Investigation of cisplatin-induced acute kidney injury using LC-HRMS and network pharmacology approaches in mixed Curcuma longa and Curcuma zedoaria eExtracts.

Background: Cisplatin-induced acute kidney injury (AKI) is a serious complication of cancer therapy. Natural compounds, such as those found in Curcuma species, may exert protective effects through anti-inflammatory and antioxidant mechanisms. Aim: This study investigated the therapeutic mechanisms of combined Curcuma longa and Curcuma zedoaria extracts against cisplatin-induced kidney damage using Ultra-High Performance Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS) and network pharmacology. Methods: An ethanolic extract was prepared and analyzed using UHPLC-Q-Orbitrap HRMS to identify active compounds. The antioxidant capacity was assessed using the Diphenyl-2-picryl-hydrazyl assay. Network pharmacology was used to predict compound-target interactions and identify key proteins involved in AKI pathways. Results: UHPLC-Q-Orbitrap HRMS analysis identified 40 bioactive compounds, among which 22 met the OB >30% threshold. Network analysis revealed 14 overlapping protein targets associated with AKI from 485 compound-related targets and 198 disease-related targets. Conclusion: This study demonstrated that key phytochemicals in C. longa and C. zedoaria may act on multiple protein targets implicated in AKI, highlighting their potential as multitarget therapeutics for kidney protection and future drug development.