Celastrol attenuates testosterone-induced benign prostatic hyperplasia by modulating the PTEN/PI3K/AKT pathway

Benign prostatic hyperplasia (BPH) represents a prevalent urological disease observed primarily among aging men. Celastrol (CELA) is an active natural compound with diverse pharmacological properties. The primary aim of this research is to assess the potential protective activity of CELA in testosterone (TEST)-induced BPH in rats. Male Wistar rats were allocated into six distinct groups for treatment: group 1 acted as the control and was given the vehicle; group 2 received only CELA (2 mg/kg, orally); group 3 was administered TEST alone (3 mg/kg, subcutaneously); groups 4 and 5 were administered the combination of TEST (3 mg/kg, subcutaneously) and CELA (1 or 2 mg/kg, orally); and group 6 received a combination of TEST (3 mg/kg, subcutaneously) and finasteride (FINA) (0.5 mg/kg, orally). Over a period of four weeks, CELA at doses of 1 or 2 mg/kg effectively inhibited the increase in both the prostate index and weight when compared to rats treated with TEST. CELA mitigated pathological alterations in prostate architecture, reduced the proliferation markers and modulated the expression of apoptosis markers compared to TEST-treated rats. Furthermore, CELA exhibited antioxidant properties by mitigating the TEST-induced increase in lipid peroxide levels and the depletion of superoxide dismutase and catalase activities. Moreover, CELA exhibited anti-inflammatory activity by significantly downregulating tumor necrosis factor-α, interleukin-6, and nuclear factor-κB expression. In addition, CELA elevated phosphatase and tensin homolog (PTEN) and reduced phosphatidylinositol 3-kinase (PI3K) and AKT expression compared with the TEST group. In addition, CELA inhibited TEST-induced enhancement of mRNA expression of 5α-reductase type 2, androgen receptor and fibroblast growth factor 2. Overall, CELA partially alleviates TEST-induced BPH in rats, an effect that is associated with modulation of PTEN/PI3K/AKT axis.