Ginsenoside Rb1 inhibits oxidative stress-induced ovarian granulosa cell injury through Akt-FoxO1 interaction.

ABSTRACT

Ginsenoside Rb1 shows a strong antioxidant effect and has potential activation effects on Akt. The aim of the present study was to investigate the protective effect of Rb1 on age-related ovarian granulosa cell injury. Ovarian granulosa cells (GCs) were obtained from 50 young women (≤30 years) and 50 aged women (≥38 years) at an IVF center. Young and aged ICR mice were administered with or without Rb1 (10 mg kg-1, i.p.) for 2 weeks. The protective effects of Rb1 were investigated and the role of Rb1 on the modulation of Akt-FoxO1 interaction was determined with immunofluorescence, Western blotting, immunoprecipitation, siRNA silencing and pharmacological inhibitor. Rb1 effectively decreased LDH and MDA, and reversed the apoptotic-related protein levels in hGL cells from old patients. Similar results were found in mice. In addition, 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 Ser473. 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. Ginsenoside Rb1 inhibits age-related GCs oxidative damage by activating Akt phosphorylation at Ser473 and by further interaction with FoxO1.