Abstract

Ethnopharmacological relevance Acute-on-chronic liver failure (ACLF) is a key complication of chronic hepatitis, with a relatively high mortality rate and limited treatment options, which dramatically threatens human lives. Yi-Qi-Jian-Pi formula (YQJPF) is a herbal compound commonly used to treat liver failure. Aim of the study The purpose of this research is to discuss the potential molecular biological effect and mechanism of YQJPF in ACLF. Materials and methods In this study, we created a rat model of ACLF by CCl 4 -, LPS- and D-Galactosamine (D-Gal) and an in vitro model of LPS-induced hepatocyte damage. The specific components of YQJPF and potential mechanism were explored based on bioinformatics analyses. Furthermore, we verified the effect of YQJPF on ACLF using immunohistochemistry, RT-qPCR, western blotting , and flow cytometry. Results Our research demonstrated that, after YQJPF treatment, hepatocyte injury in rats was relieved. Bioinformatics analysis showed that PI3K/AKT, HIF-1, mitochondrial apoptosis pathways played prominent roles. YQJPF promoted HIF-1α protein expression and exerted protective effects against hypoxic injury, simultaneously reducing mitochondrial ROS production, suppressing hepatocyte apoptosis. Furthermore, we showed that YQJPF accelerates PI3K/AKT pathway activation, a known broad-spectrum inhibitor of PI3K. LY294002 , which was used for reverse verification, suppressed the effect of YQJPF on hypoxic injury and ROS-mediated hepatocyte apoptosis. Conclusions YQJPF ameliorates liver injury by suppressing hypoxic injury and ROS-mediated hepatocyte apoptosis by modulating the PI3K/AKT pathway.