Pharmacokinetic Profile of Equol in the Combination of 70% Ethanolic Extract Dayak Onion Bulbs (Eleutherine bulbosa (mill.) Urb) and Cowpea (Vigna unguiculata (l.) Walp.) and their Effect on Postmenopause Syndrome

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Authors

  • Department of Pharmacology, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok ,ID
  • Department of Phytochemistry, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok ,ID
  • Department of Pharmacology, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok ,ID

DOI:

https://doi.org/10.18311/jnr/2019/24018

Keywords:

Eleutherine bulbosa, Equol, Hot Flashes, Postmenopause, Vigna unguiculata

Abstract

Alternative therapies for postmenopausal conditions are needed because of the high risks that outweigh the benefits of using hormone replacement therapy. Equol is metabolized from daidzein and is well-known as a supplement for postmenopausal conditions. Lately, liquiritigenin is also known to have a good effect on postmenopausal conditions. The aim of this study was to note the effect of the combination of Eleutherina bulbosa 70% Ethanol Extract (EEB) containing daidzein and Vigna unguiculata (EVU) containing liquiritigenin to obtain a better effect for uterine morphology, vaginal histopathology, and hot flushes. The other aim was to analyze the pharmacokinetic interaction that can affect the level of equol from EVU. Thirty-six female Sprague-Dawley rats were used in this study, 32 rats were ovariectomized (OVX) and 4 rats were Sham. Rats were divided into 9 groups: Sham group (CMC), negative group (CMC), positive group (raloxifene), EVU (100 mg/200g BW), EEB (18 mg/200g BW), The four various doses of combination EEB and EVU (D1-D4) were, EVU dosage was 100 mg/200 g BW and EEB were 36 mg, 18 mg, 9 mg, 4.5 mg/200 g BW respectively. Equol in rat serum was analyzed using HPLC/UV-V is in an isocratic condition. Observation of hot flushes was carried out every week, uterus weight wet and vaginal epithelium at the end of the treatment. The D3 and D4 combination decreased the average tail skin temperature 1.86±0.31°C and 1.83± 0.20°C respectively and the rectal temperature 0.58±0.49°C and 0.71±0.28°C (P<0.05). All groups except Sham did not increase the weight of the uterus. The D3 group increased vaginal epithelial thickness to 38.24 ± 6.47 μm (P<0.05). The combination did not significantly change equol pharmacokinetic parameters. The combination of Eleutherina bulbosa 70% ethanol extract (EEB) and Vigna unguiculata is better than EVU and EEB alone in reduced post-menopause syndrome in hypoestrogen rats without changing equol pharmacokinetic parameters.

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Published

2020-01-03

How to Cite

Lanova Hersipa, L., Katrin, ., & Bahtiar, A. (2020). Pharmacokinetic Profile of Equol in the Combination of 70% Ethanolic Extract Dayak Onion Bulbs (<i>Eleutherine bulbosa</i> (mill.) Urb) and Cowpea (<i>Vigna unguiculata</i> (l.) Walp.) and their Effect on Postmenopause Syndrome. Journal of Natural Remedies, 19(4), 188–197. https://doi.org/10.18311/jnr/2019/24018

Issue

Section

Research Articles
Received 2019-08-01
Accepted 2019-11-19
Published 2020-01-03

 

References

Singh A, Pradhan S. Menopausal symptoms of postmenopausal women in a rural community of Delhi, India: A cross-sectional study. Journal of Mid-life Health. 2014; 5(2):62. https://doi.org/10.4103/0976-7800.133989. PMid:24970983 PMCid:PMC4071646

Santoro N, Komi J. Prevalence and impact of vaginal symptoms among postmenopausal women. The Journal of Sexual Medicine. 2009; 6(8):2133–42. https://doi. org/10.1111/j.1743-6109.2009.01335.x. PMid:19493278

Stachowiak G, PertyÅ„ski T, PertyÅ„ska-Marczewska M. Metabolic disorders in menopause. Prz Menopauzalny. 2015; 14(1):59–64. https://doi.org/10.5114/pm.2015.50000. PMid:26327890 PMCid:PMC4440199

British Menopause Society. Are women suffering in silence? New BMS survey puts spotlight on significant impact of menopause British Menopause Society [internet]. 2016. Available from: https://thebms.org.uk/2016/05/ women-suffering-silence-new-bms-survey-puts-spotlightsignificant- impact-menopause/

Rey JRC, Cervino EV, Rentero ML, Crespo EC, ílvaro AO, Casillas M. Raloxifene: Mechanism of action, effects on bone tissue, and applicability in clinical traumatology practice. The Open Orthopaedics Journal. 2009; 3:14–21. https:// doi.org/10.2174/1874325000903010014. PMid:19516920 PMCid:PMC2687107

Gennari L, Merlotti D, Nuti R. Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: Focus on lasofoxifene. Clinical Interventions in Aging. 2010; 5:19–29. https://doi.org/10.2147/ CIA.S6083. PMid:20169039 PMCid:PMC2817938

Legette LL, Prasain J, King J, Arabshahi A, Barnes S, Weaver CM. Pharmacokinetics of equol, a soy isoflavone metabolite, changes with the form of equol (dietary versus intestinal production) in ovariectomized rats. Journal of Agricultural and Food Chemistry. 2014; 64:1294−1300. https://doi.org/10.1021/ jf400097m. PMid:24446705 PMCid:PMC3983397

Sa'adah NL, Anandita NW. Effect of Kt6 variant cowpea (Vigna unguiculata) extract on matrix metalloproteinase-9 and VEGF expression of corneal inflammation rat model. International Journal of PharmTech Research. 2016; 9(3):119–30.

