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

  • Abdullah S. ShatoorEmail author
  • Suliman Al Humayed
Article

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.

Graphic Abstract

Keywords

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

Abbreviations

CARD

Caspase recruitment domain

C. aronia

Crataegus aronia

CHOL

Cholesterol

HDL-c

High-density lipoprotein cholesterol

ECs

Endothelial cells

HFD

High-fat diet

IL-6

Interleukin-6

IL-1β

Interleukin 1β

IκBα

Inhibitory factor kappa B-α subunit

IKK

IκB kinase

LDL-c

Low-density lipoprotein cholesterol

LPS

Lipopolysaccharide

LOX-1

Oxidized LDL receptor

MDA

Malondialdehyde

NF-kB

Nuclear factor kappa B

ox-LDL-c

Oxidized low-density lipoprotein cholesterol

ROS

Reactive oxygen species

STD

Standard diet

TNF-α

Tumor necrosis factor-α

VSMs

Vascular smooth muscles

Notes

Acknowledgements

The authors would like to express their sincere gratitude to the staff of the department of pharmacognosy at the college of pharmacy King Khalid University (KKU), Abha, Kingdom of Saudi Arabia, for their contribution to the current work. They also would like to thank the physiology and the biochemistry form the College of Medicine at KKU for their help in the biochemical analysis of this study.

Funding

This work was supported by the deanship of scientific research at King Khalid University, Abha, Kingdom of Saudi Arabia for fully funding this project [Grant no. R.G.P.1/41/39].

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. 1.Department of Medicine, Cardiology Section, College of MedicineKing Khalid UniversityAbhaSaudi Arabia
  2. 2.Department of Medicine, College of MedicineKing Khalid UniversityAbhaSaudi Arabia

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