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Molecules 2016, 21(5), 675; doi:10.3390/molecules21050675

Astragalin, a Flavonoid from Morus alba (Mulberry) Increases Endogenous Estrogen and Progesterone by Inhibiting Ovarian Granulosa Cell Apoptosis in an Aged Rat Model of Menopause

1,†
,
2,†
,
3,* , 1
and
1
1
Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210041, China
2
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
3
Beijing Clinical Services Center, No. 103 Chaoyang North Road, Beijing 100123, China
These authors have contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 16 February 2016 / Revised: 5 May 2016 / Accepted: 10 May 2016 / Published: 21 May 2016
(This article belongs to the Section Natural Products)
View Full-Text   |   Download PDF [2354 KB, uploaded 21 May 2016]   |  

Abstract

Background: To determine the mechanism by which the flavonoid glycoside astragalin (AST) reduces ovarian failure in an aged rat model of menopause. Methods: The in vivo effect of AST on granulosa cell (GC) apoptosis in aged female rats was determined using flow cytometry. In vitro, the effects of AST on cultured GCs were investigated using the MTT proliferation assay and western blot assays. Results: Aged rats had significantly higher GC apoptosis as compared with young female rats. Treatment of aged rats with AST (all three doses; p < 0.01) or Progynova (p < 0.01) significantly reduced GC apoptosis as compared with the aged controls. The proportions of total apoptotic GCs was 25.70%, 86.65%, 47.04%, 27.02%, 42.09% and 56.42% in the normal, aged, 17β-estradiol (E2), high dose AST, medium dose AST, and low dose AST-treated groups, respectively. Significant increases of serum E2 and P4 levels, as well as altered levels of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. In cultured rat GCs, AST stimulated GC proliferation, E2 and progesterone (P4) secretion, reduced apoptosis, reduced the level of the pro-apoptotic protein Bcl-2 (p < 0.01), but had no effect on BAX. Conclusions: AST enhanced ovarian function in aged female rats by increasing E2 and P4 levels, and reducing ovarian GC apoptosis via a mechanism involving Bcl-2. These data demonstrate a new pharmacological activity for AST, as well as a novel mechanism of action, and further suggest that AST may be a new therapeutic agent for the management of menopausal symptoms. View Full-Text
Keywords: astragalin; apoptosis; Bax; Bcl-2; herbal medicine; mechanism; menopause astragalin; apoptosis; Bax; Bcl-2; herbal medicine; mechanism; menopause
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MDPI and ACS Style

Wei, M.; Mahady, G.B.; Liu, D.; Zheng, Z.S.; Lu, Y. Astragalin, a Flavonoid from Morus alba (Mulberry) Increases Endogenous Estrogen and Progesterone by Inhibiting Ovarian Granulosa Cell Apoptosis in an Aged Rat Model of Menopause. Molecules 2016, 21, 675.

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