Menoprogen, a TCM Herbal Formula for Menopause, Increases Endogenous E₂in 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.

IRS2 depletion inhibits cell proliferation and decreases hormone secretion in mouse granulosa cells

“…GCs play a crucial role in female reproduction by synthesizing sex hormones, including E 2 and P 4 , as well as interacting with the oocytes [ 28 , 29 ]. Therefore, we speculate that IRS2 may participate in steroid hormone synthesis to regulate follicular growth and ovarian steroidogeneses.…”

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

“…Since 2008 we have been investigating a TCM herbal formula Menoprogen (MPG) [14,15,16,17,18,19], which has been shown to reduce menopausal symptoms and the Kupperman index in Chinese women [15]. This formula contains five medicinal and food plants, and has been used in China for centuries to treat menopausal symptoms [14,15,16,17,18,19]. In our previous work, we have shown that the mechanism of MPG is very novel in that it does not act as a phytoestrogen, but works indirectly by reducing GC apoptosis via a mechanism involving IGF-1.…”

“…Herbal medicines, including traditional Chinese medicines (TCM), are used in most countries worldwide for the management of menopausal symptoms [13,14,15,16,17,18,19]. In a pilot observational clinical trial, we have demonstrated that treatment of menopausal Chinese women with a TCM formula named Menoprogen (MPG) that contains five medicinal herbs, including Morus alba L .…”

“…In addition, treatment with this formula increased the endogenous levels of E 2 and P 4 . Furthermore, in an aged rat model of menopause, treatment with the same TCM formula, reduced ovarian granulosa cell (GC) apoptosis via a mechanism involving IGF-I, and thereby enhanced the levels of endogenous of E 2 and P 4 in these animals [14,19,20,21].…”

Multi-Dimensional Spectrum-Effect Relationship of the Impact of Chinese Herbal Formula Lichong Shengsui Yin on Ovarian Cancer

“…The dosage of administration was 2 mL/200 g, twice a day, and continuous administration for three days. Three days later, fundus blood from Wistar rats was obtained 2 h after gavage administration to obtain serum in order to investigate the effect of the prescriptions on SKOV3 tumor cell lines [ 43 , 44 ]. After incubation under 5% CO 2 at 37 °C for 24 h, SKOV3 cells (10 4 cells per well) were subsequently inoculated onto 96-well plates.…”