Vasicine attenuates atherosclerosis via lipid regulation, inflammation inhibition, and autophagy activation in ApoE-/- mice

Int Immunopharmacol. 2024 Dec 5;142(Pt A):112996. doi: 10.1016/j.intimp.2024.112996. Epub 2024 Sep 6.

Abstract

Atherosclerosis is marked with the accumulation of low-density lipoproteins and chronic inflammation. The anti-inflammatory therapies exert protective effects on atherosclerosis. Vasicine is a bioactive alkaloid with anti-inflammatory activity from a medicinal plant in Ayurveda and Unani. In this study, the effects of vasicine were evaluated on atherosclerosis in vivo and in vitro. The results showed that vasicine alleviated atherosclerotic lesions and regulated the lipid synthesis by reducing the levels of TC, TG, LDL-C and inhibiting the expresses of scavenger receptors (SR-A, CD36 and LOX-1) to inhibit foam cell formations. And vasicine decreased the levels of IL-1β, IL-6, MCP-1, and TNF-α to modulate inflammatory response. Besides, vasicine downregulated MAPK and PI3K/AKT/mTOR pathway to activated autophagy, which inhibited the procession of atherosclerosis.

Keywords: Apolipoprotein-E-deficient mice; Atherosclerosis; Autophagy; Inflammation; Vasicine.

MeSH terms

  • Alkaloids / pharmacology
  • Alkaloids / therapeutic use
  • Animals
  • Anti-Inflammatory Agents* / pharmacology
  • Anti-Inflammatory Agents* / therapeutic use
  • Apolipoproteins E / genetics
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / metabolism
  • Autophagy* / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Foam Cells / drug effects
  • Foam Cells / metabolism
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Lipid Metabolism / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RAW 264.7 Cells
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Apolipoproteins E
  • Cytokines
  • Alkaloids