Exploring Nephroprotective Properties of <i>Wedelia chinensis: In Vitro, In Silico,</i> and <i>In Vivo</i> Investigations

Abstract

The purpose of this research work is to investigate the nephroprotective efficacy of Wedelia chinensis leaf extracts against gentamicin-induced nephrotoxicity for in vitro, in silico, and in vivo techniques. The extracts of Wedelia chinensis leaf rich in flavonoids were subjected to an in silico method for ligands and target proteins. The results of the in vitro antioxidant study of extracts were tested for cytoprotective MTT assay and anti-inflammatory efficacy by protein denaturation assay using Human Embryonic Kidney cells (HEK293). The in vivo nephroprotective potential of the extract was evaluated with the two doses of 250mg/kg and 500mg/kg body weight in gentamicin nephrotoxicity in rats. The biochemical parameters observed for changes in the histopathology of the kidney. While comparing with other extracts of Wedelia chinensis Hydroalcoholic Extract (WCHAE) shows great binding affinity with bonding interactions of flavonoids and phenolics-based ligands observed with the target proteins that provided early information. The in vitro cell lines study revealed no cytotoxicity and better anti-inflammatory effect on HEK293 cells with cytoprotective and nephroprotective efficacy of WCHAE. The in vivo nephroprotective activity improved at a dose of 500mg/kg of WCHAE than Wedelia chinensis Ethanolic Extract (WCEE). The histopathological findings revealed the improvement in gentamicin-induced renal toxicity by the WCHAE orally treated group compared to normal and negative control groups. These results of WCHAE are more satisfactorily effective than WCEE with marked in vitro antioxidant, and cytoprotective effects in HEK293 cells. In in silico docking, it shows good interaction scores of ligands for target proteins like (kidney injury molecule) KIM-1 and Neutrophil Gelatinase-Associated Lipocalin (NAGAL) that helps to correlate nephroprotective potential benefits of antioxidants in plant extracts against gentamicin induced nephrotoxicity in rats.