title: 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.
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.
authors.affiliation: Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210041, China. wm96403@sina.com.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. mahady@uic.edu.
authors.forename: Gail B
authors.initials: GB
authors.lastname: Mahady
authors.affiliation: Beijing Clinical Services Center, No. 103 Chaoyang North Road, Beijing 100123, China. chuanl@msn.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210041, China. zzheng@sina.com.
authors.forename: Zhi S
authors.initials: ZS
authors.lastname: Zheng
authors.affiliation: Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210041, China. lvyenji@yahoo.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D044949:Kaempferols / Q000008:administration & dosage* / Q000737:chemistry; D008593:Menopause / Q000187:drug effects; D023421:Models, Animal; D031625:Morus / Q000737:chemistry*; D011374:Progesterone / Q000378:metabolism; D051381:Rats
chemical_list: D004967:Estrogens; D044949:Kaempferols; D011374:Progesterone; C001579:astragalin
keywords: Bax; Bcl-2; apoptosis; astragalin; herbal medicine; mechanism; menopause