α-Mangostin, a Dietary Xanthone, Exerts Protective Effects on Cisplatin-Induced enal Injury via PI3K/Akt and JNK Signaling Pathways in HEK293 Cells

Abstract

Previous report has confirmed the beneficial effects of α-mangostin (α-MG), a major and representative xanthone distributed in mangosteen (Garcinia mangostana) on the cisplatin-induced rat model. However, the molecular mechanisms related to its renoprotection have not been elucidated exhaustively. The present study investigated the protective effect of α-MG against cisplatin-induced cytotoxicity in the human embryonic kidney (HEK293) cell model. In this study, α-MG prevented cisplatin-induced cell death, accompanied with the decreased levels of malondialdehyde and increased glutathione content. Particularly, α-MG significantly suppressed the overproduction of reactive oxygen species (OS), restored the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and downregulated the c-JUN N-terminal kinase (JNK) pathways following cisplatin challenge. Subsequently, the cleavage of caspases and poly-ADP-ribose polymerase (PAP) implicating OS-mediated apoptosis pathways induced by cisplatin was effectively inhibited by α-MG. In conclusion, our findings provided a rationale for the development of α-MG to attenuate cisplatin-induced nephrotoxicity.