Sodium Danshensu stabilizes atherosclerotic vulnerable plaques by targeting IKKβ mediated inflammation in macrophages
Miao Zeng, Xiaolu Zhang, Nuan Lv, Luming Wang, Yanrong Suo, Jiali Gan, Lin Yang, Bin Yu, Xijuan Jiang, Wenyun Zeng
Abstract
BACKGROUND: The primary cause of acute cardiovascular events with high mortality is the rupture of atherosclerotic plaque followed by thrombosis. Sodium Danshensu (SDSS) has shown potential in inhibiting the inflammatory response in macrophages and preventing early plaque formation in atherosclerotic mice. However, the specific targets and detailed mechanism of action of SDSS are still unclear. OBJECTIVE: This study aims to investigate the efficacy and mechanism of SDSS in inhibiting inflammation in macrophages and stabilizing vulnerable plaques in atherosclerosis (AS). MATERIALS AND METHODS: mice. Subsequently, IKKβ was identified as a potential target of SDSS through protein microarray, network pharmacology analysis, and molecular docking. Additionally, ELISA, RT-qPCR, Western blotting, and immunofluorescence were employed to measure the levels of inflammatory cytokines, IKKβ, and NF-κB pathway-related targets, thereby confirming the mechanism of SDSS in treating AS both in vivo and in vitro. Finally, the impact of SDSS was observed in the presence of an IKKβ-specific inhibitor. RESULTS: mice. Furthermore, it was identified that IKKβ serves as the primary binding target of SDSS. Additionally, both in vivo and in vitro experiments demonstrated that SDSS effectively inhibits the NF-κB pathway by targeting IKKβ. Lastly, the combined use of the IKKβ-specific inhibitor IMD-0354 further enhanced the beneficial effects of SDSS. CONCLUSIONS: SDSS stabilized vulnerable plaques and suppressed inflammatory responses by inhibiting the NF-κB pathway through its targeting of IKKβ.