Liquiritigenin attenuates aneurysm progression and local inflammatory activation in a rabbit common carotid artery aneurysm model

Abstract

Intracranial aneurysms (IAs) are life-threatening vascular lesions closely associated with chronic inflammation in the local microenvironment. This study investigated the regulatory effect of liquiritigenin (LG), a natural flavonoid with anti-inflammatory properties, on aneurysm-associated inflammatory and vascular remodeling responses, with emphasis on HMGB1-related inflammatory signaling. Using a rabbit common carotid artery aneurysm model, we assessed the impact of liquiritigenin on inflammatory markers through histology, immunofluorescence, qPCR, and Western blot analysis. The results showed that aneurysm formation was accompanied by enhanced local inflammatory activation and increased expression of inflammation- and angiogenesis-related markers, including HMGB1, TLR4, IL-6, TREM1, TNF-α, and VEGF. Liquiritigenin treatment reduced aneurysm diameter, alleviated vessel wall pathology, and attenuated the local expression of several inflammatory and angiogenic markers. Furthermore, spatial analysis revealed heterogeneous inflammatory responses within the aneurysmal wall, suggesting the presence of localized inflammatory hotspots. In conclusion, liquiritigenin attenuates aneurysm progression in a rabbit carotid artery aneurysm model, at least in part, by modulating the local inflammatory microenvironment. These findings support liquiritigenin as a potential adjunctive pharmacological candidate for stabilizing aneurysmal vascular lesions by targeting inflammatory dysregulation.