Benzyl salicylate from the stems and stem barks of Cornus walteri as a nephroprotective agent against cisplatin-induced apoptotic cell death in LLC-PK1 cells

Nephrotoxicity currently plagues the therapeutic use of cisplatin. Its major side effects are predominantly associated with renal tubular cell apoptosis. In this study, we examined the potential nephroprotective constituents from C. walteri that can exert effects against cisplatin-induced oxidative stress and apoptosis in renal tubular epithelial (LLC-PK1) cells. Phytochemical investigation of the MeOH extract of the stems and stem barks of C. walteri led to the isolation of the potential nephroprotective constituents (1–15). Among the isolates, treatment with benzyl salicylate (BS) (15) (50 and 100 μM) significantly attenuated LLC-PK1 cell apoptosis and potently blocked cisplatin-induced nuclei condensation, intracellular ROS generation, and apoptosis, as indicated by Hoechst 33342 and H(2)DCFDA staining. Furthermore, the expression of apoptosis-related proteins such as MAPK, Bax/Bcl-2 protein ratio, and cleaved caspase-9 and -3, were significantly decreased by BS. These findings provide that benzyl salicylate can be a nephroprotective agent against cisplatin-induced oxidative stress and apoptosis.