Evaluation of the estrogenic properties of aqueous extracts of Tragia benthamii Baker (Euphorbiaceae) and Graptophyllum pictum (Acanthaceae) and their ability to alleviate some menopausal symptoms induced by ovariectomy in Wistar rats
Keywords:
Tragia benthamii, Graptophyllum pictum, uterotrophic effect, phytoestrogens, hot flushesAbstract
Tragia benthamii Baker (Euphorbiaceae) and Graptophyllum pictum Linn (Acanthaceae) are two Cameroonian medicinal plants traditionally used against female reproductive tract disorders, during and after the reproductive period, and as an abortifacient. Since there were no scientific data supporting the above claims and pharmacological studies characterizing their estrogenic properties, we therefore aimed to evaluate their ability to induce estrogen-like effects on primary estrogens targets, uterine, vagina and mammary gland; as well as their ability to alleviate hot flushes in ovariectomized adult rats. For this purpose, we applied a 3-day uterotrophic assay to determine the estrogenic effects of each extract and the mixture of both plants as used by traditional practitioners. The extracts were administered orally for 3 days to the 10 to 12 weeks aged ovariectomized rats. The results obtained showed that the aqueous extract of T. benthamii at the dose of 500 mg / kg BW, the aqueous extract of G. pictum at all the tested doses as well as the aqueous extract of the mixture at 275 mg / kg body weight induced a significant increase (p ˂ 0.01) of the uterine epithelium thickness. In addition, the aqueous extract of T. benthamii at the dose of 500 mg / kg BW, as well as the aqueous extract of the mixture at the doses of 50 and 275 mg / kg induced acinar development and eosinophil secretions. These results are proof of estrogen-like effects of T. benthamii and G. pictum and therefore justify the traditional use of these plants. This suggests the presence in these plants, of secondary metabolites with estrogenic properties, can induce cell proliferation, and to correct disorders of post-oophorectomy œstrogénopénia in the Wistar rats and therefore menopausal disorders.
References
. Böttner M, Christoffe l J, Jarry H, Wuttke W. Effects of long term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats. J Endocrinol 2006; 189: 77–88.
. Pinkerton JV, Stovall DW, Kighlinger RS. Advances in the treatment of menopausal symptoms. Womens Health 2009; 5: 361–84.
. Nkwo, P, Onah H. Positive attitude to menopause and improved quality of life among Igbo women in Nigeria. Int J Gynecol Obstet 2008; 103: 71–72.
. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML. Writing Group for the Women’s Health Initiative Investigators, 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 2003; 288: 321–333.
. Million Women Study Collaborators. Breast cancer and hormone replacement therapy in the Million Women Study. Lancet 2003; 362: 419–427.
. Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2005;365: 1543–1551.
. Brzezinski A, Debi A. Phytoestrogens: the “Natural” selective estrogen receptor modulators? Eur J Obstet Gynecol Reprod Biol 1999;85:47–51.
. Pitkin, J., 2012. Alternative and complementary therapies for menopause. Menopause Int 2012; 18: 20–27.
. Kaufert P, Boggs B, Ettinger NF, Woods WH. Women and menopause: beliefs, attitudes and behaviors. The North American Menopause Society 1997 Menopause Survey, Menopause 1998; 5: 197–202.
. Ferrari A. Soy extract phytoestrogens with high dose of isoflavones for menopausal symptoms. J Obstet Gynaecol Res 2009 ;35: 1083–90.
. Bouquet A, Debray. Féticheurs et plantes médicinales de la Cote d’Ivoire. Office de la Recherche Scientifique et Technique d’Outre-mer (ORSTOM), Paris 1974 ; pp. 71.
. Jiofack T, Fokunang C, Guedje N, Kemeuze V, Fongnzossie E, Nkongmeneck BA, Mapongmetsem PM, Tsabang N. Ethnobotanical uses of medicinal plants of two ethnoecological regions of Cameroon. Intl J of Med and Medical Sciences 2010;2(3) pp. 60-79.
. Perry LM. Medicinal plants of East and South-East Asia; Attributed Properties and Uses MIT press, Cambridge, United States and London 1980;p. 2.
. Ozaki Y, Sekita S, Soedigdo S, Harada M. (1989), Anti-inflammatory effect of Graptophyllum pictum (L.) GRIFF. Chemical pharmaceutical bulletin 1989;37(10): 2799-802.
. Stella OOD, Grace EU, Herbert ABC, Samuel AA. Oxytocic and anti-implantationactivities of the leaf extracts of Graptophyllum pictum (Linn.) Griff. (Acanthaceae). AfricanJournal of Biotechnology 2009; 8(21):5979-84.
. Olagbende-Dada SO, Ogbonnia SO, Coker HAB, Ukpo GE. Blood glucose lowering effect of aqueous extract of Graptophyllum pictum (Linn) Griff. On alloxan-induced diabetic rats and its acute toxicity in mice. African Journal of Biotechnology 2011;10(6) 1039-1043.
. Lane NE,Yao W,Kinney JH,Modin G, Balooch M, Wronski TJ,2003.Both hPTH (1-34)and bFGF increase trabecular bone mass in osteopenic rats but they have different effects on trabecular bone architecture. J Bone Miner Res. 2003; 18: 2105–2115.
. Zingue S, Njamen D, Tchoumtchoua J, Halabalaki, M, Simpson, E, Clyne C, Magne Nde CB.Effectsof Millettia macrophylla (Fabaceae) extracts on Estrogen target organs of female Wistar rat. J Pharmacol Sci 2013; 123: 120–131.