Setchell K, Clerici C, Lephart ED, Cole SJ, Heenan C, Castellani D, et al. A potent ligand for estrogen receptor β, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. American Journal of Clinical Nutrition. 2005; 81(5):1072–1079. https:// doi.org/10.1093/ajcn/81.5.1072. PMid:15883431

Amelia T, Pratiwi D, Tjahjono DH. In silico study of the component of Eleutherine americana MERR on human estrogen receptor alpha as potential anti-breast cancer. ICCST-3. 2014; 6–9. https://doi.org/10.2991/iccst-15.2015.2

Bahtiar A, Amandasari F. The effect of 70% ethanolic extract of dayak onion bulbs and cowpea on cardiovascular parameters of hypoestrogen model rats. Journal of Natural Remedies. 2019; 19(2):74–9. https://doi.org/10.18311/ jnr/2019/23372

Bahtiar A, Dewi R. The effects of combination of dayak onion bulbs and cowpea extracts in osteoporosis. Pharmacognosy Journal. 2019; 11(4). https://doi.org/10.5530/pj.2019.11.101

Bahtiar A, Arifin S, Razalifha A, Qomariah N, Wuyung PE, Arsianti A. Polar fraction of Punica granatum L. peel extract increased osteoblast number on ovariectomized rat bone. International Journal of Health and Medicine. 2014; 2(1):65–70.

Maubach J, Bracke ME, Heyerick A, Depypere HT, Serreyn RF, Mareel MM et al. Quantitation of soy-derived phytoestrogens in human breast tissue and biological fluids by high-performance liquid chromatography. Journal of Chromatography B. 2003; 784:137–44. https://doi. org/10.1016/S1570-0232(02)00789-4

Aso T, Uchiyama S, Matsumura Y, Taguchi M, Nozaki M, Takamatsu K, et al. A natural S -equol supplement alleviates hot flushes and other menopausal symptoms in equol. Journal of Women's Health. 2012; 21(1):92–100. https://doi. org/10.1089/jwh.2011.2753. PMid:21992596

Mersereau JE, Levy N, Staub RE, Baggett S, Zogric T, Chow S, et al. Liquiritigenin is a plant-derived highly selective estrogen receptor β agonist. Molecular and Cellular Endocrinology. 2008; 283(1–2):49–57. https://doi.org/10.1016/j.mce.2007.11.020. PMid:18177995 PMCid:PMC2277338

Grady D, Sawaya GF, Johnson KC, Koltun W, Hess R, Vittinghoff E, et al. MF101, a selective estrogen receptor A modulator for the treatment of menopausal hot flushes: A phase II clinical trial. Menopause. 2009; 16(3):458–65. https:// doi.org/10.1097/gme.0b013e31818e64dd. PMid:19182698

Tagliaferri M, Creasman J, Caygill KA, Olyaie A, Leitman D, Cohen I, et al. Clinically meaningful efficacy of a nonestrogen agent: Re-analysis of phase-2 data evaluating MF101. Climacteric. 2012; 15:607–10. https://doi.org/10.3 109/13697137.2011.630113. PMid:22257013

Opas EE, Scafonas A, Nantermet PV, Wilkening RR, Birzin ET, Wilkinson H, et al. A. Control of rat tail skin temperature regulation by estrogen receptor-beta selective ligand. Maturitas. 2009; 64(1):46–51. https://doi.org/10.1016/j. maturitas.2009.07.007. PMid:19679413

Jackson RL, Greiwe JS, Schwen RJ. Emerging evidence of the health benefits of S-equol, an estrogen receptor β agonist. Nutrition Reviews. 2011; 69(8):432–48. https://doi. org/10.1111/j.1753-4887.2011.00400.x. PMid:21790611

Leitman DC, Christians U. MF101: A multi-component botanical selective estrogen receptor beta modulator for the treatment of menopausal vasomotor symptoms. Expert Opinion on Investigational Drugs. 2012; 21(7):1031–42. https:// doi.org/10.1517/13543784.2012.685652 PMid:22616988

Tabuchi M, Imamura S, Kawakami Z, Ikarashi Y, Kase Y. The blood-brain barrier permeability of 18β-glycyrrhetinic acid, a major metabolite of glycyrrhizin in Glycyrrhiza root, a constituent of the Traditional Japanese Medicine Yokukansan. Cellular and Molecular Neurobiology. 2012; 32(7):1139–46. https://doi.org/10.1007/s10571-012-9839-x. PMid:22488528

