Yin-xing-tong-mai decoction attenuates atherosclerosis via activating PPARγ-LXRα-ABCA1/ABCG1 pathway

Pharmacol Res. 2021 Jul:169:105639. doi: 10.1016/j.phrs.2021.105639. Epub 2021 Apr 28.

Abstract

Atherosclerosis is now the major cause of mortality and morbidity worldwide. Formation of macrophage-derived foam cells is a hallmark of atherosclerosis, which is regulated by cholesterol uptake, intracellular metabolism, and efflux. PPARγ-LXRα-ABCA1/ABCG1 pathway plays an important part in regulating cholesterol efflux and this pathway could be a promising target for treating atherosclerosis. However, due to undesirable systemic effects, PPARγ agonist therapy for atherosclerosis remains challenging. Many traditional Chinese medicine has been well accepted and applied in atherosclerosis treatment. Yin-xing-tong-mai decoction (YXTMD) has been applied for treating atherosclerosis for decades. However, the mechanism remains to be explored. Here, we showed that YXTMD effectively attenuated atherosclerosis in ApoE-/- mice. YXTMD increased cholesterol efflux of foam cell by upregulation of ABCA1 and ABCG1 in vivo and in vitro. Through bioinformatic analysis and experimental validation, we found that PPARγ was an important downstream effector of YXTMD in macrophages. Reduction of PPARγ significantly decreased LXRα, ABCA1, and ABCG1 expression in macrophages, with reduced cholesterol efflux. In conclusion, these findings confirmed that YXTMD attenuated atherosclerosis by activating the PPARγ-LXRα- ABCA1/ABCG1 pathway to enhance cholesterol efflux.

Keywords: (-)- catechin (PubChem CID: 73160); Atherosclerosis; Cholesterol efflux; Foam cell; PPARγ; Yin-xing-tong-mai decoction; chlorgenic acid (PubChem CID: 1794427); genistein (PubChem CID: 5280961).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism*
  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / metabolism*
  • Animals
  • Atherosclerosis / drug therapy*
  • Cholesterol / metabolism
  • Disease Models, Animal
  • Drugs, Chinese Herbal / therapeutic use*
  • Liver X Receptors / metabolism*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma / metabolism*
  • Signal Transduction / drug effects*

Substances

  • ABCA1 protein, mouse
  • ABCG1 protein, mouse
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • Drugs, Chinese Herbal
  • Liver X Receptors
  • PPAR gamma
  • Cholesterol