Subscribe to RSS
DOI: 10.1055/s-0035-1556199
Novel mechanism of action of a traditional chinese herbal formula in an intact aged female rat model of menopause
The effects of Menoprogen (MPG), a traditional Chinese medicine formulation for menopause, were determined on granulosa cell (GC) apoptosis in an aged rat model of menopause. Intragastric administration of MPG or estradiol valerate to 14-month-old female rats for 8 weeks increased plasma estrogen levels and the weight of both ovarian and uterine tissues. Flow cytometry (FCM) analysis of the GCs from treated animals showed reductions in both the G0/G1 ratio and apoptotic peaks. Electron microscopy of the GCs showed an increase in cell size, the numbers of cytoplastic organelles and intracellular gap junctions, reappearance of secretory granules and a lack of apoptotic bodies. Data from the TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed a reduction in GC apoptosis after treatment. Immunohistochemical analysis showed a down-regulation of Bax proteins and an up-regulation of Bcl-2 proteins. In vitro, the addition of MPG medicated serum to the media of isolated GCs with cadmium chloride-induced apoptosis reduced GC apoptosis as measured by FCM analysis in the TUNEL assay. A down-regulation of caspase-3 protein in GCs treated with MPG. This work demonstrates that both MPG and estradiol valerate inhibit GC apoptosis in aged female rats, and represents a novel mechanism of action for this herbal medicine for the treatment of menopause.