ArticleFrontiers in pharmacology2026
Protective role of
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Artesunate (ART) is a widely used antimalarial agent; however, dose-dependent nephrotoxicity limits its clinical utility. Bergenia Ciliata, a medicinal plant with established renoprotective traditional use, was investigated as a potential nephroprotective agent against ART-induced kidney injury. Methods: Bioactive metabolites from B. ciliata root extract were identified via Gas Chromatography-Mass Spectrometry (GC-MS) and filtered through in silico ADME profiling. Network pharmacology was employed to identify key hub genes implicated in ART-induced renal injury, with PPARγ emerging as the primary therapeutic target. Molecular docking and 200 ns molecular dynamics simulations were performed to evaluate binding affinity and complex stability. Cytotoxicity was assessed using the MTT assay on HEK293 cells. In vivo nephroprotective activity was evaluated in Wistar albino rats administered high-dose ART (150 mg/kg), with or without B. Ciliata root extract (200 and 400 mg/kg). Results: Rutin (CID 5280805) demonstrated the highest docking score (-10.307 kcal/mol) and binding affinity (MM-GBSA: -71.66 kcal/mol) against PPARγ, with stable complex dynamics confirmed over 200 ns. B. ciliata extract showed negligible cytotoxicity (>90% cell viability across all concentrations). In vivo, co-administration of B. Ciliata with ART significantly reduced elevated serum urea, uric acid, and creatinine levels in a dose-dependent manner, with the 400 mg/kg dose producing the most pronounced renoprotection. Histopathological evaluation confirmed measurable recovery of renal tissue architecture. Discussion: The integrated in-silico and experimental findings suggest that B. Ciliata root extract exerts nephroprotective effects against ART-induced kidney injury, likely through PPARγ activation mediated by rutin. The combination of B. Ciliata with ART demonstrated superior renoprotection compared to silymarin, supporting its potential as a complementary therapeutic strategy in high-dose antimalarial regimens.
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