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Molecular screening of Chinese medicinal plants for progestogenic and anti-progestogenic activity

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Abstract

Estrogen and progestins have adverse effects, and many of these adverse effects are caused by progestins. Due to this, many women choose to use botanical alternatives for hormone replacement therapy, which does not trigger steroidogenic properties. Therefore, it is necessary to screen these herbs for progestogenic and anti-progestogenic properties. Extract of 13 Chinese medicinal plants were analysed for progestogenic and anti-progestogenic activities by using progesterone response element-driven luciferase reporter gene bioassay. MTT assay was carried out to investigate the cytotoxic effect of herb extract on PAE cells. Among the 13 herbs, Dipsacus asperoides extract exhibited progestogenic activity, and 10 species – Cortex eucommiae, Folium artemisiae argyi, Glycyrrhiza uralensis, Angelica sinensis, Atractylodes macrocephala koidz, Scutellaria baicalensis, Cuscuta chinensis, Euscaphis japonica, Ailanthus altissima, and Dioscorea opposita – were recognized to have anti-progestogenic like activities. Extract of Dipsacus asperoides demonstrated dose-dependent progestogenic activity, and the progestogenic activity of 100 μg/mL extracts was equivalent to 31.45 ng/mL progesterone activity. Herbs extracts that exhibited anti-progestogenic-like activity also inhibited the 314.46 ng/mL progesterone activity in a dose-response manner. None of the herb extracts shown significant toxic effect on PAE cells at 40–100 μg/mL compared to control. This discovery will aid selection of suitable herbs for hormone replacement therapy.

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References

  • Adams MR, Kaplan JR, Manuck SB, Koritnik DR, Parks JS, Wolfe MS and Clarkson TB 1990 Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys. Lack of an effect of added progesterone. Arterio. Thromb. Vasc. Biol. 10 1051–1057

  • Ahmed HMM, Lin WJ, Yeh JY, Forsberg N, Cheng WTK and Ou BR 2014 Validation of a luciferase bioassay to detect the progestative activity in gilts whose estrus was induced by an uterotonic herb (Ligusticum chuanxiong). Livest. Sci. doi:10.1016/j.livsci.2014.02.012

  • Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW and Toda T 2000 Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am. J. Clin. Nutr. 72 844–852

    CAS  PubMed  Google Scholar 

  • Banno K, Kisu I, Yanokura M, Tsuji K, Masuda K, Ueki A, Kobayashi Y, Yamagami W, et al. 2012 Progestin therapy for endometrial cancer: the potential of fourth-generation progestin (review). Int. J. Oncol. 40 1755–1762

    CAS  PubMed  Google Scholar 

  • Beck V, Rohr U and Jungbauer A 2005 Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy? J. Steroid. Biochemist. Mol. Biol. 94 499–418

    Article  CAS  Google Scholar 

  • Cheung AM, Chaudhry R, Kapral M, Jackevicius C and Robinson G 2004 Perimenopausal and postmenopausal health. MBC. Women Health 4 1472–1474

    Google Scholar 

  • Circosta C, Pasquale RD, Palumbo DR, Samperi S and Occhiuto F 2006 Estrogenic activity of standardized extract of Angelica sinensis. Phytotherapy Res. 20 665–669

  • Cogliano V, Grosse Y, Bann R, Straif K, Secretan B and Ghissassi F 2005 Carcinogenicity of combined oestrogen-progestagen contraceptives and menopausal treatment. Lancet. Oncol. 6 552–563

    Article  PubMed  Google Scholar 

  • Dickerson LM, Pharm D, Mazyck PJ, Pharm D and Hunter MH 2003 Premenstrual Syndrome. Am. Fam. Physician. 67 1743–1752

    PubMed  Google Scholar 

  • Freeman EW, Purdy RH, Coutifaris C, Rickels K and Paul SM 1993 Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers. J. Neuroendocrinol. 58 478–484

    Article  CAS  Google Scholar 

  • Graham JD and Clarke CL 1997 Physiological action of progesterone in target tissues. Endocrin. Rev. 18 502–519

