Alantolactone prevents testosterone-induced benign prostatic hyperplasia in rats via modulation of PTEN/PI3K/AKT axis

Current treatment options for benign prostatic hyperplasia (BPH) suffer intolerable adverse effects. The goal of this investigation was to evaluate the possible protective effects of alantolactone (ALA) in testosterone (TEST)-induced BPH in rats. Wistar rats were grouped into 5 batches namely; Control, ALA (10 mg/kg), TEST, TEST + ALA (5 mg/kg) and TEST + ALA (10 mg/kg). Co-treatment of ALA at both doses significantly prevented TEST-induced increase in prostate index and histopathological alteration. Further, ALA exhibited potent antioxidant properties shown by lipid peroxidation inhibition and antioxidant enzymatic activity exhaustion in prostatic tissues. Also, ALA significantly inhibited immuno-expression of inflammatory markers including nuclear factor kappa B, tumor necrosis factor-α and interleukin-6. Pro-apoptotic activities of ALA were proven by its ability to prevent TEST-induced Bax down-regulation and Bcl-2 up-regulation. This was associated with enhancement of prostatic PTEN as well as inhibition of PI3K and p-AKT immuno-expression. Thus, ALA displayed a protective activity against a rat model of TEST-induced BPH. This may be attributed to its antioxidant, antiproliferative, pro-apoptotic and anti-inflammatory activities. Furthermore, it has been linked to its ability to modulate PTEN/PI3K/AKT axis.