The Protective Effect of Crataegus aronia Against High-Fat Diet-Induced Vascular Inflammation in Rats Entails Inhibition of the NLRP-3 Inflammasome Pathway

Cardiovasc Toxicol. 2020 Feb;20(1):82-99. doi: 10.1007/s12012-019-09534-9.

Abstract

This study investigated whether the whole-plant aqueous extract of Crataegus aronia (C. aronia) could protect against or alleviate high-fat diet (HFD)-induced aortic vascular inflammation in rats by inhibiting the NLRP-3 inflammasome pathway and examined some mechanisms of action with respect to its antioxidant and hypolipidemic effects. Adult male Wistar rats were divided into five groups (n = 6/each): standard diet (10% fat) fed to control rats, control + C. aronia (200 mg/kg), HFD (40% fat), HFD + C. aronia, and HFD post-treated with C. aronia. The HFD was fed for 8 weeks and C. aronia was administered orally for 4 weeks. In addition, isolated macrophages from control rats were pre-incubated with two doses of C. aronia (25 and 50 μg/mL) with or without lipopolysaccharide (LPS) stimulation. Only in HFD-fed rats, co- and post-C. aronia therapy lowered circulatory levels of LDL-C and ox-LDL-c and aortic protein levels of LOX-1 and CD36. C. aronia also inhibited the nuclear accumulation of NF-κB and lowered protein levels of NLRP-3, caspase-1, and mature IL-1β. In vitro, in the absence of ox-LDL-c, C. aronia led to reduced nuclear levels of NF-κB, ROS generation, and protein NLRP-3 levels, in both LPS-stimulated and unstimulated macrophages, in a dose-dependent manner. However, protein levels of LOX-1 were not affected by C. aronia in unstimulated cells. In conclusion, C. aronia inhibits the NLRP-3 inflammasome pathway, induced by HFD feeding in the aorta of rats, mainly by its hypolipidemic effect and in vitro, in LPS-stimulated macrophages, by its antioxidant effect.

Keywords: C. aronia; NLRP-3 inflammasome; Vascular inflammation; ox-LDL-c.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Aorta / drug effects*
  • Aorta / immunology
  • Aorta / metabolism
  • Aorta / pathology
  • Aortitis / etiology
  • Aortitis / immunology
  • Aortitis / metabolism
  • Aortitis / prevention & control*
  • Atherosclerosis / etiology
  • Atherosclerosis / immunology
  • Atherosclerosis / metabolism
  • Atherosclerosis / prevention & control*
  • Cells, Cultured
  • Crataegus
  • Diet, High-Fat
  • Disease Models, Animal
  • Hypolipidemic Agents / isolation & purification
  • Hypolipidemic Agents / pharmacology*
  • Inflammasomes / antagonists & inhibitors*
  • Inflammasomes / immunology
  • Inflammasomes / metabolism
  • Inflammation Mediators / metabolism
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Oxidative Stress / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Hypolipidemic Agents
  • Inflammasomes
  • Inflammation Mediators
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Plant Extracts
  • Reactive Oxygen Species
  • crataegus extract