    CAS  Google Scholar 

  • Hammond R and Johnson J 2004 Endometrial hyperplasia. Curr. Obst. Gynaecol. 40 99–103

    Article  Google Scholar 

  • Hazra BG and Pore VS 2001 Mifepristone (RU-486), the recently developed antiprogesterone drug and its analogues. J. Indian Inst. Sci. 81 287–298

  • Hillman JJ, Zuckerman IH and Lee E 2004 The impact of the women's health initiative on hormone replacement therapy in a medicaid program. J. Women Health 213 986–992

    Article  Google Scholar 

  • Jaakkola S, Lyytinen HK, Dyba T, Ylikorkala O and Pukkala E 2010 Endometrial cancer associated with various forms of postmenopausal hormone therapy: a case control study. Int. J. Cancer 1 644–651

  • Jung HW, Jung JK, Son KH, Lee DH, Kang TM, Kim YS, Park YK 2012 Inhibitory effects of the root extract of Dipsacus asperoides on collagen-induced arthritis in mice. J. Ethnopharmacol. 139 98–103

    Article  PubMed  Google Scholar 

  • Kaul A, Nagamani M and Nowicki B 1995 Decreased expression of endometrial decay factor (DAF), a complement regulatory protein, in patients with luteal phase defect. Am. J. Reprod. Immunol. 34 236–240

    Article  CAS  PubMed  Google Scholar 

  • Klein-Hitpass L, Cato AC, Henderson D and Ryffel GU 1991Two types of anti-progestins identified by their differential action in transcriptionally active extracts from T47D cells. Nucleic Acid Res. 19 1227–1234

  • Kreikemeier WM and Mader TL 2004 Effects of growth-promoting agents and season on yearling feedlot heifer performance. J. Anim. Sci. 82 2481–2488

    CAS  PubMed  Google Scholar 

  • Lamberts SW, Koper JW and de Jong FH 1992 Long term treatment with RU486 and glucocorticoid receptor resistance. Theoretical and therapeutic implications. Trends Endocrinol. Metab. 6 199–204

  • Lydon JP, DeMayo FJ, Funk CR, Mani SK, Hughes AR, Montgomery CA, Shyamala G, Conneely OM, et al. 1995 Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Gen. Develop. 9 2266–2278

    Article  CAS  Google Scholar 

  • Ong VYC and Tan BKH 2007 Novel phytoandrogens and lipidic augmenters from Eucommia ulmoides; BMC Comp. Alter. Med. 7 1–11

    Google Scholar 

  • Palace VP, Hill MF, Farahmand F and Signal PK 1999 Mobilization of antioxidant vitamin pools and hemodynamic function after myocardial infarction. Circulation 99 121–126

    Article  CAS  PubMed  Google Scholar 

  • Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF and Erdman JW 1998 Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am. J. Clin. Nutr. 68 1375–1379

    Google Scholar 

  • Rohan TE, Negassa A, Chlebowski RT, Lasser NL, McTiernan A, Schenken RS, Ginsberg M, Wassertheil-Smoller S, et al. 2008 Estrogen plus progestin and risk of benign proliferative breast disease. Cancer Epidemiol. Bioma. Prev. 17 2337–2343

  • Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, et al. 2002 Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial. J. Am. Med. Assoc. 288 321–333

    Article  CAS  Google Scholar 

  • SáFilho OG, Dias CC, Laamb GC and Vasconcelos JL 2010 Progesterone-based estrous synchronization protocols in non-suckled and suckled primiparous Bos indicus beef cows. Anim. Reprod. Sci. 119 9–16

    Article  Google Scholar 

  • Seidlova-Wuttke D, Stecher G, Kammann M, Haunschild J, Eder N, Stahnke V, Wessels J and Wuttke W 2012 Osteoprotective effects of Cimicifuga racemosa and its triterpene-saponins are responsible for reduction of bone marrow fat. Phytomedicine 19 855860

    Article  CAS  PubMed  Google Scholar 

  • Seifert-Klauss V and Prior JC 2010 Progesterone and bone: actions promoting bone health in women. J. Osteoporos. doi:10.4061/2010/845180

