Effects and mechanisms of Danshen-Shanzha herb-pair for atherosclerosis treatment using network pharmacology and experimental pharmacology

J Ethnopharmacol. 2019 Jan 30:229:104-114. doi: 10.1016/j.jep.2018.10.004. Epub 2018 Oct 9.

Abstract

Ethnopharmacological relevance: The danshen (the root of Salvia miltiorrhiza Bge.)-shanzha (the fruit of Crataegus pinnatifida Bge. var. major N.E.Br.) (DS) herb combination is a commonly used traditional Chinese medicine with cardiovascular disease (CVD) treatment potential.

Materials and methods: In this study, we investigated the anti-atherosclerotic effects and mechanisms of DS by the integration of network pharmacology and polypharmacology. Eight main components were selected for target fishing by PharmMapper.

Results: The network pharmacological study indicated that DS may target 41 proteins and 16 pathways associated with inflammation, lipid metabolism and endothelial protection, which indicates that DS probably adjusts these processes as part of its anti-atherosclerotic activities. Furthermore, this hypothesis was verified by polypharmacology using an atherosclerotic model. Histopathological examination showed that DS inhibited pathological changes in the arteries of atherosclerotic rats and reduced the intima-media thickness (IMT). DS significantly reduced the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) and increased the high-density lipoprotein-cholesterol (HDL-C) level in the blood. DS also decreased the concentrations of interleukin (IL)-1β and IL-18, indicating anti-inflammation activity. In addition, DS increased the serum levels of nitric oxide (NO) and 6-keto-prostaglandin F (6-keto-PGF) and decreased the serum levels of endothelin (ET) and thromboxane B2 (TXB2), indicating an endothelial protective effect.

Conclusions: In conclusion, DS has an anti-atherosclerotic ability to lower lipid concentrations and to protect endothelial function, and it also has anti-inflammatory activity.

Keywords: Atherosclerosis; Experimental pharmacology; Fruit of Crataegus pinnatifida Bge var. major N.E.Br.; Network pharmacology; Root of Salvia miltiorrhiza Bge.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Aorta / drug effects
  • Aorta / pathology
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / pathology
  • Carotid Intima-Media Thickness
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Lipids / blood
  • Male
  • Rats, Wistar
  • Salvia miltiorrhiza

Substances

  • Anti-Inflammatory Agents
  • Drugs, Chinese Herbal
  • Lipids
  • shanzha
  • dan-shen root extract