Curcumin Inhibits Hyperandrogen-Induced IRE1α-XBP1 Pathway Activation by Activating the PI3K/AKT Signaling in Ovarian Granulosa Cells of PCOS Model Rats

Hyperandrogenism is a common characteristic of polycystic ovary syndrome (PCOS). Long-term, continuous exposure to hyperandrogenic environments may cause excessive endoplasmic reticulum (ER) stress in ovarian granulosa cells (GCs). Curcumin is a polyphenol extracted from turmeric rhizomes which has several pharmacological effects that may benefit patients with PCOS. To explore whether curcumin can inhibit hyperandrogen-induced ER stress in ovarian GCs of PCOS rats and to elucidate the possible underlying mechanisms. We developed PCOS model rats by exposure to hyperandrogenic conditions and divided the rats into control, PCOS, and PCOS+curcumin (200 mg/kg, for 8 weeks) groups. The levels of ER stress-related proteins and PI3K/AKT phosphorylation were measured in the ovarian tissue of all experimental groups by real-time quantitative PCR, western blotting, immunohistochemistry, and immunofluorescence. Subsequent in vitro analysis on primary cultured GCs was performed to confirm the influence of curcumin on ER stress inhibition by immunofluorescence and western blotting. Curcumin protects GCs from hyperandrogen-induced apoptosis in PCOS model rats by inhibiting the ER stress-related IRE1α-XBP1 pathway and activating the PI3K/AKT signaling pathway. These observations indicate that curcumin might be a safe and useful supplement for PCOS patients.