Bergenia ciliata Root Extract Attenuates Artesunate-Induced Hepatotoxicity via Dual Modulation of Oxidative Stress and Apoptotic Signaling: An In Vitro and In Vivo Study.

Artesunate (ART), a widely used antimalarial drug, has been associated with hepatotoxic effects when administered at supratherapeutic doses over prolonged durations. This study aimed to elucidate the biochemical and molecular mechanisms underlying ART-induced liver injury and to evaluate the hepatoprotective potential of Bergenia ciliata root extract (BCRE) as a cotreatment, using a combination of in vitro and in vivo approaches. B. ciliata was selected based on its well-documented antimalarial activity and hepatoprotective properties. In vitro cytotoxicity was assessed by determining the IC50 value, while in vivo hepatotoxicity was induced in an experimental animal model through supratherapeutic ART administration. ART-treated animals exhibited a significant elevation in hepatic enzyme levels, increased oxidative stress markers, pronounced histopathological damage, upregulation of the pro-apoptotic marker Caspase-3, and downregulation of the antiapoptotic marker Bcl-2, collectively indicating activation of the apoptotic pathway. Coadministration of BCRE significantly attenuated all of these biochemical, histopathological, and apoptotic alterations in a dose-dependent manner, with the high-dose BCRE group demonstrating a level of hepatoprotection comparable to the standard positive control, silymarin. These findings suggest that BCRE confers hepatoprotection against ART-induced liver injury through dual mechanisms: attenuation of oxidative stress and inhibition of apoptosis, supporting its potential as a safe and effective adjunct to ART-based antimalarial therapy.