Shanafelt TD, Barton DL, Adjei AA, Loprinzi CL. Pathophysiology and treatment of hot flashes. Mayo Clinic Proceedings. 2002; 77(11):1207–18. https://doi. org/10.4065/77.11.1207. PMid:12440557

Cohen FJ, Lu Y. Characterization of hot flashes reported by healthy postmenopausal women receiving raloxifene or placebo during osteoporosis prevention trials. Maturitas. 2000; 34(1):65–73. https://doi.org/10.1016/S0378- 5122(99)00090-0

Garcia-perez. Comparative effects of estradiol, raloxifene, and genistein on the uterus of ovariectomized mice. Fertility and Sterility. 2006; 86(4):1003–5. https://doi.org/10.1016/j. fertnstert.2006.03.029. PMid:16963036

Littleton-Kearney MT, Ostrowski NL, Cox DA, Rossberg MI, Hurn PD. Selective estrogen receptor modulators: Tissue actions and potential for CNS protection. CNS Drug Reviews. 2002; 8(3):309–30. https://doi. org/10.1111/j.1527-3458.2002.tb00230.x. PMid:12353060 PMCid:PMC6741697

Pinkerton J, Thomas S. Use of SERMs for treatment in postmenopausal women Raloxifene. The Journal of Steroid Biochemistry and Molecular Biology. 2014; 142:142–54. https://doi.org/10.1016/j.jsbmb.2013.12.011. PMid:24373794

Tasci A, Bilgili H, Altunay H, Rusen M, Keskin D. Biomechanical and histological outcome of combined raloxifene - estrogen therapy on skeletal and reproductive tissues. European Journal of Pharmacology. 2010; 627(1– 3):354–61. https://doi.org/10.1016/j.ejphar.2009.11.002. PMid:19903467

Groothuis PG, Dassen HHNM, Romano A, Punyadeera C. Estrogen and the endometrium: Lessons learned from gene expression profiling in rodents and human. Human Reproduction. 2007; 13(4):405–17. https://doi.org/10.1093/ humupd/dmm009. PMid:17584823

Paterni I, Granchi C, Katzenellenbogen JA, Minutolo F. Estrogen receptors alpha (ERα) and beta (ERβ): Subtypeselective ligands and clinical potential. Steroids. 2014; 90:13–29. https://doi.org/10.1016/j.steroids.2014.06.012. PMid:24971815 PMCid:PMC4192010

Sareddy GR, Nair BC, Gonugunta VK, Zhang Q-g, Brenner A, Brann DW, et al. Therapeutic significance of estrogen receptor agonists in gliomas. Molecular Cancer Therapeutics. 2012; 11(5):1174–182. https://doi.org/10.1158/1535-7163. MCT-11-0960 PMid:22442308 PMCid:PMC3721065

Purnamasari A, Bahtiar A. Effect of dayak onion (Eleutherine bulbosa (Mill.) Urb) on uterine wall and lipid profiles of ovariectomized rat. OnLine Journal of Biological Sciences. 2018; 18(1):1–6. https://doi.org/10.3844/ojbsci.2018.1.6

Li F, Yang X, Bi J, Yang Z, Zhang C. Antiosteoporotic activity of Du-Zhong-Wan water extract in ovariectomized rats. Pharmaceutical Biology. 2016; 54(9):1857–64. https:// doi.org/10.3109/13880209.2015.1133657. PMid:26760929

Li T, Ma Y, Zhang H, Yan P, Huo L, Hu Y, et al. Differential regulation of morphology and estrogen receptor-alpha expression in the vagina of ovariectomized adult virgin rats by estrogen replacement: A histological study. International Journal of Endocrinology. 2016; 2016:1–8. https://doi.org/10.1155/2016/4740678. PMid:27990161 PMCid:PMC5136390

Bachmann GA, Nevadunsky NS. Diagnosis and treatment of atrophic vaginitis. American Family Physician. 2000; 61(10):3090–6.

Johnson SL, Farrell SA. The detection and management of vaginal atrophy. Journal of Obstetrics and Gynaecology Canada. 2004; 26(5):503–8. https://doi.org/10.1016/S1701- 2163(16)30662-4

Vermeirsch H, Broeck WVD, Simoens P. Immunolocalization of sex steroid hormone receptors in canine vaginal and vulvar tissue and their relation to sex steroid hormone concentrations. Reproduction, Fertility and Development. 2002; 14:251–8. https://doi.org/10.1071/RD01088

Khan MIH, Sohrab MH, Rony SR, Tareq FS, Hasan CM, Mazid MA. Cytotoxic and antibacterial naphthoquinones from an endophytic fungus, Cladosporium sp. Toxicology Reports. 2016; 3:861–5. https://doi.org/10.1016/j.toxrep.2016.10.005. PMid:28959613 PMCid:PMC5616083