Protective Effect of Mangiferin on Cisplatin Induced Acute Kidney Injury in Vivo

Background : Cisplatin is a cytotoxic compound that has low selectivity to cancer cells and may cause serious adverse reactions, including acute kidney injury (AKI). Oxidative stress and inflammation are the main causes of cisplatin-induced AKI (CIAKI). Mangiferin is a polyphenolic xanthonoid that possesses extraordinary antioxidant and anti-inflammatory properties. The purpose of this investigation was to ascertain the potential renal protective mechanism of mangiferin in alleviating CIAKI. Methods : We assayed serum creatinine levels, histopathological changes and KIM-1 expression to evaluate the kidney injury. The expression of inflammatory factors was detected by Cytokine Immunoassay, pathological immunohistochemistry and immunofluorescence staining to evaluate the inflammatory response. DNA microarray analysis and network pharmacology were used to explore the effect of mangiferin on CIAKI. Results : We found that mangiferin decreased serum creatinine and KIM-1 in CIAKI mice. In renal tissue of CIAKI mice, inflammatory cells infiltrated and IL-2, IL-13, MCP-1, MIP-1α and KC levels increased, while the IL-10 level decreased. These changes reversed after mangiferin treatment. The network pharmacology results indicated that the protective effect of mangiferin against CIAKI was mediated by the interplay of cytokines, their receptors, and the chemokine signal transduction. Pathological analysis showed that changes in the expression of F4/80, IL-2, IL-9, MMP13, MCP-1, CSF-1, NF-κB, and MIP-1α were significantly reversed by mangiferin treatment. Conclusion : Therefore, we speculate that the anti-inflammatory effect of mangiferin is mediated by the regulation of macrophages in alleviating CIAKI.