Abstract
Background: Berberine (Ber), a Chinese herbal monomer has been reported to exhibit an array of pharmacological activities relating to the lowering of blood glucose and the treatment of polycystic ovarian syndrome (PCOS). However, the related mechanism underlying these activites is not clear. In the current study, we aimed to elucidate the effect of Ber on rat model of PCOS by PI3K/AKT signaling pathway.Methods: A letrozole-induced rat PCOS model and primary ovarian granulosa cells model to explore the protective effect and the mechanism of action of Ber. In PCOS rats, the values of fasting blood glucose (FBG) insulin resistance (HOMA-IR), fasting insulin (FINS) values and the serum hormone levels were measured. The ovarian tissues were stained with HE and TUNEL to undergo pathological and apoptosis examination. Moreover, the effect of Ber on proliferation and apoptosis of granulosa cells was detected by CCK-8 and flow cytometry. And then the influence of Ber on granulosa cells was confirmed by blockade of the PI3K/AKT pathway. In addition, the modulatory effect on the expression of related proteins by blockade of PI3K/AKT was demonstrated via western blot.Results: We found that Ber was able to recover the serum hormone levels and improve insulin resistance (IR) in PCOS rat model. The morphological lesion and apoptosis of the ovary was also restored with the Ber treatment. Blockade of the PI3K/AKT pathway attenuated the influences of Ber on proliferation and apoptosis of granulosa cells. Due to this, we discovered a correlation between the PI3K/AKT signaling pathway and the beneficial effects of Ber, demonstrating that its application could alter the expression levels of key proteins in the PI3K/APT pathway.Conclusion: The beneficial effects of Ber on PCOS, including alter serum hormone levels, recover ovary morphological lesions, improve IR, improve cell viability and inhibition of apoptosis, which is mediated through the PI3K/AKT pathway.