Apocynum Leaf Extract Suppresses the Progress of Atherosclerosis in Rats via the FKN/SYK/p38 Signal Pathway

To investigate the antiatherosclerotic effects of flavonoids extracted from Apocynum venetum (AVF) leaves in atherosclerotic rats and the underlying mechanisms, a total of 72 male Wistar rats were randomly divided into six groups: control group, model group, simvastatin group, low-dose AVF group, medium-dose AVF group, and high-dose AVF group. Atherosclerosis in rats was induced with a high-fat diet and an intraperitoneal injection of VD3 once daily for three contiguous days at a total injection dose of 70 U/kg. At the end of the 13th week, total serum cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) contents were measured. The hematoxylin-eosin (HE) staining was applied to evaluate the morphological changes. The ELISA method was used to detect related inflammatory factors and oxidative stress indicators. The corresponding protein expression and the mRNA level were detected by western blot analysis and reverse transcriptase PCR. HE staining showed that the thoracic aorta wall was thickened, and the aortic subendothelial foam cells and lipid vacuoles were reduced in the medium/high-AVF groups. Similarly, the TC, TG, LDL-C, and malondialdehyde (MDA) levels in the model group were significantly higher, but the HDL-C level and superoxide dismutase (SOD) activity were lower than those of the control group, and these effects were ameliorated by treatment with simvastatin or AVF. ELISA results showed that compared with the control group, the model group C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) results were significantly increased, and the medium AVF and high AVF could significantly reduce the expression of related inflammatory factors. The AVF inhibited intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin mRNA and related protein expression in the aorta in atherosclerotic rats. Western blot analysis also showed that AVF can significantly reduce the protein expression of fractalkine (FKN), spleen tyrosine kinase (SYK), and p38 mitogen-activated protein kinase (p38) in the rat aorta. We believe that the AVF can effectively reduce blood lipid levels in rats with atherosclerosis and delay atherosclerotic progression by inhibiting excessive inflammatory factors and inhibiting related adhesion factors. The underlying mechanism may be related to the FKN/SYK/p38 signaling pathway activity. Our results contribute to validating the traditional use of the Apocynum leaf extract in the treatment of atherosclerosis