[Mechanism of Bushen Culuan Decoction in regulating SIRT1 signaling pathway to improve mitochondrial function and...

Premature ovarian failure(POF) has been a global public health concern with a rising incidence, severely affecting women's reproductive health and quality of life. This study aims to investigate the mechanisms by which Bushen Culuan Decoction(BCD) ameliorates ovarian mitochondrial dysfunction to improve POF. Fifty female BALB/c mice were randomly divided into control group, model group, positive drug group, low-, and high-dose BCD group. POF mouse model was established by subcutaneous injection of D-gal. Body weight and gonadal indices were observed, and changes in the estrous cycle were monitored. The level of FSH, E_2, and LH in serum was measured using ELISA. Ovarian tissue morphology and follicle counts were assessed via HE staining. In vitro model of human ovarian granulosa cells(KGN) injury was established to quantify mitochondrial number and ROS level. Protein expression of SIRT1 and PGC-1α was analyzed using Western blot. The results showed that compared with control group, model group reduced body weight gain, disordered estrous cycles, decreased ovarian and uterine indices, elevated serum FSH and LH levels, reduced E_2 level, decreased number of follicles at all developmental stages, and increased number of atretic follicles. Compared with model group, BCD group increased in ovarian and uterine indices, decreased in serum FSH and LH levels, increased in E_2 level, and decreased number of atretic follicles in mice. In vitro, BCD increased mitochondrial number, reduced ROS production, and upregulated SIRT1 and PGC-1α expressions in KGN. In conclusion, BCD improves the estrous cycle, increases ovarian and uterine indices, lowers serum FSH and LH levels, elevates E_2 level, reduces the number of atretic follicles, and protects ovarian function in POF mice. These effects may be associated with activation of the SIRT1 signaling pathway, thereby improving mitochondrial function and reducing oxidative stress in KGN.