Protective effect of Satureja montana extract on cyclophosphamide-induced testicular injury in rats

•This is the first demonstration of testicular protective effect of Satureja montana.•Satureja montana ameliorates cyclophosphamide-induced testicular injury in rats.•Satureja montana exerts its protection via antioxidant & anti-apoptotic mechanisms.•Satureja montana restores cyclophosphamide-lowered serum testosterone level.•Satureja montana upregulates cyclophosphamide-lowered testicular PPAR-γ & Akt1. The present study investigated the protective effect of Satureja montana extract against cyclophosphamide-induced testicular injury in rats. Total phenolic and flavonoid contents of the extract were 1.03% and 0.34%w/w of dry herb expressed as chlorogenic acid and quercetin, respectively. HPLC analysis identified caffeic, syringic and rosmarinic acids as the chief phenolic acids, and rutin as the major flavonoid in the extract. Oral daily administration of S.montana extract (50mg/kg/day) for 7days before and 7days after an intraperitoneal injection of cyclophosphamide (200mg/kg) restored the reduced relative testicular weight, serum testosterone level and testicular alkaline phosphatase activity, raised the lowered testicular sorbitol dehydrogenase and acid phosphatase activities, and decreased the elevated testicular hemoglobin absorbance. It also attenuated lipid peroxidation, restored the lowered glutathione content, glucose-6-phosphate dehydrogenase, glutathione peroxidase and glutathione reductase activities, and improved total antioxidant capacity. Moreover, S.montana extract mitigated testicular DNA fragmentation, decreased the elevated Fas and Bax gene expression, up-regulated the decreased Bcl-2 and peroxisome proliferator-activated receptor-gamma (PPAR-γ) gene expression and normalized Akt1 protein level. Histopathological investigation confirmed the protective effects of the extract. Conclusively, S.montana extract protects the rat testis against cyclophosphamide-induced damage via anti-oxidative and anti-apoptotic mechanisms that seem to be mediated, at least in part, by PPAR-γ and Akt1 up-regulation.