image: (A) The chemical structure of ginsenoside Rb1. (B) Identification of hGL cells with FSHR. (C) The ROS levels expressed in hGL cells was detected by flow cytometry. (D) Quantitative analysis of the mean ROS fluorescence intensity. (E) Effects of Rb1 on LDH leakage. (F) The levels of MDA as measured by related assay kits. (G) Apoptosis-related protein levels in hGL cells as assessed by western blot. (H) The densitometric analysis of cleaved caspase-3 expression. (I) The densitometric analysis of cleaved caspase-9 expression. Data are expressed as the mean ± SEM from three independent experiments. # P < 0.05, ## P < 0.01 vs. young; *P < 0.05, **P < 0.01 vs. old group. Ginsenoside Rb1 alleviates GCs damage in aged women. view more
Credit: ©Science China Press
This study is led by Prof. Yang Yu (Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital). Age-related female infertility and increase of the probability of spontaneous abortion has become the focus in the field of reproductive medicine in recent years. Integrative therapy plays a critical role in the therapy of aging-related diseases, of which Traditional Chinese medicine has been used extensively in the prevention and treatment of chronic conditions, especially those related to oxidative damage. And with a solid research foundation in the pharmacological effects of Ginsenoside Rb1, Dr. Zhou Ping, the first author of this study, was excited to further verify its ability and mechanism in the rescue of the aged ovaries.
As the key components of a follicle, GCs form the microenvironment for oocyte development, maturation, and function. The process of oxidative stress in GCs, resulted in follicular atresia and even ovarian dysfunction. Ovarian granulosa cells were obtained from 50 young women (≤30 y.o.) and 50 aged women (≥38 y.o.) by the team at the IVF center of Peking University Third Hospital. The researchers also used young and aged ICR mice administered with or without Rb1 (10 mg/kg, i.p.) for 2 weeks for the animal experiments.
The team found that Rb1 effectively decreased LDH and MDA, and reversed the apoptotic-related protein levels in GCs from old patients. Similar results were found in mice. And they sought to further determine the underlying mechanism focusing on a previously reported Akt signaling pathway.
Related experiments were carried out in the Key Laboratory of Assisted Reproduction (Peking University). Results showed that the mitochondrial membrane potential was restored and the overaccumulation of ROS was reversed by Rb1. Rb1 preserved peroxide-impaired Akt activation, to some extent, by increasing phosphorylation at Ser 473. Rb1 also facilitated p-Akt binding to FoxO1 and promoted the phosphorylation of FoxO1. SiRNA silencing of Akt, Akt inhibitor LY294002, and FoxO1 inhibitor AS1842856 attenuated the effects of Rb1.
This work not only determined a formerly unrecognized role for ginsenosides in the protection of granulosa cells from oxidative damage, but also clarified that pharmacological regulation of Akt/FoxO1 might be effective in treating ageing-related ovarian dysfunction.
See the article:
Ginsenoside Rb1 Inhibits Oxidative Stress-Induced Ovarian Granulosa Cell Injury through Akt-FoxO1 Interaction
https://www.sciengine.com/doi/10.1007/s11427-021-2080-x
Journal
Science China Life Sciences