Chikusetsusaponin IV protects against atherosclerosis by downregulating the NF-κB/ COX-2 and PI3K/AKT/mTOR signaling pathway

Abstract

Objective: To investigate the anti-atherosclerosis effect of chikusetsusaponin IV (CSIV) against high-fat diet-induced atherosclerosis in rats.

Methods: A high-fat diet was used for the induction of atherosclerosis in rats, and the rats received oral CSV or atorvastatin. The body weight, organ weights, food intake, calorie intake, lipid parameters, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)/mevalonate ratio, collagen, free fatty acid, cardiac parameters, apolipoprotein (A and B), antioxidant parameters, inflammatory cytokines, and inflammatory parameters were assessed. The mRNA expressions of interleukin-1β (IL-β), tumor necrosis factor-α (TNF-α), IL-6, IL-17, PI3K, AKT, and mTOR were estimated.

Results: CSV significantly modulated food intake, body weight, organ weight (liver, kidney, and heart), and calories (P<0.05). Total cholesterol, triglycerides, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, cardiovascular risk index-1, and cardiovascular risk index-2 were decreased, while high-density lipoprotein cholesterol and anti-atherogenic index were increased significantly in the CSV group (P<0.05). Besides, CSV significantly restored the level of HMG-CoA/mevalonate ratio, collagen, free fatty acid, cardiac parameters (creatinine kinase-MB, lactate dehydrogenase, cTnT, cTnI), apolipoprotein (apolipoprotein A and apolipoprotein B), antioxidant parameters (MDA, CAT, GPx, GSH, SOD), inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10), inflammatory parameters (COX-2, TGF-β, NF-κB), intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1. CSV also decreased the mRNA expression of IL-1β, TNF-α, IL-6, IL-17, PI3K, AKT, and mTOR.

Conclusions: This study showed the anti-atherosclerosis effect of CSV against high-fat diet-induced atherosclerosis in rats via alteration of NF-κB/COX-2 and PI3K/AKT/mTOR signaling pathway.

Keywords

Atherosclerosis / Chikusetsusaponin IV / Inflammation / Oxidative stress / PI3K/AKT/mTOR signaling pathway

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

The current research study was funded by the Yancheng Municipal Health Commission 2024 Medical Research Project (YK2024166).

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

BW performed the experimental study. GSM designed the experimental study. Both authors drafted and proofread the manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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