa
,
Elizabeth Joubert
2   Departments of Food Science, University of Stellenbosch, Stellenbosch, Matieland, South Africa
3   Post-Harvest and Wine Technology, ARC (Agricultural Research Council of South Africa) Infruitec-Nietvoorbij, Stellenbosch, South Africa
,
Koch Visser
1   Departments of Biochemistry, University of Stellenbosch, Stellenbosch, Matieland, South Africa
› Author Affiliations
Further Information

Publication History

received 14 December 2012
revised 19 February 2013

accepted 14 March 2013

Publication Date:
22 April 2013 (online)

   Permissions and Reprints

Abstract

Cyclopia Vent. species, commonly known as honeybush, are endemic to Southern Africa. The plant is traditionally used as an herbal tea but several health benefits have recently been recorded. This minireview presents an overview of polyphenols found in Cyclopia and focusses on the phytoestrogenic potential of selected polyphenols and of extracts prepared from the plant.

Key words

Fabaceae - Cyclopia - phytoestrogen - ER binding - ERE promoter reporter assay - E-screen - uterotrophic assay
 

  • References

  • 1 Joubert E, Gelderblom WC, Louw A, de Beer D. South African herbal teas: Aspalathus linearis, Cyclopia spp. and Athrixia phylicoides – a review. J Ethnopharmacol 2008; 119: 376-412
    CrossrefPubMedGoogle Scholar
  • 2 Schutte A. Systematics of the genus Cyclopia Vent. (Fabaceae, Podalyrieae). Edinburgh J Bot 1997; 54: 125-170
    CrossrefPubMedGoogle Scholar
  • 3 Joubert E, Joubert ME, Bester C, de Beer D, De Lange JH. Honeybush (Cyclopia spp.): From local cottage industry to global markets – the catalytic and supporting role of research. S Afr J Bot 2011; 77: 887-907
    CrossrefPubMedGoogle Scholar
  • 4 Watt JM, Breyer-Brandwijk MG. The medicinal and poisonous plants of southern and eastern Africa. London: E. & S. Livingstone; 1962
    Google Scholar
  • 5 Ferreira D, Kamara BI, Brandt EV, Joubert E. Phenolic compounds from Cyclopia intermedia (honeybush tea). 1. J Agric Food Chem 1998; 46: 3406-3410
    CrossrefPubMedGoogle Scholar
  • 6 Kamara BI, Brandt EV, Ferreira D, Joubert E. Polyphenols from honeybush tea (Cyclopia intermedia). J Agric Food Chem 2003; 51: 3874-3879
    CrossrefPubMedGoogle Scholar
  • 7 Kamara BI, Brand DJ, Brandt EV, Joubert E. Phenolic metabolites from honeybush tea (Cyclopia subternata). J Agric Food Chem 2004; 52: 5391-5395
    CrossrefPubMedGoogle Scholar
  • 8 Joubert E, Richards ES, Van der Merwe JD, De Beer D, Manley M, Gelderblom WC. An effect of species variation and processing on phenolic composition and in vitro antioxidant activity of aqueous extracts of Cyclopia spp. (honeybush tea). J Agric Food Chem 2008; 56: 954-963
    CrossrefPubMedGoogle Scholar
  • 9 Hubbe ME. Evaluation of antioxidant and free radical scavenging activities of honeybush tea (Cyclopia). Stellenbosch: Stellenbosch University; 2000
    CrossrefGoogle Scholar
  • 10 Marnewick J, Joubert E, Joseph S, Swanevelder S, Swart P, Gelderblom W. Inhibition of tumour promotion in mouse skin by extracts of rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia), unique South African herbal teas. Cancer Lett 2005; 224: 193-202
    CrossrefPubMedGoogle Scholar
  • 11 Sissing L, Marnewick J, de Kock M, Swanevelder S, Joubert E, Gelderblom W. Modulating effects of rooibos and honeybush herbal teas on the development of esophageal papillomas in rats. Nutr Cancer 2011; 63: 600-610
