Journal
JOURNAL OF ETHNOPHARMACOLOGY
Volume 280, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2021.114411
Keywords
Yi-Qi-Jian-Pi formula; Network pharmacology; Apoptosis; Liver failure; Hypoxic liver injury
Categories
Funding
- Leading Talent Project of Jiangsu Province Traditional Chinese Medicine [SLJ0216]
- Scientific Foundation of Nanjing Hospital of Chinese Medicine [YJJC201909]
- Scientific project of Health Science and technology development in Nanjing health committee [YKK20163]
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YQJPF ameliorates liver injury by suppressing hypoxic injury and ROS-mediated hepatocyte apoptosis through modulating the PI3K/AKT pathway.
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 CCl4-, 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-1 alpha 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.
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