Amelioration of Cisplatin-Induced kidney injury by Arabinogalactan based on network pharmacology and molecular docking

Cisplatin is the most widely used anticancer chemotherapy drug at present. However, its severe nephrotoxic side effects limit the clinical application. This study aimed to investigate the potential protective mechanism of arabinogalactan (AG) on acute kidney injury (AKI) induced by cisplatin in mice. Firstly, 105 potential targets of AG were predicted by using the SwissTargetPrediction database, 25,183 kidney disease targets were obtained by searching 5 disease databases, and 100 cross-target targets were obtained by drawing a Venn diagram. We constructed the AG-Key target interaction network and PPI protein interaction network of cross-targets and screened out 21 core targets. Through the GO and KEGG enrichment analysis of the core targets, we can found that the core targets involved a total of 1254 biological functions and 56 signaling pathways, including the apoptosis signaling pathway. By establishing an animal model in vivo, we found that pretreatment with AG at doses of 200 and 400 mg/kg could decrease the kidney index, such as serum creatinine (CRE), and blood urea nitrogen (BUN) levels induced by cisplatin, and reduce the kidney histopathology injury. Importantly, AG could inhibit the formation of metaldehyde (MDA) and 4-hydroxynonenal (4-HNE) in the kidney tissues and reduce the oxidative stress injury induced by cisplatin. Meanwhile, AG also restored the expression of anti-apoptotic pro-teins Bcl-2 and Bcl-xL and decreased the expression of pro-apoptotic proteins Bax and Bad in cisplatin-induced renal tissues. Finally, AG could further reduce cisplatin-induced kidney cell apoptosis.

Automated summary

This study investigated the potential protective mechanism of arabinogalactan (AG) on acute kidney injury (AKI) induced by cisplatin in mice. The results showed that pretreatment with AG could reduce kidney injury and oxidative stress induced by cisplatin, as well as restore the expression of anti-apoptotic proteins and decrease the expression of pro-apoptotic proteins in renal tissues.