Network pharmacology and experimental validation to elucidate the mechanism of the treatment of polycystic ovary syndrome with insulin resistance by Resina Draconis.

Background: Resina Draconis(RD) is a traditional Chinese medicine that activates blood circulation and removes blood stasis. Modern pharmacological studies have proved that RD has hypoglycaemic, pancreatic islets-protective, oestrogenic activity, anti-inflammatory, antibacterial and anti-tumour effects. Studies have shown that insulin resistance (IR) is the core pathological mechanism of polycystic ovary syndrome (PCOS), and RD can lower blood glucose to ameliorate IR, which has achieved significant results in the treatment of diabetes. However, the mechanism of action of RD in the treatment of PCOS-IR is still unclear.

Methods: Network pharmacology analysis was used to predict the potential therapeutic targets of the active ingredients of RD. Experimental validation used a rat model of insulin resistance in PCOS; PCOS-IR symptoms were assessed, ovarian pathology was evaluated, and serum levels of insulin and sex hormones were determined. Expression levels of the PI3K, p-PI3K, Akt, p-Akt, GLUT4, FOXO3a, and P27 proteins were also measured in rat ovaries, along with mRNA expression levels of PI3K, Akt, GLUT4, FOXO3a, and P27.

Results: Network pharmacological analyses indicated that the PI3K/Akt signalling pathway may play an important role in the treatment of PCOS-IR rats with RD. Experiments in PCOS-IR rats showed that RD significantly reversed insulin resistance, improved pathological changes in the ovaries, increased serum levels of follicle stimulating hormone (FSH) and estradiol (E2), and decreased levels of luteinizing hormone (LH), testosterone (T) and insulin. In addition, RD increased the levels of PI3K, p-PI3K, Akt, p-Akt and GLUT4, and decreased the levels of FOXO3a and P27 in the ovarian tissues of PCOS-IR rats, suggesting that RD may improve the symptoms of PCOS-IR in rats through the PI3K/Akt signalling pathway.

Conclusions: RD might improve insulin resistance and ovarian function in PCOS-IR by upregulating PI3K, p-PI3K, Akt, p-Akt and GLUT4 expression and downregulating FOXO3a and P27, thereby activating the PI3K/Akt signaling pathway. RD also regulated the LH/FSH ratio, increased E2 levels, reduced LH and T levels, and alleviated PCOS-IR symptoms in a rat PCOS-IR model.