Frog skin antimicrobial peptide chensinin-1b and its analogs suppresses inflammatory response by regulating the canonical Wnt/β-catenin pathway in oxidative low-density lipoprotein induced atherosclerosis

The deposition of lipid components and inflammatory substances in the arterial vessel walls is the main cause of the development of atherosclerosis. Although there is currently a lack of effective treatment methods, reducing the release of pro-inflammatory factors and alleviating the abnormal accumulation of cholesterol remain one of the main therapeutic strategies for atherosclerosis. Chensinin-1b, a derivative of the natural antimicrobial peptide extracted from the skin secretions of the Rana chensinensis , has been shown to effectively mitigate the occurrence of inflammatory responses. The primary aim of this study is to investigate the regulatory effect of the canonical Wnt signaling pathway on atherosclerosis and elucidate the anti-atherosclerotic mechanism of antimicrobial peptides by Wnt/β-catenin signaling. This study found that ox-LDL upregulated the expression of Wnt1, β-catenin and the downstream target protein cyclin D1 and c-myc, indicating the activation of the canonical Wnt signaling pathway in foaming THP-1 cells. IWP-2 reduced the release of proinflammatory cytokines and the intracellular total cholesterol and free cholesterol level by inhibiting Wnt/β-catenin signaling. Chensinin-1b and its analogs downregulated the expression of Wnt signaling proteins, meanwhile reduced the release of proinflammatory cytokines and the intracellular total and free cholesterol level. Overall, our study suggested that the canonical Wnt signaling pathway was activated in ox-LDL-induced foaming macrophage. Chensinin-1b and its analogs alleviated ox-LDL induced lipid accumulation and inflammation through the inhibition of canonical Wnt signaling, suggesting a potential AS therapeutic agent of AMP.