Cryptotanshinone alleviates polycystic ovary syndrome in rats by regulating the HMGB1/TLR4/NF-κB signaling pathway

Cryptotanshinone (CRY) has been demonstrated to reverse reproductive disorders. However, whether CRY is effective in the treatment of polycystic ovary syndrome (PCOS) remains unknown. The aim of the present study was to evaluate the therapeutic potential of CRY in PCOS. A rat model of PCOS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. Total body weight and ovarian weight, as well as the levels of luteinizing hormone (LH) and the LH to follicle-stimulating hormone (FSH) ratio (LH/FSH) significantly increased in rats with PCOS, compared with controls. Moreover, the levels of testosterone (T), tumor necrosis factor (TNF)-α and high-mobility group box 1 protein (HMGB1) also increased. However, CRY treatment attenuated the increase in body weight, ovarian weight, LH, LH/FSH ratio, T, TNF-α and HMGB1 levels, compared with the PCOS group. Treatment with CRY also reduced NF-κB/p65, HMGB1 and toll-like receptor (TLR)4 mRNA and protein expression levels in the ovarian tissue and granulosa cells, both in vitro and in vivo. Thus, CRY significantly mitigated the changes in body weight, ovary weight, hormone levels and inflammatory factor levels observed in rats with PCOS. Thus, CRY protects against PCOS-induced damage of ovarian tissue, possibly through a regulatory pathway involving HMGB1, TLR4 and NF-κB.