Effect of Rhei Radix Et Rhizome on treatment of polycystic ovary syndrome by regulating PI3K/AKT pathway and targeting EGFR/ALB in rats.

Abstract

Abnormal endocrine metabolism caused by polycystic ovary syndrome (PCOS) poses a serious risk to reproductive health in females. According to Traditional Chinese Medicine (TCM) theories, the leading causes of PCOS include turbid phlegm, blood stasis and stagnation of liver Qi. Rhei Radix Et Rhizome is widely used in TCM to attack stagnation, clear damp heat, relieve fire. Rhei Radix Et Rhizome is an important part of the TCM formulas for the treatment of PCOS, which has a long history of medicinal use. However, the specific effect and mechanisms of Rhei Radix Et Rhizome on PCOS have yet to be elucidated. The object of this study aimed to investigate the effect and its pharmacological mechanism of Rhei Radix Et Rhizome on the treatment of polycystic ovary syndrome. PCOS was induced in female Sprague Dawley (SD) rats by administering letrozole (1 mg/kg, per orally, p.o.) for 21 days, then treated with Rhei Radix Et Rhizome at doses of 0.6g/kg or 1.2g/kg. Rats weight, blood glucose and estrus period are measured, and serum hormone include free testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and ovarian lesions were observed to determine the effects of Rhei Radix Et Rhizome. Network pharmacology and molecular docking predicted the targets of Rhei Radix Et Rhizome on PCOS. Epidermal growth factor receptor (EGFR), albumin (ALB), PI3K and P-AKT/AKT protein expression levels in ovarian tissues were assessed by Western blot. Rhei Radix Et Rhizome reduce abnormal weight and fasting blood glucose induced by letrozole (n=5, p < 0.01), and improve the disturbed estrus cycle, reduce T, LH levels and LH/FSH ratio of PCOS rats (n=4, p < 0.01). In addition, it alleviates the polycystic changes of ovaries in PCOS rats and reduces ovarian histopathological damage (n=4, p < 0.01). Additionally, the core active components of Rhei Radix Et Rhizome for PCOS include Sennoside D_qt, Procyanidin B-5,3'-O-gallate, and Mutatochrome, which strongly bind to core therapeutic targets ALB and EGFR. Furthermore, the treatment reduces the increase of EGFR and ALB induced by letrozole (n=4, p < 0.01). KEGG pathway enrichment analysis highlights endocrine resistance and prolactin signaling pathway, in both of which the PI3K/AKT pathway plays a crucial role. Our results show Rhei Radix Et Rhizome rescue the abnormal expression of PI3K/AKT pathway in PCOS rats (n=4, p < 0.01). However, no significant dose-dependent relationship was observed in the tested dose range for the above experiments. These findings suggest that Rhei Radix Et Rhizome can regulate the PI3K/AKT pathway and target EGFR and ALB to treat polycystic ovary syndrome in rats. This study provides a scientific basis for the use of Rhei Radix Et Rhizome in the treatment of PCOS and highlights its potential mechanism through modulation of the PI3K/AKT pathway.