Yi-Qi-Jian-Pi formula modulates the PI3K/AKT signaling pathway to attenuate acute-on-chronic liver failure by suppressing hypoxic injury and apoptosis in vivo and in vitro

  • J Ethnopharmacol. 2021 Nov 15;280:114411. doi: 10.1016/j.jep.2021.114411.
Li Tang  1 ,  Feixia Wang  2 ,  Lingyan Xiao  3 ,  Min Shen  4 ,  Siwei Xia  4 ,  Zili Zhang  4 ,  Feng Zhang  4 ,  Shizhong Zheng  4 ,  Shanzhong Tan  5
Affiliations
  • 1. Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China; Department of Gastroenterology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210001, China. Electronic address: [email protected].
  • 2. Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Material Medical, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 3. Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China.
  • 4. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Material Medical, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 5. Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China. Electronic address: [email protected].
PMID: 34265380 DOI: 10.1016/j.jep.2021.114411
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 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-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.

Keywords
Apoptosis; Hypoxic liver injury; Liver failure; Network pharmacology; Yi-Qi-Jian-Pi formula.
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