Danshen protects against early-stage alcoholic liver disease in mice via inducing PPARα activation and subsequent 4-HNE degradation

PLoS One. 2017 Oct 11;12(10):e0186357. doi: 10.1371/journal.pone.0186357. eCollection 2017.

Abstract

Alcoholic liver disease (ALD) is a type of chronic liver disease caused by long-term heavy ethanol consumption. Danshen is one of the most commonly used substances in traditional Chinese medicine and has been widely used for the treatment of various diseases, and most frequently, the ALD. The current study aims to determine the potential beneficial effect of Danshen administration on ALD and to clarify the underlying molecular mechanisms. Danshen administration improved liver pathologies of ALD, attenuated alcohol-induced increment of hepatic 4-Hydroxynonenal (4-HNE) formation, and prevented hepatic Peroxisome proliferators activated receptor alpha (PPARα) suppression in response to chronic alcohol consumption. Cell culture studies revealed that both hepatoprotective effect and increased intracellular 4-HNE clearance instigated by Danshen supplementation are PPARα-dependent. In conclusion, Danshen administration can protect against ALD via inducing PPARα activation and subsequent 4-HNE degradation.

MeSH terms

  • Alcoholism / drug therapy
  • Alcoholism / metabolism
  • Alcoholism / pathology
  • Aldehydes / metabolism*
  • Animals
  • Cell Death / drug effects
  • Dietary Supplements
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Ethanol / administration & dosage
  • Hep G2 Cells
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases, Alcoholic / drug therapy*
  • Liver Diseases, Alcoholic / metabolism
  • Liver Diseases, Alcoholic / prevention & control*
  • Male
  • Mice, Inbred C57BL
  • PPAR alpha / metabolism*
  • Phytotherapy
  • Protective Agents / administration & dosage
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use
  • Salvia miltiorrhiza
  • Triglycerides / metabolism

Substances

  • Aldehydes
  • Drugs, Chinese Herbal
  • PPAR alpha
  • Protective Agents
  • Triglycerides
  • dan-shen root extract
  • Ethanol
  • 4-hydroxy-2-nonenal

Grants and funding

This work was supported by the Natural Science Foundation of China [grant numbers 81473393 to XD, 81470845 to ZS], http://www.nsfc.gov.cn/; and the National Science Fund for Distinguished Young Scholars [grant number LR15H030003 to XD], http://www.nsfc.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.