    CrossrefPubMedGoogle Scholar
  • 12 Muller CJF, Joubert E, Gabuza K, de Beer D, Louw J, Fey SJ. Assessment of the antidiabetic potential of an aqueous extract of honeybush (Cyclopia intermedia) in streptozotocin and obese insulin resistant wistar rats. In: Rasooli I, ed. Phytochemicals – bioactivities and impact on health. Rijeka: In Tech; 2011: 313-332
    CrossrefGoogle Scholar
  • 13 Mose Larsen P, Fey SJ, Louw J, Joubert L. Anti-diabetic extract of honeybush.. US Patent 20110045108, 2012
    PubMedGoogle Scholar
  • 14 Rood B. Uit die veldapteek. Kaapstad: Tafelberg; 1994
    Google Scholar
  • 15 Kokotkiewicz A, Luczkiewicz M, Sowinski P, Glod D, Gorynski K, Bucinski A. Isolation and structure elucidation of phenolic compounds from Cyclopia subternata Vogel (honeybush) intact plant and in vitro cultures. Food Chem 2012; 133: 1373-1382
    CrossrefPubMedGoogle Scholar
  • 16 de Beer D, Joubert E. Development of HPLC method for Cyclopia subternata phenolic compound analysis and application to other Cyclopia spp. J Food Comp Anal 2010; 23: 289-297
    CrossrefPubMedGoogle Scholar
  • 17 De Beer D, Schulze AS, Joubert E, De Villiers A, Malherbe CJ, Stander MA. Food ingredient extracts of Cyclopia subternata (honeybush): variation in phenolic composition and antioxidant capacity. Molecules 2012; 17: 14602-14624
    CrossrefPubMedGoogle Scholar
  • 18 Hattori M, Shu YZ, El-Sedawy AI, Namba T, Kobashi K, Tomimori T. Metabolism of homoorientin by human intestinal bacteria. J Nat Prod 1988; 51: 874-878
    CrossrefPubMedGoogle Scholar
  • 19 Sanugul K, Akao T, Li Y, Kakiuchi N, Nakamura N, Hattori M. Isolation of a human intestinal bacterium that transforms mangiferin to norathyriol and inducibility of the enzyme that cleaves a C-glucosyl bond. Biol Pharm Bull 2005; 28: 1672-1678
    CrossrefPubMedGoogle Scholar
  • 20 Nakamura K, Nishihata T, Jin JS, Ma CM, Komatsu K, Iwashima M, Hattori M. The C-glucosyl bond of puerarin was cleaved hydrolytically by a human intestinal bacterium strain PUE to yield its aglycone daidzein and an intact glucose. Chem Pharm Bull (Tokyo) 2011; 59: 23-27
    CrossrefPubMedGoogle Scholar
  • 21 Shanle EK, Xu W. Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action. Chem Res Toxicol 2011; 24: 6-19
    CrossrefPubMedGoogle Scholar
  • 22 Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, Tujague M, Strom A, Treuter E, Warner M, Gustafsson JA. Estrogen receptors: how do they signal and what are their targets. Physiol Rev 2007; 87: 905-931
    CrossrefPubMedGoogle Scholar
  • 23 Kortenkamp A, Martin O, Faust M, Evans R, McKinley R, Orton F, Rosivatz E. State of the art assessment of endocrine disruptors. Final Rep 2011; 2011: 1-135
    PubMedGoogle Scholar
  • 24 EDSTAC. Endocrine disruptor screening and testing advisory committee final report, 1998. Washington: US Environmental Protection Agency; 1998
    CrossrefGoogle Scholar
  • 25 Saarinen NM, Bingham C, Lorenzetti S, Mortensen A, Makela S, Penttinen P, Sorensen IK, Valsta LM, Virgili F, Vollmer G, Warri A, Zierau O. Tools to evaluate estrogenic potency of dietary phytoestrogens: a consensus paper from the EU Thematic Network “Phytohealth” (QLKI-2002–2453). Genes Nutr 2006; 1: 143-158
