Targeting HMGB1/PI3K/Akt and NF-κB/Nrf-2 signaling pathways by vildagliptin mitigates testosterone-induced benign prostate hyperplasia in rats

Benign prostatic hyperplasia (BPH) is a prevalent illness in older adults. It is well-recognized that testosterone is essential in the onset of BPH. Vildagliptin (Vilda), a dipeptidyl peptidase-IV inhibitor, has been shown to have anti-inflammatory and antioxidant effects. In this study, we studied the effects of vildagliptin on testosterone-induced BPH in rats and its underlying mechanisms. Forty male Wistar rats were allocated into four groups (n = 10): CTRL, Vilda, BPH, and BPH + Vilda groups. Our results revealed that vildagliptin treatment considerably lessened the prostate weight, prostate index, serum levels of prostate-specific antigen, 5α-reductase activity, and DHT levels compared to the testosterone group. Furthermore, vildagliptin treatment inhibited the expression of HMGB1, PI3K/Akt/NF-κB, and TNF-α signaling pathways in the prostate tissue of diseased rats. Additionally, vildagliptin treatment increased the expression of Nrf-2 and HO-1, reduced GSH levels, and lowered MDA levels. Besides, vildagliptin noticeably scaled up the level of cleaved caspase-3 enzyme and, conversely, the protein expression of proliferating cell nuclear antigen (PCNA). Correspondingly, vildagliptin counteracts testosterone-induced histological irregularities in rats' prostates. These findings suggest that vildagliptin may be a potential prophylactic approach to avoid BPH. •Benign prostatic hyperplasia (BPH) is a prevalent urological condition.•Vildagliptin, a dipeptidyl peptidase-IV inhibitor, has been shown to have anti-inflammatory and antioxidant effects.•Testosterone-induced benign prostatic hypertrophy resulted in modification of HMGB/PI3K/Akt/ signaling was linked with increased ROS production and inflammation and may result in benign prostate enlargement.•vildagliptin guarded rats against testosterone-induced benign prostatic hyperplasia. These potential advantages were achieved mainly by blocking the activation of HMGB1/PI3K/Akt and enhancing the Nrf-2/HO-1 pathway