Sida cordifolia L. fraction ameliorate renal injury, inflammation, apoptosis and gene expression on cisplatin induced acute kidney injury: Network pharmacology, in vivo and in vitro studies.

Abstract

Background: Acute kidney injury (AKI) is known to involve oxidative stress, apoptosis and inflammation and becoming global health issue. Sida cordifolia L. is a medicinal plant having numerous pharmacological proper ties. The purpose of this study is to determine the presence of bioactive compounds in the chloroform fraction of Sida cordifolia L. (CFSC), and its effectiveness against cisplatin-induced AKI. Methods: HPLC and ESI–MS studies were used to examine the presence of bioactive components in CFSC. Further network pharmacology study was done by using SwissTargetPrediction, GeneCards, and the string database. The renal protection by CFSC was investigated on cisplatin induced NRK-52E cells and in vivo experimentation. Cell viability by MTT assay and apoptosis parameters were performed by DAPI and AO/EB staining. Biochemical parameter was performed to evaluate renal function, protein expression and mRNA expression of related gene and histopathological analysis was done by H & E and PAS staining. Results: CFSC contains Galangin, Naringenin, (-)-Epiafzelechin, Glycitein, 5,7-Dimethoxyflavanone and Sakuranetin as suggested by ESI-MS library analysis. The network pharmacology results suggest that numerous factors cause pathogenesis of AKI is complex. KEGG enrichment analysis showed the majority of pathways mentioned were closely related to various signaling pathways like ROS. Cell viability and apoptosis reported that CFSC could reduce cisplatin-treated cell death and apoptosis and the levels of kidney injury markers, flammatory lipid peroxidation markers, and increase antioxidant markers. Conclusion: CFSC could able to protect against renal injury, inflammation, and apoptosis from cisplatin-induced cytotoxicity and arrest the inflammation and signaling cascades of apoptosis.