Improvement of Cisplatin-induced renal dysfunction by Schisandra chinensis stems via anti-inflammation and anti-apoptosis effects

Abstract

Ethnopharmacological relevanceSchisandra chinensis (Turcz.) Baill is a frequently used traditional Chinese medicine, and modern pharmacological research has proven that S. chinensis has antioxidant, anti-hepatotoxity, anti-inflammatory, and anti-nephrotoxic effects. Cisplatin is widely used as antineoplastic drug at present, but the clinical application is limited owing to its nephrotoxicity. Aim of the studyTo demonstrate the renoprotective activity of the extract of the stems of S. chinensis (SCE) in mice established by cisplatin-triggering acute kidney injury (AKI). The possible molecular mechanism of nephroprotection exhibited by SCE was evaluated for the first time. Materials and methodsMice in SCE groups were pre-treated with SCE for 10 consecutive days, and on 7th day 1 h after final administration, following intraperitoneal injection of cisplatin with 20 mg/kg was treated to cisplatin group and SCE groups. On the 10th day, renal function, histopathological change, and oxidative stress markers were investigated. ResultsRenal oxidative stress level characterized by elevated heme oxygenase 1 (HO-1), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) expression was obviously reduced by SCE pre-treatment. In addition, SCE was found to suppress inflammatory response through the reduction of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-κB) p65 activation. SCE treatment also inhibited activation of apoptotic pathways through down-regulating Bax, cleaved caspase-3, 8, 9 and up-regulating Bcl-2 expression levels. ConclusionThese findings illustrated that SCE possessed powerful protective effect on AKI caused by cisplatin via amelioration of oxidative stress, inflammation and apoptosis.