title: Menoprogen, a TCM Herbal Formula for Menopause, Increases Endogenous E2 in an Aged Rat Model of Menopause by Reducing Ovarian Granulosa Cell Apoptosis.
abstract: The effect of Menoprogen (MPG) on ovarian granulosa cell (GC) apoptosis was investigated in vitro and in vivo in an aged rat model of menopause. Intragastric administration of Menoprogen or estradiol valerate to 14-month-old senile female rats for eight weeks increased plasma E2 levels, as well as the weight of both ovarian and uterine tissues. Flow cytometric (FCM) analysis of isolated GCs from MPG-treated aged rats showed reductions in the G0/G1 ratio and apoptotic peaks. Isolated GCs also exhibited an increase in cell size and the number of cytoplastic organelles and intracellular gap junctions, the reappearance of secretory granules, and a lack of apoptotic bodies as determined by TEM. Results from a TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed a reduction in TUNEL-positive GCs after MPG treatment. Immunohistochemical analysis showed a downregulation of proapoptotic Bax proteins and an upregulation of antiapoptotic Bcl-2 proteins. The addition of MPG-medicated serum to the media of cultured GCs also reduced cadmium chloride-induced apoptosis and downregulated caspase-3 protein expression. This work demonstrates that Menoprogen inhibits GC apoptosis in aged female rats and thereby increases E2 production. This represents a novel mechanism of action for this herbal medicine in the treatment of menopausal symptoms.
authors.affiliation: Traditional Chinese Medicine Department, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Traditional Chinese Medicine Department, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.affiliation: Institute of Botany, Chinese Academy of Science, Nanjing, Jiangsu 210014, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Hainan Medical College, Haikou, Hainan 571101, China.
authors.forename: B J
authors.initials: BJ
authors.lastname: Tan
authors.affiliation: Traditional Chinese Medicine Department, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Temitope O
authors.initials: TO
authors.lastname: Lawal
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Gail B
authors.initials: GB
authors.lastname: Mahady
authors.affiliation: Beijing Clinical Services Center, No. 103 Chaoyang North Road, Beijing 100123, China.
authors.forename: Daniel
authors.initials: D
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008593:Menopause / Q000187:drug effects*; D006080:Ovarian Follicle / Q000187:drug effects* / Q000473:pathology; D051381:Rats
chemical_list: D004365:Drugs, Chinese Herbal; C529990:menoprogen