Berberine inhibited carotid atherosclerosis through PI3K/AKTmTOR signaling pathway

Bioengineered. 2021 Dec;12(1):8135-8146. doi: 10.1080/21655979.2021.1987130.

Abstract

Atherosclerosis, a multifactorial vascular disease resulting from lipid metabolism disorders, features chronic inflammatory damage resulting from endothelial dysfunction, which usually affects multiple arteries. The carotid artery is a common site for clinical atherosclerosis evaluation. The aortic root is the standard site for quantifying atherosclerosis in mice. Due to the adverse reactions of first-line drugs, it is necessary to discover new drugs to prevent and treat atherosclerosis. Berberine (BBR) is one of the most promising natural products derived from herbal medicine Coptidis Rhizoma (Huanglian) that features significant anti-atherosclerosis properties. However, overall BBR mechanism against carotid atherosclerosis has not been clearly discovered. Our work aimed to investigate potential BBR mechanism in improving carotid atherosclerosis in ApoE knockout mice. Here, we proved that in ApoE -/- mice receiving high-fat diet for 12 weeks, BBR can reduce serum lipid levels, improve intimal hyperplasia, and antagonize carotid lipid accumulation, which may be achieved through regulating the PI3K/AKT/mTOR signaling pathway, regulating autophagy, promoting cell proliferation and inhibiting cell apoptosis. In summary, these data indicate that BBR can ameliorate carotid atherosclerosis. Therefore, it could be a promisingly therapeutic alternative for atherosclerosis.

Keywords: Carotid atherosclerosis; berberine; endothelial dysfunction; signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Berberine / administration & dosage*
  • Berberine / pharmacology
  • Carotid Artery Diseases / chemically induced
  • Carotid Artery Diseases / drug therapy*
  • Carotid Artery Diseases / genetics
  • Carotid Artery Diseases / metabolism
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Lipids / blood
  • Male
  • Mice
  • Mice, Knockout, ApoE
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Lipids
  • Berberine
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases

Grants and funding

This work was supported by the Jinan Science and Technology Development Plan Project (NO. 202019151) and the Special Technical Project of TCM’s Prevention and Treatment of “ Carotid Atherosclerostic Plaque” Based on Heart Governing Blood and Vessels Theory (Luweihan [2021] No. 45).