Objective To observe the effect of water extract of Crataegus pinnatifida leaves on vascular inflammatory injury and systemic lipid metabolism disorders in apolipoprotein E knockout (ApoE^−/−) mice induced by homocysteine (Hcy) and high fat. Methods Eight C57BL/6J mice fed a normal diet were served as the control group, 40 ApoE^−/− mice were randomly divided into high-fat group, high-fat + methionine group, simvastatin (5.7 mg/kg) group, C. pinnatifida leaves low-and high-dose (12, 24 g/kg) groups, with eight mice in each group. Except for the control group, all other mice were fed a 21% high-fat diet for 18 weeks. Starting from the 11th week, except for the control and high-fat groups, the remaining mice were received daily intragastric administration of methionine (1 g/kg) to induce hyperhomocysteinemia. Corresponding drugs were administered to each treatment group, while the control and high-fat groups received an equivalent volume of saline. Counts of white blood cells, red blood cells, hemoglobin and platelets in peripheral blood were measured. Levels of Hcy, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr) and blood urea nitrogen (BUN) in serum were assessed. Oil red O staining was used to observe lipid plaques in aortic intima and lipid content in liver sections. Filipin staining was used to measure hepatic cholesterol level. Hematoxylin-eosin (HE) staining was used to examine pathological morphological changes in aortic tissue. Masson staining was used to detecte collagen fiber deposition in aorta. Immunofluorescence staining was used to evaluate the expressions of p50, p65 in aorta and sterol regulatory element binding protein 1 (SREBP1) and SREBP2 in liver. Results Compared with control group, levels of Hcy, TC, TG, LDL-C and inflammatory factors in serum of mice in high-fat group and high-fat + methionine group were significantly increased (P < 0.01), while the level of HDL-C was significantly decreased (P < 0.01). The red stained area of aorta was significantly increased (P < 0.01), the endometrium was thickened and showed obvious pathological changes, lipid accumulation was increased (P < 0.01), and expressions of p50, p65 were increased (P < 0.01). The expressions of SREBP1 and SREBP2 in liver were increased (P < 0.01), and the lipid content was increased (P < 0.01). Compared with high-fat + methionine group, levels of Hcy, TC, TG, LDL-C and inflammatory factors in serum of mice in each treatment group were significantly reduced (P < 0.01), while the level of HDL-C was significantly increased (P < 0.05, 0.01). The red stained area of aorta was significantly reduced (P < 0.01), pathological changes were alleviated, lipid accumulation was reduced (P < 0.01), and the expressions of p50, p65 were reduced (P < 0.01). The expressions of SREBP1 and SREBP2 in liver were decreased (P < 0.01), and the lipid content was decreased (P < 0.01). Conclusion The water extract of C. pinnatifida leaves could improve the atherosclerosis of blood vessels in mice, and its mechanism may be closely related to the inhibition of inflammatory damage of vascular endothelium and liver lipid synthesis.

Crataegus pinnatifida leaves  /  homocysteine  /  high fat  /  ApoE^-/- mice  /  atherosclerosis  /  nuclear factor-κB  /  sterol regulatory element binding protein  /  vitexin-2-O-rhamnoside  /  hyperoside