    CrossrefPubMedGoogle Scholar
  • 26 Soto AM, Maffini MV, Schaeberle CM, Sonnenschein C. Strengths and weaknesses of in vitro assays for estrogenic and androgenic activity. Best Pract Res Clin Endocrinol Metab 2006; 20: 15-33
    CrossrefPubMedGoogle Scholar
  • 27 Dobbins LL, Brain RA, Brooks BW. Comparison of the sensitivities of common in vitro and in vivo assays of estrogenic activity: application of chemical toxicity distributions. Environ Toxicol Chem 2008; 27: 2608-2616
    CrossrefPubMedGoogle Scholar
  • 28 Fang H, Tong W, Perkins R, Soto AM, Prechtl NV, Sheehan DM. Quantitative comparisons of in vitro assays for estrogenic activities. Environ Health Perspect 2000; 108: 723-729
    CrossrefPubMedGoogle Scholar
  • 29 Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol 2010; 31: 400-419
    CrossrefPubMedGoogle Scholar
  • 30 Verhoog NJD, Joubert E, Louw A. Screening of four Cyclopia (honeybush) species for putative phyto-oestrogenic activity by oestrogen receptor binding assays. S Afr J Sci 2007; 103: 13-21
    PubMedGoogle Scholar
  • 31 de Cremoux P, This P, Leclercq G, Jacquot Y. Controversies concerning the use of phytoestrogens in menopause management: bioavailability and metabolism. Maturitas 2010; 65: 334-339
    CrossrefPubMedGoogle Scholar
  • 32 Verhoog NJ, Joubert E, Louw A. Evaluation of the phytoestrogenic activity of Cyclopia genistoides (honeybush) methanol extracts and relevant polyphenols. J Agric Food Chem 2007; 55: 4371-4381
    CrossrefPubMedGoogle Scholar
  • 33 Liu L, Xu DM, Cheng YY. Distinct effects of naringenin and hesperetin on nitric oxide production from endothelial cells. J Agric Food Chem 2008; 56: 824-829
    CrossrefPubMedGoogle Scholar
  • 34 Promberger A, Dornstauder E, Frühwirth C, Schmid ER, Jungbauer A. Determination of estrogenic activity in beer by biological and chemical means. J Agric Food Chem 2001; 49: 633-640
    CrossrefPubMedGoogle Scholar
  • 35 Guo D, Wang J, Wang X, Luo H, Zhang H, Cao D, Chen L, Huang N. Double directional adjusting estrogenic effect of naringin from Rhizoma drynariae (Gusuibu). J Ethnopharmacol 2011; 138: 451-457
    CrossrefPubMedGoogle Scholar
  • 36 Breinholt V, Larsen JC. Detection of weak estrogenic flavonoids using a recombinant yeast strain and a modified MCF7 cell proliferation assay. Chem Res Toxicol 1998; 11: 622-629
    CrossrefPubMedGoogle Scholar
  • 37 Han DH, Denison MS, Tachibana H, Yamada K. Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids. Biosci Biotechnol Biochem 2002; 66: 1479-1487
    CrossrefPubMedGoogle Scholar
  • 38 Reiter E, Beck V, Medjakovic S, Mueller M, Jungbauer A. Comparison of hormonal activity of isoflavone-containing supplements used to treat menopausal complaints. Menopause 2009; 16: 1049-1060
    CrossrefPubMedGoogle Scholar
  • 39 Tang JY, Li S, Li ZH, Zhang ZJ, Hu G, Cheang LC, Alex D, Hoi MP, Kwan YW, Chan SW, Leung GP, Lee SM. Calycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVEC. PLoS One 2010; 5: e11822
    CrossrefPubMedGoogle Scholar
  • 40 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 2003; 84: 259-268
    CrossrefPubMedGoogle Scholar
  • 41 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; 16: 314-319
    CrossrefPubMedGoogle Scholar
