Chlorogenic acid alleviates endothelial cell inflammation and apoptosis of Kawasaki disease.

PURPOSE: Kawasaki disease (KD) is an acute, self-limiting artery vasculitis, especially involving the coronary arteries. Chlorogenic acid (CGA) is a plant-derived polyphenolic compound with anti-inflammatory, anti-apoptotic, and anti-oxidative pharmacological effects. The purpose of this study was to explore the protective effects of CGA on KD and elucidate its mechanisms. METHODS: Candida albicans water-soluble fraction (CAWS) was used to establish a KD mouse model with coronary arteritis, and tumor necrosis factor α (TNF-α) was employed to induce human umbilical vein endothelial cell (HUVEC) injury of KD cell model, which was administrated in different ways and analyzed by hematoxylin–eosin (HE) staining, Masson trichrome staining, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, immunofluorescence staining, western blotting immunohistochemistry staining, real-time quantitative polymerase chain reaction (RT-qPCR), and so on. RESULTS: In vivo results showed that CGA could exert protective effects on KD mice through alleviating inflammation and fibrosis around the coronary arteries, and relieving vascular endothelial cell apoptosis. In vitro studies confirmed that CGA could inhibit TNF-α induced inflammation of HUVECs, similar to the NF-κB inhibitor QNZ. Additionally, it can also inhibit TNF-α induced HUVEC apoptosis by increasing BCL-2 expression as well as reducing TUNEL positive cells, the rates of flow cytometric apoptotic cells, and BAX expression. These effects could be reversed by the AMPK inhibitor compound c (CC). Further mechanistic study based on bioinformatics analysis and western blotting revealed that CGA could protect against vascular inflammation and cell apoptosis of KD through regulating the AMPK/mTOR/NF-κB pathway. CONCLUSION: CGA may have the potentially protective effects on KD through inhibition endothelial cell inflammation and apoptosis, suggesting that CGA may serve as an adjuvant for KD therapy in the future.