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

• Published in: PloS one 2017-10, Vol.12 (10), p.e0186357
• Main Authors: Ding, Lei, Wo, Like, Du, Zhongyan, Tang, Lihua, Song, Zhenyuan, Dou, Xiaobing
• Format: Article
• Language: English
• Subjects: 4-Hydroxynonenal; Activation; Alcohol; Alcohol use; Alcoholism - drug therapy; Alcoholism - metabolism; Alcoholism - pathology; Alcohols; Aldehydes - metabolism; Animals; Apoptosis; Biology and Life Sciences; Cell culture; Cell death; Cell Death - drug effects; Chinese medicine; Degradation; Dietary Supplements; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Ethanol; Ethanol - administration & dosage; Fatty acids; Hep G2 Cells; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatocytes - pathology; Herbal medicine; Humans; Life sciences; Lipids; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver diseases; Liver Diseases, Alcoholic - drug therapy; Liver Diseases, Alcoholic - metabolism; Liver Diseases, Alcoholic - prevention & control; Male; Medical treatment; Medicine and Health Sciences; Metabolic disorders; Metabolites; Mice, Inbred C57BL; Molecular modelling; Oxidative stress; Phytotherapy; PPAR alpha - metabolism; Protective Agents - administration & dosage; Protective Agents - pharmacology; Protective Agents - therapeutic use; Research and Analysis Methods; Rodents; Salvia miltiorrhiza; Supplements; Toxicology; Traditional Chinese medicine; Triglycerides - metabolism; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0186357

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.