A Biomedical Investigation of the Hepatoprotective Effect of Radix salviae miltiorrhizae and Network Pharmacology-Based Prediction of the Active Compounds and Molecular Targets

Int J Mol Sci. 2017 Mar 13;18(3):620. doi: 10.3390/ijms18030620.

Abstract

Radix salviae miltiorrhizae (Danshen in Chinese), a classic traditional Chinese medicine (TCM) herb, has been used for centuries to treat liver diseases. In this study, the preventive and curative potential of Danshen aqueous extract on acute/chronic alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) was studied. The in vivo results indicated that Danshen could alleviate hepatic inflammation, fatty degeneration, and haptic fibrogenesis in ALD and NAFLD models. In the aspect of mechanism of action, the significant reduction in MDA levels in both ALD and NAFLD models implies the decreased levels of oxidative stress by Danshen. However, Danshen treatment could not activate the internal enzymatic antioxidant system in ALD and NAFLD models. To further explore the hepatoprotective mechanism of Danshen, an in silico-based network pharmacology approach was employed in the present study. The pharmacological network analysis result revealed that six potential active ingredients such as tanshinone iia, salvianolic acid b, and Danshensu may contribute to the hepatoprotective effects of Danshen on ALD and NAFLD. The action mechanism may relate with regulating the intracellular molecular targets such as PPARα, CYP1A2, and MMP2 for regulation of lipid metabolism, antioxidant and anti-fibrogenesis by these potential active ingredients. Our studies suggest that the combination of network pharmacology strategy with in vivo experimental study may provide a forceful tool for exploring the mechanism of action of traditional Chinese medicine (TCM) herb and developing novel bioactive ingredients.

Keywords: Radix salviae miltiorrhizae; antioxidant; hepatoprotective; network pharmacology.

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Biomarkers
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Computational Biology / methods
  • Drugs, Chinese Herbal / chemistry*
  • Drugs, Chinese Herbal / pharmacology*
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Liver Function Tests
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Oxidative Stress / drug effects
  • Protective Agents / chemistry*
  • Protective Agents / pharmacology*
  • Salvia miltiorrhiza / chemistry*

Substances

  • Antioxidants
  • Biomarkers
  • Drugs, Chinese Herbal
  • Protective Agents