Tanshinone IIA enhances the ovarian reserve and attenuates ovarian oxidative stress in aged mice

Background: Tanshinone IIA (TSA), a major lipophilic component extracted from the roots of Salvia miltiorrhiza Bunge, has been widely used in China for its various biological activities. However, its effect on ovarian reserve in aged mice was not studied elsewhere. Objectives: This study aimed to explore the effect of TSA on the ovarian reserve of aged mice as well as young mice. Forty weeks old mice (N = 40) were considered as aged group compared to 4 weeks old mice (N = 40), and these groups were subdivided into four subgroups (N = 10) to receive different doses of TSA (0, 10, 20, and 40 mu g/g/clay). Methods: The effect of TSA was evaluated by counting follicular number by histological examination. Basal serum levels of FSH, LH, E2, and anti-Mullerian hormone (AMH) were measured by ELISA. Moreover, the expression levels of antioxidant genes (CAT, Nrf2, GPX1), gap junction (Cx37), ERK1/2, and Smad5 family gene were examined at both mRNA (qPCR) and protein levels (western blot). Results: Follicular number, level of AMH and E2, and the expression of CAT, Nrf2, and GPX1 genes increased significantly (p <0.05) in aged mice administrated with medium (20 mu g/g/day) and high (40 mu g/g/day) doses of TSA, whereas FSH and LH levels were significantly low compared to low dose (10 mu g/g/day) and control (0 mu g/g/day) aged subgroups. However, we did not observe any effect of all doses of TSA on young mice. Conclusions: Administration of TSA with medium and high doses up-regulates the expression of antioxidative genes, reduces the oxidative injury, increases levels of AMH, and E2 levels that are relatively comparable to those in young mice, and consequently results in a healthy oocyte development.