Berberine ameliorates atherosclerosis by inhibiting the phenotypic transition of vascular smooth muscle cells via suppression of the JAK2/STAT3 signaling pathway

Atherosclerosis (AS) is a widespread cardiovascular disease that significantly impacts human health. This study aimed to investigate the anti-atherosclerotic effects of berberine (BBR) and elucidate its mechanisms through animal and cellular experiments. Apolipoprotein E-deficient (ApoE^-/-) mice were fed a high-fat diet for 12 weeks to induce AS. The mice were subjected to the corresponding interventions for 4 weeks. After the intervention, aortic pulse wave velocity (PWV) was analyzed by UBM imaging. Blood samples were collected to analyze serum lipid levels. Immunofluorescence was used to detect the phenotypic conversion of vascular smooth muscle cells (VSMCs) in the vessel wall. Transcript levels of relevant proteins in the tissues were examined by real-time quantitative polymerase chain reaction (RT-qPCR). In vitro, rat aortic VSMCs (A7r5) were treated with oxidized low-density lipoprotein (ox-LDL) to establish a disease model. The cell proliferation and migration abilities, as well as the expression levels of alpha-smooth muscle actin (α-SMA), osteopontin (OPN), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) were all examined. Our research results indicate that BBR may delay the occurrence and development of AS by down-regulating the JAK2/STAT3 signaling pathway and inhibiting the phenotypic transformation of VSMCs. Activation of STAT3 can weaken the beneficial effects of BBR. This suggests that BBR may be a promising candidate drug for treating patients with AS.