  • 42 Chen J, Liu L, Hou R, Shao Z, Wu Y, Chen X, Zhou L. Calycosin promotes proliferation of estrogen receptor-positive cells via estrogen receptors and ERK1/2 activation in vitro and in vivo . Cancer Lett 2011; 308: 144-151
    CrossrefPubMedGoogle Scholar
  • 43 Zhu JT, Choi RC, Chu GK, Cheung AW, Gao QT, Li J, Jiang ZY, Dong TT, Tsim KW. Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: a comparison of different flavonoids in activating estrogenic effect and in preventing beta-amyloid-induced cell death. J Agric Food Chem 2007; 55: 2438-2445
    CrossrefPubMedGoogle Scholar
  • 44 Mfenyana C, De Beer D, Joubert E, Louw A. Selective extraction of Cyclopia for enhanced in vitro phytoestrogenicity and benchmarking against commercial phytoestrogen extracts. J Steroid Biochem Mol Biol 2008; 112: 74-86
    CrossrefPubMedGoogle Scholar
  • 45 Kitalong C, El-Halawany A, El-Dine R, Ma C, Hattori M. Phenolics from Phaleria nisidai with estrogenic activity. Records Nat Prod 2012; 6: 296-300
    PubMedGoogle Scholar
  • 46 Collins-Burow BM, Burow ME, Duong BN, McLachlan JA. Estrogenic and antiestrogenic activities of flavonoid phytochemicals through estrogen receptor binding-dependent and -independent mechanisms. Nutr Cancer 2000; 38: 229-244
    CrossrefPubMedGoogle Scholar
  • 47 Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 2009; 16: 97-110
    CrossrefPubMedGoogle Scholar
  • 48 Geller SE, Studee L. Botanical and dietary supplements for menopausal symptoms: what works, what does not. J Womens Health (Larchmt) 2005; 14: 634-649
    CrossrefPubMedGoogle Scholar
  • 49 Nilsson S, Mäkelä S, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Pettersson K, Warner M, Gustafsson JÅ. Mechanisms of estrogen action. Physiol Rev 2001; 81: 1535-1565
    PubMedGoogle Scholar
  • 50 Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med 2006; 354: 270-282
    CrossrefPubMedGoogle Scholar
  • 51 Humphries KH, Gill S. Risks and benefits of hormone replacement therapy: the evidence speaks. Can Med Assoc J 2003; 168: 1001-1010
    PubMedGoogle Scholar
  • 52 Rymer J, Wilson R, Ballard K. Making decisions about hormone replacement therapy. Br Med J 2003; 326: 322-326
    CrossrefPubMedGoogle Scholar
  • 53 Glazier MG, Bowman MA. A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy. Arch Intern Med 2001; 161: 1161-1172
    CrossrefPubMedGoogle Scholar
  • 54 Rossouw J, Anderson G, Prentice R, LaCroix AZ, Kooperberg C, Stefanick M, Jackson RD, Beresford SA, Howard BV, Johnson KC. Writing Group for the Womenʼs Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Womenʼs Health Initiative randomized controlled trial. JAMA 2002; 288: 321-333
    CrossrefPubMedGoogle Scholar
  • 55 Farquhar D. Postmenopausal hormone replacement therapy for chronic disease prevention: results from the Womenʼs Health Initiative trial. CMAJ 2002; 167: 377-378
    PubMedGoogle Scholar
  • 56 Van Leeuwen FE, Rookus MA. Breast cancer and hormone-replacement therapy: the Million Women Study. The Lancet 2003; 362: 1330
    CrossrefPubMedGoogle Scholar
  • 57 Warren MP, Halpert S. Hormone replacement therapy: controversies, pros and cons. Best Pract Res Clin Endocrinol Metab 2004; 18: 317-332
    CrossrefPubMedGoogle Scholar
  • 58 Santen RJ, Allred DC, Ardoin SP, Archer DF, Boyd N, Braunstein GD, Burger HG, Colditz GA, Davis SR, Gambacciani M. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010; 95: s1-s66
