Berberine protects acute liver failure in mice through inhibiting inflammation and mitochondria-dependent apoptosis.

Abstract

Acute liver failure (ALF) is characterized by sudden large area of inflammation and extensive hepatocyte apoptosis. This study identified the natural product berberine as a potential agent for acute liver failure(ALF). First, in vitro, BBR pre-incubation (5, 10 and 20μM) alleviated L02 hepatocytes injury induced by D-GalN (5mM)/TNF-α (100ng/ml). Second, in vivo, BBR pre-treatment attenuated D-Galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver failure, as evidenced by the reduction of mortality, the alleviation of liver pathological changes and the inhibition of alanine aminotransferase (ALT)/aspartate aminotransferase (AST). Our results further illustrated that BBR inhibited the nuclear translocation of NF-κB p65 and subsequently suppressed the expressions of inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at both mRNA and protein levels in ALF. Moreover, western blotting demonstrated that BBR effectively inhibited apoptosis via reducing cytochrome c release, Bax/Bcl-2 ratio and caspase-3/-9 cleavage in vitro and in vivo. In conclusion, our findings suggest that BBR serves as a potential agent for preventing or treating human ALF by inhibiting inflammation and mitochondria-dependent apoptosis.

• Authors: Lulu Xu, Xia Zheng, Yinhang Wang, Qilin Fan, Miao Zhang, Ruiyan Li, Junmei Ye, Xiaojun Wu, Wenfeng Zhao, Yubin Zhang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 819 Pg. 161-168 (Jan 15 2018) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 29191769 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• NF-kappa B
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Berberine
• Galactosamine

Topics

• Animals
• Apoptosis (drug effects)
• Berberine (pharmacology, therapeutic use)
• Cytoprotection (drug effects)
• Galactosamine (pharmacology)
• Inflammation (drug therapy)
• Liver Failure, Acute (metabolism, pathology, prevention & control)
• Male
• Mice
• Mice, Inbred ICR
• Mitochondria (drug effects, metabolism)
• NF-kappa B (metabolism)
• RAW 264.7 Cells
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)