Abstract
Objective
To investigate the phytoestrogenic effects of Schizandra chinensis (SC) extract by regulating the activation of estrogen receptor.
Methods
Western blotting assay was performed to investigate the effect of SC extract (1, 10, 100 μg/mL) on the expression of estrogen receptor (ER)-α and -β in MCF-7 human breast cancer cells. Cell viability and the levels of c-fos and c-Jun were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blot analysis, respectively, to further confirm the anti-cancer effect of SC extract.
Results
SC extract increased the expressions of ER-α and -β (P<0.001), whereas cell viability and the expressions of growth factors (c-fos and c-Jun) were inhibited (P< and <0.001, respectively) following treatment.
Conclusions
SC extract has phytoestrogenic effects, and its biological action includes ER binding ability with low cancer risk. Therefore, SC might be a potential source for the development of a new alternative to hormone therapy in menopause.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Gustafsson JA. What pharmacologists can learn from recent advances in estrogen signalling. Trends Pharmacol Sci 2003;24:479–485.
Winuthayanon W, Piyachaturawat P, Suksamrarn A, Ponglikitmongkol M, Arao Y, Hewitt SC, et al. Diarylheptanoid phytoestrogens isolated from the medicinal plant Curcuma comosa: biologic actions in vitro and in vivo indicate estrogen receptor-dependent mechanisms. Environ Health Perspect 2009;117:1155–1161.
Tiyasatkulkovit W, Charoenphandhu N, Wongdee K, Thongbunchoo J, Krishnamra N, Malaivijitnond S. Upregulation of osteoblastic differentiation marker mRNA expression in osteoblast-like UMR106 cells by puerarin and phytoestrogens from Pueraria mirifica. Phytomedicine 2012;19:1147–1155.
Tham DM, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab 1998;83:2223–2235.
Knight DC, Eden JA. A review of the clinical effects of phytoestrogens. Obstet Gynecol 1996;87:897–904.
Black LJ, Sato M, Rowley ER, Magee DE, Bekele A, Williams DC, et al. Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J Clin Invest 1994;93:63–69.
Innocenti G, Vegeto E, Dall’Acqua S, Ciana P, Giorgetti M, Agradi E, et al. In vitro estrogenic activity of Achillea millefolium L. Phytomedicine 2007;14:147–152.
Sylvestre M, Pichette A, Longtin A, Nagau F, Legault J. Essential oil analysis and anticancer activity of leaf essential oil of Croton flavens L. from Guadeloupe. J Ethnopharmacol 2006;103:99–102.
Caichompoo W, Zhang QY, Hou TT, Gao HJ, Qin LP, Zhou XJ. Optimization of extraction and purification of active fractions from Schisandra chinensis (Turcz.) and its osteoblastic proliferation stimulating activity. Phytother Res 2009;23:289–292.
Szopa A, Ekiert H. Production of deoxyschizandrin and gamma-schizandrin in shoot-differentiating and undifferentiating callus cultures of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine). J Biotechnol 2013;165:209–213.
Miller CP, Collini MD, Harris HA. Constrained phytoestrogens and analogues as ERbeta selective ligands. Bioorg Med Chem Lett 2003;13:2399–2403.
Waters KM, Rickard DJ, Riggs BL, Khosla S, Katzenellenbogen JA, Katzenellenbogen BS, et al. Estrogen regulation of human osteoblast function is determined by the stage of differentiation and the estrogen receptor isoform. J Cell Biochem 2001;83:448–462.
Wu X, Subramaniam M, Grygo SB, Sun Z, Negron V, Lingle WL, et al. Estrogen receptor-beta sensitizes breast cancer cells to the anti-estrogenic actions of endoxifen. Breast Cancer Res 2011;13:R27.
Huang Y, Ray S, Reed JC, Ibrado AM, Tang C, Nawabi A, et al. Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells. Breast Cancer Res Treat 1997;42:73–81.
Perillo B, Sasso A, Abbondanza C, Palumbo G. 17betaestradiol inhibits apoptosis in MCF-7 cells, inducing bcl-2 expression via two estrogen-responsive elements present in the coding sequence. Mol Cell Biol 2000;20:2890–2901.
Ahamed S, Foster JS, Bukovsky A, Wimalasena J. Signal transduction through the Ras/Erk pathway is essential for the mycoestrogen zearalenone-induced cell-cycle progression in MCF-7 cells. Mol Carcinog 2001;30:88–98.
Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, et al. Estrogen receptors: how do they signal and what are their targets. Physiol Rev 2007;87:905–931.
Dall’Acqua S, Tome F, Vitalini S, Agradi E, Innocenti G. In vitro estrogenic activity of Asplenium trichomanes L. extracts and isolated compounds. J Ethnopharmacol 2009;122:424–429.
Muller R. Cellular and viral fos genes: structure, regulation of expression and biological properties of their encoded products. Biochim Biophys Acta 1986;823:207–225.
Cohen DR, Curran T. The structure and function of the fos proto-oncogene. Crit Rev Oncog 1989;1:65–88.
Curran T, Franza BR, Jr. Fos and Jun: the AP-1 connection. Cell 1988;55:395–397.
Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, et al. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 1995;270:1491–1494.
Coutts AS, Murphy LC. Elevated mitogen-activated protein kinase activity in estrogen-nonresponsive human breast cancer cells. Cancer Res 1998;58:4071–4074.
Shim WS, Conaway M, Masamura S, Yue W, Wang JP, Kmar R, et al. Estradiol hypersensitivity and mitogenactivated protein kinase expression in long-term estrogen deprived human breast cancer cells in vivo. Endocrinology 2000;141:396–405.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by High Value-added Food Technology Development Program (111007-3), Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Kim, M.H., Lee, Hs., Hong, S.B. et al. Schizandra chinensis exhibits phytoestrogenic effects by regulating the activation of estrogen receptor-α and -β. Chin. J. Integr. Med. (2017). https://doi.org/10.1007/s11655-017-2966-y
Received:
Published:
DOI: https://doi.org/10.1007/s11655-017-2966-y