Berberine prevents the formation of aortic dissection in C57BL/6 mice through the regulation of vascular smooth muscle cell function

Purpose Aortic dissection (AD) represents a critical medical condition characterized by a high mortality rate and limited therapeutic options. The pathogenesis of AD is associated with the extracellular matrix degradation, phenotypic switching and the loss of vascular smooth muscle cells (VSMCs). Berberine (BBR) has demonstrated promising protective effects in various cardiovascular diseases, but its impact on AD and the underlying mechanisms remains unexplored. This study aims to investigate the potential of BBR in reducing the development of AD and preventing the phenotypic transformation of VSMCs, thereby proposing a novel therapeutic strategy for this life-threatening condition. Methods C57BL/6J mice and isolated VSMCs were used as in vivo and in vitro models, respectively. An AD mouse model was established through intragastric administration of β-aminopropionitrile monofumarate (BAPN), and VSMC phenotypic transformation was induced by angiotensin II (Ang-II) to assess the preventative effects of BBR. Results BBR significantly mitigates AD in a BAPN-induced mouse model by reducing AD incidence from 80–45% and increasing survival rates from 50–70%. BBR treatment alleviates aortic dilation and improves aortic morphology, while also attenuating extracellular matrix degradation, as evidenced by reduced collagen type I and fibronectin degradation. Histological and immunohistochemical analyses reveal that BBR diminishes inflammation, as indicated by reduced IL-6 and HIF-1α expression, and mitigates oxidative stress by lowering MDA levels and enhancing SOD activity. Additionally, BBR counteracts VSMC phenotypic transformation and apoptosis, demonstrated by restored contractile protein levels and reduced caspase-3, AKT, and PI3K levels. It also inhibits VSMC proliferation, migration, and MMP expression in vitro , highlighting its protective role against AD progression. Conclusion BBR exhibits protective effects against BAPN-induced AD in C57BL/6J mice, highlighting its potential as a viable and innovative therapeutic option for preventing AD progression.