    CrossrefPubMedGoogle Scholar
  • 59 Scheiber MD, Rebar RW. Isoflavones and postmenopausal bone health: a viable alternative to estrogen therapy?. Menopause 1999; 6: 233
    CrossrefPubMedGoogle Scholar
  • 60 Russell L, Hicks GS, Low AK, Shepherd JM, Brown CA. Phytoestrogens: a viable option?. Am J Med Sci 2002; 324: 185-188
    CrossrefPubMedGoogle Scholar
  • 61 Mackey R, Eden J. Phytoestrogens and the menopause. Climacteric 1998; 1: 302-308
    CrossrefPubMedGoogle Scholar
  • 62 Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med 1997; 29: 95-120
    CrossrefPubMedGoogle Scholar
  • 63 Magee PJ, Rowland IR. Phytoestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr 2004; 91: 513-531
    CrossrefPubMedGoogle Scholar
  • 64 Amin A, Buratovich M. The anti-cancer charm of flavonoids: a cup-of-tea will do. Recent Pat Anticancer Drug Discov 2007; 2: 109-117
    CrossrefPubMedGoogle Scholar
  • 65 Setchell K. Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr 1998; 68: 1333S-1346S
    CrossrefPubMedGoogle Scholar
  • 66 Palmieri C, Cheng G, Saji S, Zelada-Hedman M, Weihua Z, Van Noorden S, Wahlstrom T, Coombes R, Warner M, Gustafsson J. Estrogen receptor beta in breast cancer. Endocr Relat Cancer 2002; 9: 1-13
    CrossrefPubMedGoogle Scholar
  • 67 Hartman J, Ström A, Gustafsson JÅ. Estrogen receptor beta in breast cancer–diagnostic and therapeutic implications. Steroids 2009; 74: 635-641
    CrossrefPubMedGoogle Scholar
  • 68 Maximov PY, Lee TM, Jordan VC. The discovery and development of Selective Estrogen Receptor Modulators (SERMs) for clinical practice. Curr Clin Pharmacol 2013; 8: 135-155
    CrossrefPubMedGoogle Scholar
  • 69 Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N. Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health. Biotechnol J 2007; 2: 1214-1234
    CrossrefPubMedGoogle Scholar
  • 70 Cornwell T, Cohick W, Raskin I. Dietary phytoestrogens and health. Phytochemistry 2004; 65: 995-1016
    CrossrefPubMedGoogle Scholar
  • 71 Usui T. Pharmaceutical prospects of phytoestrogens. Endocr J 2006; 53: 7-20
    CrossrefPubMedGoogle Scholar
  • 72 Rice S, Whitehead SA. Phytoestrogens oestrogen synthesis and breast cancer. J Steroid Biochem Mol Biol 2008; 108: 186-195
    CrossrefPubMedGoogle Scholar
  • 73 Tempfer CB, Bentz EK, Leodolter S, Tscherne G, Reuss F, Cross HS, Huber JC. Phytoestrogens in clinical practice: a review of the literature. Fertil Steril 2007; 87: 1243-1249
    CrossrefPubMedGoogle Scholar
  • 74 Messina M, Hughes C. Efficacy of soyfoods and soybean isoflavone supplements for alleviating menopausal symptoms is positively related to initial hot flush frequency. J Med Food 2003; 6: 1-11
    CrossrefPubMedGoogle Scholar
  • 75 Boucher BA, Cotterchio M, Anderson LN, Kreiger N, Kirsh VA, Thompson LU. Use of isoflavone supplements is associated with reduced postmenopausal breast cancer risk. Int J Cancer 2013; 132: 1439-1450
    CrossrefPubMedGoogle Scholar
  • 76 Fink BN, Steck SE, Wolff MS, Britton JA, Kabat GC, Gaudet MM, Abrahamson PE, Bell P, Schroeder JC, Teitelbaum SL. Dietary flavonoid intake and breast cancer survival among women on Long Island. Cancer Epidemiol Biomarkers Prev 2007; 16: 2285-2292
    CrossrefPubMedGoogle Scholar