    PubMed Central  PubMed  Google Scholar 

  • Shuai WU, Er-wei LIU, Hong LIU, Meng WANG, Yu HAO and Xiao-yue ZHU 2010 NMR structure elucidation of triterpene saponin isolated from Dipsacus asperoides C.Y. Cheng et T. M. Ai. Chinese J. Magn. Res. 27 661–668

  • Shufelt CL and Merz CNB 2009 Contraceptive hormone use and cardiovascular disease. J. Am. Coll. Cardiol. 53 221–231

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Spitz IM and Bardin CW 1993 Clinical pharmacology of RU 486--an antiprogestin and antiglucocorticoid. Contraception 48 403–444

    Article  CAS  PubMed  Google Scholar 

  • Spitz IM 2003 Progesterone antagonists and progesterone receptor modulators: an overview. Steroid. 68 981–993

    Article  CAS  Google Scholar 

  • Stachenfeld NS 2008 Sex hormone effects on body fluid regulation. Exerc. Sport. Sci. Rev. 36 152–159

    Article  PubMed Central  PubMed  Google Scholar 

  • Stanczyk FZ 2003 All progestins are not created equal. Steroid. 68 879–890

    Article  CAS  Google Scholar 

  • Tong IL 2013 Nonpharmacological treatment of postmenopausal symptoms. Obst. Gynaecol. 15 19–25

    Article  Google Scholar 

  • Turgeon JL. McDonnell DP, Martin KA and Wise PM 2004 Hormone therapy: physiological complexity belies therapeutic simplicity. Science 304 269–273

    Article  Google Scholar 

  • Williams JK, Honore EK, Washbum SA and Clarkson TB 1994 Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomolgus monkeys. J. Am. Coll. Cardiol. 24 1757–1761

    Article  CAS  PubMed  Google Scholar 

  • Winkler UH, Schindler AE, Brinkmann US, Ebrt C and Oberhoff C 2001 Cyclic progestin therapy for the management of mastopathy and mastodynia. Gynecol. Endocrinol. 15 37–43

    PubMed  Google Scholar 

  • Wong RW, Rabie AB and Hagg EU 2007 The effect of crude extract from Radix Dipsaci on bone in micc. Phytotherapy Res. 21 596–598

  • Yaginuma T, Izumi R, Yasui H, Arai T and Kawabata M 1982 Effect of traditional herbal medicine on serum testosterone levels and its induction of regular ovulation in hyperandrogenic and oligomenorrheic women. Nihon Sanka Fujinka Gakkai Zassahi. 34 939–944

  • Yang S, Thiel KW, Geest KD and Leslie KK 2011 Endometrial cancer: reviving progesterone therapy in the molecular age. Discov. Med. 12 205–212

    PubMed  Google Scholar 

  • Yeh JY, Cheng LC, Ou BR, Whanger PD and Chang LW 2002 Differential influences of various arsenic compounds on glutathione redox status and anti-oxidative enzymes in porcine endothelial cells. Cell. Mol. Life Sci. 59 1972–1982

  • Zhang CZ, Wang SX, Zhang Y, Chen JP and Liang XM 1995 In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms. J. Ethnopharmacol. 98 295–300

    Article  Google Scholar 

Download references

Acknowledgements

This research was supported by the program of Global Research & Education on Environment and Society (GREEnS) of Tunghai University, and National Science Council research grant (NSC102-2313-B-029-004-MY3) of Taiwan, ROC.

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Correspondence to Bor-Rung Ou.

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Corresponding editor: SEYED E HASNAIN

[Ahmed HMM, Yeh J-Y, Tang Y-C, Cheng WT-K and Ou B-R 2014 Molecular screening of Chinese medicinal plants for progestogenic and anti-progestogenic activity. J. Biosci. 39 1–9] DOI 10.1007/s12038-014-9434-z

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Ahmed, H.M., Yeh, JY., Tang, YC. et al. Molecular screening of Chinese medicinal plants for progestogenic and anti-progestogenic activity. J Biosci 39, 453–461 (2014). https://doi.org/10.1007/s12038-014-9434-z

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  • DOI: https://doi.org/10.1007/s12038-014-9434-z

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