Animal studies and AI-based analysis identify the efficacy of berberine to inhibit experimental abdominal aortic aneurysms.

Background: Currently, no drug treatment is available for abdominal aortic aneurysms (AAAs). Berberine, an alkaloid extracted from the traditional Chinese herbs Coptis chinensis and Phellodendron amurense, has several beneficial biological effects, including anti-inflammatory properties.

Purpose: The aim of this study was to explore whether berberine affects the pathogenesis of AAAs.

Methods: An intraluminal porcine pancreatic elastase (PPE) infusion-induced mouse model of AAAs and AI-based analysis were used to identify the efficacy of berberine in the inhibition of experimental AAAs.

Results: We found that berberine treatment significantly inhibited PPE-induced aortic dilation. Histopathologic analysis revealed that berberine treatment reduced PPE-induced inflammatory cell infiltration in the aortic wall, promoted vascular smooth muscle cell (VSMC) survival, and protected against medial elastin degradation. Moreover, berberine treatment also downregulated matrix metalloproteinase 2 (MMP-2) and MMP-9 expression in the aortic wall and reduced abnormal mural angiogenesis. Through the use of public databases and bioinformatics, machine learning, and molecular docking techniques, RUNX2, VCAM-1, and CCL2 were identified as hub genes through which berberine inhibits AAAs. To confirm the above results, we performed tissue-specific knockout of Runx2 in VSMCs and found that Runx2 deficiency attenuated PPE-induced AAAs by increasing medial smooth muscle cell depletion, elastin degradation, and aortic inflammation.

Conclusion: In conclusion, berberine has an anti-aneurysmal effect, which may be related to the protection of VSMCs and elastin related to positive vascular remodeling and the inhibition of abnormal aortic inflammation. This study is the first to demonstrate the anti-aneurysmal effect of berberine, which may provide a new potential option for treating AAAs.