  • 77 Wu A, Yu M, Tseng C, Pike M. Epidemiology of soy exposures and breast cancer risk. Br J Cancer 2008; 98: 9-14
    CrossrefPubMedGoogle Scholar
  • 78 Shu XO, Zheng Y, Cai H, Gu K, Chen Z, Zheng W, Lu W. Soy food intake and breast cancer survival. JAMA 2009; 302: 2437-2443
    CrossrefPubMedGoogle Scholar
  • 79 Lee SA, Shu XO, Li H, Yang G, Cai H, Wen W, Ji BT, Gao J, Gao YT, Zheng W. Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Womenʼs Health Study. Am J Clin Nutr 2009; 89: 1920-1926
    CrossrefPubMedGoogle Scholar
  • 80 Travis RC, Allen NE, Appleby PN, Spencer EA, Roddam AW, Key TJ. A prospective study of vegetarianism and isoflavone intake in relation to breast cancer risk in British women. Int J Cancer 2008; 122: 705-710
    CrossrefPubMedGoogle Scholar
  • 81 Hooper L, Madhavan G, Tice JA, Leinster SJ, Cassidy A. Effects of isoflavones on breast density in pre- and post-menopausal women: a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update 2010; 16: 745-760
    CrossrefPubMedGoogle Scholar
  • 82 Mersereau JE, Levy N, Staub RE, Baggett S, Zogric T, Chow S, Ricke WA, Tagliaferri M, Cohen I, Bjeldanes LF. Liquiritigenin is a plant-derived highly selective estrogen receptor β agonist. Mol Cell Endocrinol 2008; 283: 49-57
    CrossrefPubMedGoogle Scholar
  • 83 Leitman DC, Christians U. MF101: a multi-component botanical selective estrogen receptor beta modulator for the treatment of menopausal vasomotor symptoms. Expert Opin Investig Drugs 2012; 21: 1031-1042
    CrossrefPubMedGoogle Scholar
  • 84 Rhomberg LR, Goodman JE, Foster WG, Borgert CJ, Van Der Kraak G. A critique of the European Commission Document, “State of the Art Assessment of Endocrine Disrupters”. Crit Rev Toxicol 2012; 42: 465-473
    CrossrefPubMedGoogle Scholar
  • 85 Bock C, Waldmann KH, Ternes W. Mangiferin and hesperidin metabolites are absorbed from the gastrointestinal tract of pigs after oral ingestion of a Cyclopia genistoides (honeybush tea) extract. Nutr Res 2008; 28: 879-891
    CrossrefPubMedGoogle Scholar
  • 86 Bock C, Ternes W. The phenolic acids from bacterial degradation of the mangiferin aglycone are quantified in the feces of pigs after oral ingestion of an extract of Cyclopia genistoides (honeybush tea). Nutr Res 2010; 30: 348-357
    CrossrefPubMedGoogle Scholar
  • 87 Efferth T, Koch E. Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy. Curr Drug Targets 2011; 12: 122-132
    CrossrefPubMedGoogle Scholar
  • 88 Kong DX, Li XJ, Zhang HY. Where is the hope for drug discovery? Let history tell the future. Drug Discov Today 2009; 14: 115-119
    CrossrefPubMedGoogle Scholar
  • 89 Patwardhan B, Mashelkar RA. Traditional medicine-inspired approaches to drug discovery: can Ayurveda show the way forward?. Drug Discov Today 2009; 14: 804-811
    CrossrefPubMedGoogle Scholar
  • 90 Katiyar C, Gupta A, Kanjilal S, Katiyar S. Drug discovery from plant sources: An integrated approach. AYU (An international quarterly journal of research in Ayurveda) 2012; 33: 10-19
    CrossrefPubMedGoogle Scholar
  • 91 Gertsch J. Botanical drugs, synergy, and network pharmacology: forth and back to intelligent mixtures. Planta Med 2011; 77: 1086-1089
    Article in Thieme ConnectPubMedGoogle Scholar
  • 92 Joubert E, Manley M, Maicu C, de Beer D. Effect of pre-drying treatments and storage on color and phenolic composition of green honeybush (Cyclopia subternata) herbal tea. J Agric Food Chem 2010; 58: 338-344
