AUTHOR=Wu Huilan , Wang Yijia , Tan Pingping , Ran Yuqing , Guan Yuting , Qian Songwei , Feng Xing , Jiang Yalan , Peng Yongmiao , Sheng Ke , Xi Haitao , Ji Weiping , Guo Xiaoling 

TITLE=Ferulic acid suppresses the inflammation and apoptosis in Kawasaki disease through activating the AMPK/mTOR/NF-κB pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1420602

DOI=10.3389/fphar.2024.1420602

ISSN=1663-9812

ABSTRACT=Kawasaki disease (KD) is a self-limiting and acute systemic vasculitis of unknown etiology, mainly affecting children. Ferulic acid (FA), a natural phenolic substance, has multiple pharmacological properties, including anti-inflammatory, anti-apoptosis, and anti-fibrosis, and so on. The objective of this study was to investigate the protective effects of FA on KD, and try to elucidate the underlying mechanism. Based on the Candida albicans water soluble fraction (CAWS)-induced mouse coronary artery vasculitis of KD model, our in vivo results demonstrated that FA exerted anti-inflammatory effects on KD by inhibiting the infiltration of CD45-positive leukocytes and fibrosis around the coronary artery. Additionally, FA downregulated the levels of inflammatory and chemotactic cytokines, alleviated splenomegaly, and exhibited anti-apoptotic effects on KD by reducing TUNEL-positive cells, downregulating BAX expression, and upregulating BCL-2 expression. Based on the tumor necrosis factor α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury model, our in vitro findings showed that FA could effectively inhibit TNF-α-induced HUVEC inflammation like NF-κB inhibitor QNZ by downregulating the expression of pro-inflammatory cytokines as well as attenuated TNF-α-induced HUVEC apoptosis by reducing apoptotic cell numbers and the BAX/BCL-2 ratio, which could be reversed by the AMPK inhibitor compound c (CC).The further mechanistic study demonstrated that FA could restrain vascular endothelial cell inflammation and apoptosis in KD through activating the AMPK/mTOR/NF-κB pathway. However, FA alone is hard to completely restore KD into normal condition. In conclusion, FA has potential protective effects on KD, suggesting its promising role as an adjuvant for KD therapy in the future.