To explore the effects of geniposide on insulin resistance and oxidative stress damage in polycystic ovary syndrome (PCOS) rats by regulating the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) signaling pathway.

A PCOS model was induced by gavage of letrozole for 21d and rats were randomly assigned into blank group (not modeled +normal saline), model group (modeled +normal saline), low-dose geniposide group (modeled+400 mg·kg^-1 geniposide by gavage), high-dose geniposide group (modeled+800 mg·kg^-1 geniposide by gavage), positive control group (modeled+0.34 mg·kg^-1 ethinylestradiol and cyproterone by gavage) and high-dose geniposide+ML385 group (modeled+800 mg·kg^-1 geniposide by gavage+30 mg·kg^-1 ML385 by by intraperitoneal injection), with 10 rats in each group. The levels of fasting blood glucose (FBG) and fasting insulin (FINS) were measured by blood glucose meter and enzyme-linked immunosorbent assay (ELISA) and then homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. The levels of serum sex hormones and inflammatory were detected by ELISA and ovarian tissue oxidative stress index levels were detected by test kit, hematoxylin-eosin (HE) staining was used to measure the number of cystic follicles in rat ovarian tissue. TdT-media duTP nict end labeling (TUNEL) method was used to measure apoptosis of rat ovarian granulosa cells. Moreover, Western blot (WB) was used to detect apoptosis and Nrf2/HO-1 signaling pathway related protein expression in ovarian tissues.

The FBG levels in the low-dose geniposide group, high-dose geniposide group, positive control group, high-dose geniposide+ML385 group and control group, as well as the model group were (6.87±0.42), (5.21±0.28), (5.03±0.31), (8.32±0.51), (4.90±0.35) and (8.56±0.54) mmol·L^-1, respectively; FINS were (16.13±1.62), (10.46±1.37), (10.21±1.51), (20.67±1.82), (9.82±1.14) and (21.45±2.05) mIU·L^-1, respectively; HOMA-IR were 4.93±0.48、2.42±0.53、2.28±0.36、7.64±0.72、2.14±0.31 and 8.16±0.67, respectively; follicle-stimulating hormone (FSH) levels were (5.14±0.56), (7.49±0.62), (7.62±0.71), (2.95±0.54), (7.83±0.76) and (2.71±0.43) IU·L^-1, respectively; the superoxide dismutase (SOD) levels were (42.91±3.22), (56.45±4.16), (58.02±3.98), (32.16±2.85), (59.73±4.35) and (30.84±2.74) U·mg prot^-1, respectively. The relative protein expression levels of Nrf2 were 0.67±0.08, 1.10±0.12, 1.12±0.13, 0.26±0.07, 1.13±0.14 and 0.24±0.06, respectively; HO-1 were 0.61±0.07, 1.06±0.08, 1.08±0.10, 0.18±0.05, 1.09±0.11 and 0.16±0.04, respectively. The malondialdehyde (MDA) levels were (2.47±0.33), (1.39±0.21), (1.30±0.19), (3.38±0.42), (1.21±0.26) and (3.62±0.47) nmol·mg prot^-1, respectively. The number of ovarian antral follicles was 9.60±0.74, 4.30±0.57, 4.10±0.71, 14.20±0.98, 3.90±0.65 and 15.10±1.13, respectively. The ovarian granulosa cell apoptosis index was (16.27±1.16)%, (7.48±0.91)%, (7.19±0.76)%, (23.86±1.23)%, (6.94±0.85)% and (25.31±1.42)%, respectively. Compared blank group with the control group; compared model group with low-dose geniposide group, high-dose geniposide group and positive control group; compared low-dose geniposide group with high-dose geniposide group and compred high-dose geniposide group with high-dose geniposide+ML385 group, the differences of above indexes were all statistically significant (all P<0.05).

Geniposide can alleviate insulin resistance and oxidative stress damage in PCOS rats, possibly by activating the Nrf2/HO-1 signaling pathway.