A potent protective effect of baicalein on liver injury by regulating mitochondria-related apoptosis

Apoptosis. 2020 Jun;25(5-6):412-425. doi: 10.1007/s10495-020-01608-2.

Abstract

Liver injury is the early stage of liver disease, which is caused by multiple factors. Baicalein has shown extensive bioactivity. But whether baicalein has a protective effect on liver injury has not been reported thus far. In this study, we aim to investigate the protective effects of baicalein on liver injury induced by oxidative stress. H2O2 and CCl4 were employed to establish liver injury models in vivo and in vitro, respectively. The protective effect of baicalein on oxidative stress-induced liver injury was evaluated by detecting the mitochondrial dynamics, the level of autophagy and apoptosis, the histopathology of liver, the indicators of liver function, and the level of oxidative stress in vitro and in vivo. March5 is the key regulator during liver injury induced by oxidative stress. March5 can ubiquitinate Drp1 and promote Drp1 degradation, then maintain the homeostasis of mitochondrial dynamics, keep the balance of autophagy, and reduce apoptosis. Baicalein is able to effectively reduce liver injury; it can contribute to the expression of March5 by regulating KLF4 during liver injury. These results indicate that baicalein plays a key role in salvaging liver from injury induced by oxidative stress via regulating the KLF4-March5-Drp1 signal pathway.

Keywords: Apoptosis; Baicalein; Liver injury; March5; Mitochondrial dynamics; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Carbon Tetrachloride / administration & dosage
  • Carbon Tetrachloride / antagonists & inhibitors*
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / genetics*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Dynamins / genetics
  • Dynamins / metabolism
  • Flavanones / pharmacology*
  • Gene Expression Regulation
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / pharmacology
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Mitochondrial Dynamics / drug effects
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antioxidants
  • Bax protein, mouse
  • Flavanones
  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Mitochondrial Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Bcl2 protein, mouse
  • baicalein
  • Hydrogen Peroxide
  • Carbon Tetrachloride
  • Marchf5 protein, mouse
  • Ubiquitin-Protein Ligases
  • Dnm1l protein, mouse
  • Dynamins