Protective Effect of Panax Notoginseng Saponins on Apolipoprotein-E-deficient Atherosclerosis-prone Mice

Abstract

Background: It is widely recognized that atherosclerosis (AS) is related to vascular inflammation. Panax notoginseng saponins (PNS) extracted from the roots of Panax notoginseng have been shown to possess anti-inflammatory activity. It is widely used in the clinical treatment of cardiovascular and cerebrovascular diseases, but the protective effect of PNS on atherosclerosis is not fully understood. This study was designed to test the effects of PNS administration in apolipoprotein (apo)-E-deficient (ApoE-/-) mice on the activation of NF-κB p65, IL-1β, IL-6, TNF-α and Calpain1 proteins.

Methods: 24 ApoE-/- mice fed with high-fat diet for 8 weeks to create the AS model. PNS, dissolved in three distilled water, was administered orally to two treatment groups at dosages of 60 mg/kg/d/mice and 180 mg/kg/d/mice. After 8 weeks, peripheral blood was collected for assessing the levels of TG, TC, LDL-C and HDL-C in serum by Biochemical Analyzer. HE staining was used to observe pathomorphological changes in the aortic root. Oil Red O staining was used to observe the lipid deposition in the aortic root. ELISA kits were used to assess the levels of IL-1β and TNF-α in serum. The expression levels of NF-κB p65, IL-1β, IL-6, TNF-α, and Calpain1 proteins in the aortic root were identified by Western blot.

Results: After PNS administration for 8 weeks, the levels of TG, TC, LDL-C, IL-1β and TNF-α were decreased, the level of HDL-C was increased in apoE-/- mice. The arrangement of the tissue of aortic root tended to be normal, the cell morphology was restored, and the lipid depositions were reduced in apoE-/- mice treated with PNS. Moreover, PNS inhibited the expression levels of NF-κB p65, IL-6, IL-1β, TNF-α and Calpain1 proteins of aortic root tissues in apoE-/- mice.

Conclusion: PNS may inhibit the progression of atherosclerotic lesions via their anti-inflammatory biological property. PNS suppress the NF-κB signaling pathway and inhibits the expression of pro-inflammatory factors such as NF-κB p65, IL-6, IL-1β, TNF-α and Calpain1 proteins in aortic root tissues of apoE-/- mice.

Keywords: Apolipoprotein(apo)-E-deficient mice; Atherosclerosis; Inflammatory cytokines; Nuclear factor kappa B; Panax notoginseng saponins; dyslipidaemia.