. Berendsen HHG, Weekers AHJ, Kloosterboer HJ.Effect of tibolone and Raloxifene on the tail temperature of estrogen-deficient rats. Eur J Pharmacol 2001; 419:47–54.
. Njamen D, Djiogue S, Zingue S, Mvondo MA, Nkeh-Chungag BN 2013. In vivo and in vitro estrogenic activity of extracts from Erythrina poeppigiana (Fabaceae). J Complement Integr Med 2013; 10:1–11.
. Nkeh-Chungag BN, Tiya S, Mbafor JT, Ndebia EJ, Rusike S, Iputo JE. Effects of the methanol extractof Erythrina abyssinica on hot flashes in ovariectomized rats. Afr J Biotechnol 2013; 12: 598–601.
. Maswood, Cosmi S, Alfinito PD, Leventhal L, Deecher DC. The role of the selective serotonin reuptake inhibitor fluoxetine in temperature regulation in ovariectomized rat models. Neuroendocrinology 2006; 84: 330–338.
. O’Brien JE, Peterson TJ, Tong MH, Lee EJ, Pfaff LE, Hewitt SC, Korach KS, Weiss J Jameson JL. Estrogen-induced prolifération of uterine epithelial cells is independent of estrogen receptor α binding to classical estrogen response elements. J Biol Chem 2006; 281: 26683–26692.
. Westwood FR. The female rat reproductive cycle: a practical histological guide to staging. Toxicol Pathol. 2008;3(6):375–84.
. Hewitt SC, Deroo BJ, Hansen K, Collins J, Grissom S, Afshari CA, Korach KS. Estrogen receptor-dependent genomic responses in the uterus mirror the biphasic physiological response to estrogen. Mol Endocrinol 2003;17:2070–83.
. Rang HP, Dale MM, Ritter JM, Moore P. K. Pharmacology. Churchill Livingstone, Elsevier science limited, 2003; 11-20.
. Couse JF, Korach KS. Contrasting phenotypes in reproductive tissues of female estrogen receptor null mice. Ann NY Acad Sci. 2001; 948: 1-8.
. Weihua Z, Andersson S, Cheng G, Simpson ER, Warner M, Gustafsson JA. Update on estrogen signalling. FEBS Lett 2003; 546: 17–24.
. Buchanan DL, Kurita T, Taylor JA, Lubahn DB, Cunha GR, Cooke PS. Role of stromal and epithelial estrogen receptors in vaginal epithelial proliferation, stratification, and cornification. Endocrinology. 1998;139:4345–52.
. Buchanan DL, Setiawan T, Lubahn DB, Taylor JA, Kurita T, Cunha GR, Cooke PS. Tissue compartment-specific estrogen receptor-a participation in the mouse uterine epithelial secretory response. Endocrinology 1999;140:484–91.
. Couse JF, Curtis SW, Washburn TF, Lindzey J, Golding TS, Lubahn DB, Smithies O, Korach KS. Analysis of transcription and estrogen insensitivity in the female mouse after target disruption of the estrogen receptor gene. Mol Endocrinol. 1995;9:1441–54.
. Dahlman-Wright K, Cavailles V, Fuqua SA, Jordan VC, Katzenellenbogen JA, Korach KS,Maggi A, Muramatsu M, Parker MG, Gustafsson JA. International Union of Pharmacology. LXIV. Estrogen receptors. Pharmacol Rev 2006; 58: 773–781.
. Pelletier G, Labrie C, Labrie F. Localization of oestrogen receptor alpha, oestrogen receptor beta and androgen receptors in the rat reproductive organs. J Endocrinol 2000;165: 359–70
. Wang H, Eriksson H, Sahlin L. Estrogen receptors alpha and beta in the female reproductive tract of the rat during the estrous cycle. Biol Reprod. 2000; 63: 1331–40
. Santell RC, Chang YC, Nair MG Helferich WG. Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic / pituitary axis in rats. J Nutr 1997;127: 263–269.
. Koang MP. Traitement des bouffées de chaleur par acupuncture. Meridien 1992 95: 121–140.
. Santoro N, 2008.Symptoms of menopause:hot flushes. Clin Obstet Gynecol 2008; 51:539–548.
. Crisafulli A, Marini H, Bitto A , Altavilla D, Squadrito G, Romeo A, Adamo EB, Marini R, D’Anna R, Corrado F, Bartolone S, Frisina N, Squadrito F. Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT-and placebo-controlled study. Menopause 2004; 11: 400–404.
. D’Anna R, Cannata ML, Marini H, Atteritano M, Cancellieri F, Corrado F, et al.,Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epitheliumin post-menopausal women: a 2-year randomized, double-blind, placebo-controlled study, Menopause 2009; 16 301–306.
. Erlik Y, Meldrum DR, Judd H. Estrogen levels in post menopausal women with hot flashes, Obstet Gynecol. 1982; 59:403–407.
. Freedman RR, Blacker CM. Estrogen raises the weating threshold in postmenopausal women with hot flashes. Fertil Steril 2002; 77: 487–490.
. Dacks PA, Rance NE. Effects of estradiol on the thermoneutral zone and core temperature in ovariectomized rats, Endocrinology. 2010; 51: 1187–1193.
. Freedman RR. Physiology of hot flashes. Am. J. Hum. Biol.2001;13,4553–4564.
. Le Bail JC, Champavier Y, Chulia AJ, Habrioux G. Effects of phytoestrogens on aromatase, 3beta and 17beta-hydroxysteroid dehydrogenase activities and human breast cancer cells. Life Sci 2000; 66: 1281–1291.
