Yu Yang's research team from the Department of Obstetrics and Gynecology of Peking University Third Hospital published the research results of the mechanism of ginsenoside Rb1 protection against oxidative stress-induced ovarian granule cell damage in Science China-Life Sciences

In November 2022, Yu Yang's research team from the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, was published in Science China-Life Sciences, an authoritative journal in the field of international biology Science in China: Life Sciences) was published in a research article entitled "Ginsenoside Rb1 Inhibits Oxidative Stress-Induced Ovarian Granulosa Cell Injury through Akt-FoxO1 Interaction" (Ginsenoside Rb1 inhibits oxidative stress-induced ovarian granule cell damage by activating Akt-FoxO1 interaction).

Female infertility and spontaneous abortion have become research hotspots in the field of reproductive medicine and clinical problems
that need to be solved urgently.
Granulosa Cells (GCs), a key component of follicles, provide the microenvironment
for oocyte growth, development, and maturation.
The research group showed that the peroxidative stress of GCs induced by advanced age is one of the core factors in the decline of
female fertility.
Traditional Chinese medicine is a treasure of traditional medicine in China, among which ginsenoside Rb1 has a strong antioxidant effect, but whether it can inhibit oxidative damage of ovarian granule cells in elderly women, improve ovarian function and improve female fertility is still lacking in systematic research
.

Firstly, ovarian granule cells and 50 women of childbearing age (≥ 38 years old) and 50 women of childbearing age (≥ 38 years old) were obtained from 50 young women of childbearing age (age less than or equal to 30 years old), and it was clear that there were significant differences in phenotypes such as oxidative stress and apoptosis between the two groups of granulocytes, and the addition of ginsenoside RB1 could effectively reduce the level of oxidative stress, reduce the LDH and MDA of hGL cells in women in the elderly group, restore mitochondrial membrane potential, and reverse the excessive accumulation of ROS.
Inhibits apoptosis
.

Furthermore, using young and aged ICR mouse models to give or not give Rb1 for 2 weeks, explore whether Rb1 has a protective effect of fertility in vivo, and determine that Rb1 prolongs the fertility cycle of elderly mice through immunofluorescence, Western blotting, immunoprecipitation, siRNA silencing and small molecule inhibitors, and this effect mainly plays a role by regulating the Akt-FoxO1 signaling pathway
。

In-depth analysis of its molecular mechanism shows that Rb1 protects AKT activation caused by peroxide damage by increasing the phosphorylation of the Ser473 site of AKT protein
.
Rb1 also promotes the binding of p-Akt to FoxO1 and promotes phosphorylation
of FoxO1.
Akt siRNA silencing, the Akt inhibitor LY294002, and the FoxO1 inhibitor AS1842856 can all attenuate the biological effects
of Rb1.

Therefore, it is proved that ginsenoside Rb1 inhibits age-related oxidative damage of granule cells by activating Akt phosphorylation at the Ser473 site to interact with FoxO1, and the results provide theoretical support for further exploration of the potential of granule cells to regulate oocyte development, and provide potential new strategies
for clinical improvement of ovarian function in elderly women.

Ginsenoside Rb1 interacts with FoxO1 by activating phosphorylation at the Akt Ser473 site, thereby inhibiting the molecular pathway of oxidative damage in granule cells

Science China-Life Sciences, co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China, was selected as a key journal of the Excellence Action Plan for Chinese Science and Technology Journals and ranked TOP5% in the international JCR field of biology
.

Dr.
Zhou Ping of the Department of Obstetrics and Gynecology is the first author of the paper, and researcher Yu Yang is the corresponding author
.
This paper was supported
by the National Natural Science Foundation of China, the National Key Research and Development Program of China and other projects.

Full text link:

　　https://link.
springer.
com/article/10.
1007/s11427-021-2080-x

(Peking University Third Hospital)