    CrossrefPubMedGoogle Scholar
  • 93 Zava DT, Blen M, Duwe G. Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture. Environ Health Perspect 1997; 105 (Suppl. 03) 637-645
    PubMedGoogle Scholar
  • 94 Zava DT, Duwe G. Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro . Nutr Cancer 1997; 27: 31-40
    CrossrefPubMedGoogle Scholar
  • 95 Hwang SL, Yen GC. Effect of hesperetin against oxidative stress via ER- and TrkA-mediated actions in PC12 cells. J Agric Food Chem 2011; 59: 5779-5785
    CrossrefPubMedGoogle Scholar
  • 96 Lee S, Chung H, Maier CG, Wood AR, Dixon RA, Mabry TJ. Estrogenic Flavonoids from Artemisia vulgaris L. J Agric Food Chem 1998; 46: 3325-3329
    CrossrefPubMedGoogle Scholar
  • 97 Poon CH, Wong TY, Wang Y, Tsuchiya Y, Nakajima M, Yokoi T, Leung LK. The citrus flavanone naringenin suppresses CYP1B1 transactivation through antagonising xenobiotic-responsive element binding. Br J Nutr advance online publication 31 August 2012; DOI: 10.1017/S0007114512003595.
    PubMedGoogle Scholar
  • 98 Zand RS, Jenkins DJ, Diamandis EP. Steroid hormone activity of flavonoids and related compounds. Breast Cancer Res Treat 2000; 62: 35-49
    CrossrefPubMedGoogle Scholar
  • 99 Overk CR, Yao P, Chadwick LR, Nikolic D, Sun Y, Cuendet MA, Deng Y, Hedayat AS, Pauli GF, Farnsworth NR, van Breemen RB, Bolton JL. Comparison of the in vitro estrogenic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense). J Agric Food Chem 2005; 53: 6246-6253
    CrossrefPubMedGoogle Scholar
  • 100 Shemesh M, Lindner HR, Ayalon N. Affinity of rabbit uterine oestradiol receptor for phyto-oestrogens and its use in a competitive protein-binding radioassay for plasma coumestrol. J Reprod Fertil 1972; 29: 1-9
    PubMedGoogle Scholar
  • 101 Ji ZN, Zhao WY, Liao GR, Choi RC, Lo CK, Dong TT, Tsim KW. In vitro estrogenic activity of formononetin by two bioassay systems. Gynecol Endocrinol 2006; 22: 578-584
    CrossrefPubMedGoogle Scholar
  • 102 Matsumoto T, Kobayashi M, Moriwaki T, Kawai S, Watabe S. Survey of estrogenic activity in fish feed by yeast estrogen-screen assay. Comp Biochem Physiol C Toxicol Pharmacol 2004; 139: 147-152
    CrossrefPubMedGoogle Scholar
  • 103 Chemler JA, Lim CG, Daiss JL, Koffas MAG. A versatile microbial system for biosynthesis of novel polyphenols with altered estrogen receptor binding activity. Chem Biol 2010; 17: 392-401
    CrossrefPubMedGoogle Scholar
  • 104 Murata M, Midorikawa K, Koh M, Umezawa K, Kawanishi S. Genistein and daidzein induce cell proliferation and their metabolites cause oxidative DNA damage in relation to isoflavone-induced cancer of estrogen-sensitive organs. Biochemistry 2004; 43: 2569-2577
    CrossrefPubMedGoogle Scholar
  • 105 Sotoca AM, Bovee TFH, Brand W, Velikova N, Boeren S, Murk AJ, Vervoort J, Rietjens IM. Superinduction of estrogen receptor mediated gene expression in luciferase based reporter gene assays is mediated by a post-transcriptional mechanism. J Steroid Biochem Mol Biol 2010; 122: 204-211
    CrossrefPubMedGoogle Scholar
  • 106 Zych M, Folwarczna J, Trzeciak HI. Natural phenolic acids may increase serum estradiol level in ovariectomized rats. Acta Biochim Pol 2009; 56: 503-507
    PubMedGoogle Scholar