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

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.