Paeoniflorin Ameliorates Atherosclerosis by Suppressing TLR4-Mediated NF-κB Activation

Paeoniflorin, a type of bioactive monoterpene glucoside in Paeoniae Radix, possesses anti-oxidative, anti-inflammatory and anti-hyperglycaemic properties. However, the underlying mechanism of paeoniflorin in treating atherosclerosis is unclear. A rat model of high-fat diet-induced atherosclerosis and palmitic acid (PA)-treated vascular smooth muscle cells (VSMCs) were used in this study. The serum concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were determined, and the results indicated that paeoniflorin remarkably lowered the levels of TC, TG and LDL-C induced by a high-fat diet. Histopathological results showed that paeoniflorin significantly improved the pathological changes in the aorta. In addition, paeoniflorin also maintained a normal weight gain speed. Subsequently, the effects of paeoniflorin on the production of inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) were detected by qPCR and ELISA. The qPCR and ELISA results showed that paeoniflorin decreased the levels of these inflammatory cytokines. Moreover, the expression of TLR4 and its downstream pathway molecules was measured by Western blot. The results indicated that paeoniflorin significantly reduced the expression of TLR4 and MyD88 as well as the phosphorylation of I kappa B alpha and NF-kappa B p65. Taken together, these results suggested that paeoniflorin could alleviate atherosclerotic inflammation by inhibiting the TLR4/MyD88/NF-kappa B pathway. Therefore, paeoniflorin may be a potential therapy for atherosclerosis.