Unveiling pharmacological targets of Rihimaside C for radiation-induced lung injury: An in silico and experimental integrated approach.

BACKGROUND AND AIM: Radiation-induced lung injury (RILI) is a common complication during caner radiotherapy, mainly characterized by oxidative stress and inflammation. Rihimaside C, a novel dihydroflavonol compound isolated from Ribes himalense, exhibits significant anti-inflammatory and antioxidant properties. The study aims to investigate the therapeutic efficacy of Rihimaside C in treating RILI, as well as to uncover the potential targets and mechanisms involved. EXPERIMENTAL PROCEDURE: Animal experiments were performed to evaluate the pharmacological efficacy of Rihimaside C for RILI. A computer-based strategy was employed to retrieve and screen potential targets for the therapy of Rihimaside C against RILI. STRING, DAVID databases, and Cytoscape software were utilized to construct a protein-protein interaction network and identify hub targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to illuminate the underlying mechanisms. Molecular docking and Cellular Thermal Shift Assay (CETSA) were performed to further validate the hub targets. RESULTS AND CONCLUSION: The results of animal experiments showed that Rihimaside C effectively alleviated RILI. Four hub targets (TNF, HSP90AA1, ESR1 and HIF1A) among the 72 possible targets of Rihimaside C involved in the treatment of RILI were finally identified through network pharmacology, which were enriched in MAPK, IL-17, and PI3K/Akt signaling pathways. Molecular docking and CETSA analyses indicated that HSP90AA1 displayed highest binding affinity with Rihimaside C. This study investigated the therapeutic effects of Rihimaside C on RILI and identified potential targets, providing a novel strategy in treating RILI.