Abstract

Atherosclerosis is a significant cause of cardiovascular disease morbidity and mortality worldwide, seriously threatening human health and life. Therefore, the present study aimed to investigate the effects and mechanisms of Bufrudin in inhibiting atherosclerosis. The atherosclerosis model was induced using high-fat diet-fed apolipoprotein E knockout mice, which were fed a high-fat diet for 8 w and subsequently intraperitoneally injected with Bufrudin for 8 w; rosuvastatin was used as the positive group. Serum lipid levels, atherosclerotic lesion area and levels of related inflammatory factors were detected in mice, and the mechanism of the anti-atherosclerotic effect of Bufrudin was investigated by reverse transcription-quantitative polymerase chain reaction protein immunoblotting and immunohistochemistry. The results showed that similar to rosuvastatin, Bufrudin reduced serum cholesterol, low-density lipoprotein cholesterol and triglyceride levels, and increased high-density lipoprotein cholesterol levels in mice. Meanwhile, Bufrudin reduced the area of atherosclerotic lesions, increased the collagen content in atherosclerotic plaques and lowered the levels of interleukin-6, tumour necrosis factor-alpha and C-reactive protein in mice. In addition, Western blotting results showed that Bufrudin downregulated the expression of cellular myelocytomatosis oncogene, mitogen-activated protein kinase 3 and p38 proteins. Furthermore, reverse transcription-quantitative polymerase chain reaction and immunohistochemistry results showed that Bufrudin downregulated the expression of cluster of differentiation 36, tumour necrosis factor-alpha, toll-like receptor 4 and myeloid differentiation primary-response protein 88 messenger ribonucleic acid and proteins in mice. In conclusion, Bufrudin ameliorated atherosclerosis in apolipoprotein E knockout mice by mechanisms related to the improvement of serum lipid levels, inflammatory factor levels and with the inhibition of the toll-like receptor 4/nuclear factor kappa B and p38 mitogen-activated protein kinase pathways. The results revealed a novel anti-atherosclerosis mechanism of Bufrudin, which lays a foundation for its clinical use in modulating ather osclerosis.