Zhang Jian, Zhuge Yingzhi, Rong Xing, Ni Chao, Niu Chao, Wen Zhengwang, Lin Hongzhou, Chu Maoping, Jia Chang
Pediatric Research Institute, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Children's Heart Center, Institute of Cardiovascular Development and Translational Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Cardiovasc Drugs Ther. 2023 Apr;37(2):257-270. doi: 10.1007/s10557-021-07277-w. Epub 2021 Oct 19.
Xijiao Dihuang Tang (XJDHT) is a classical formula of traditional Chinese medicine constituted of Cornu Bubali, Rehmannia glutinosa (Gaertn.) DC., Paeonia lactiflora Pall., and Paeonia suffruticosa Andrews. It was first mentioned in the medical classic "Beiji Qianjin Yaofang" written by Simiao Sun in Tang Dynasty. It shows very strong antipyretic and anticoagulant effects and has been clinically applied to treat various type of blood loss, purple and black spots, heat stroke, and glossitis. Kawasaki disease (KD) is considered as a kind of acute febrile illness in children with systemic vasculitis as the main lesions. The aim of this research is to clarify whether XJDHT can play a protective role in KD.
A mouse model of Candida albicans water-soluble fraction (CAWS)-induced coronary arteritis and a KD cell model with tumor necrosis factor (TNF)-α induction were employed to investigate the potential effect and mechanism of XJDHT on coronary artery injury in KD.
Data showed that XJDHT remarkably alleviated the coronary artery injury of KD mice, as evidenced by reduced inflammation and downregulated expression of pro-inflammatory cytokines interleukin (IL)-1β and TNF-α. In vitro investigation showed that XJDHT could promote cell proliferation, inhibit cell apoptosis, and improve mitochondrial functions. Subsequent studies demonstrated that XJDHT rescued endothelial cell injury by PI3K/Akt-NFκB signaling pathway. Component analysis of XJDHT detected thirty-eight chemically active ingredients, including paeoniflorin, albiflorin, and paeoniflorigenone, which in in vitro experiments exhibited significant rescue effects on TNF-α-mediated endothelial cell injury.
Our findings demonstrated that XJDHT mitigated coronary artery injury of KD through suppressing endothelial cell damage via PI3K/Akt-NFκB signaling.
犀角地黄汤是由水牛角、生地黄、芍药、牡丹皮组成的经典中药方剂。它最早在唐代孙思邈所著的医学典籍《备急千金要方》中被提及。该方显示出很强的解热和抗凝作用，临床上已被用于治疗各种类型的失血、紫癜、中暑和舌炎。川崎病（KD）被认为是一种以全身血管炎为主要病变的儿童急性发热性疾病。本研究的目的是阐明犀角地黄汤是否能对川崎病起到保护作用。
采用白色念珠菌水溶性成分（CAWS）诱导的小鼠冠状动脉炎模型和肿瘤坏死因子（TNF）-α诱导的川崎病细胞模型，研究犀角地黄汤对川崎病冠状动脉损伤的潜在作用及机制。
数据显示，犀角地黄汤显著减轻了川崎病小鼠的冠状动脉损伤，炎症减轻以及促炎细胞因子白细胞介素（IL）-1β和TNF-α的表达下调证明了这一点。体外研究表明，犀角地黄汤可促进细胞增殖、抑制细胞凋亡并改善线粒体功能。随后的研究表明，犀角地黄汤通过PI3K/Akt-NFκB信号通路挽救内皮细胞损伤。犀角地黄汤的成分分析检测到38种化学活性成分，包括芍药苷、 albiflorin和芍药苷元，在体外实验中，这些成分对TNF-α介导的内皮细胞损伤表现出显著的挽救作用。
我们的研究结果表明，犀角地黄汤通过PI3K/Akt-NFκB信号通路抑制内皮细胞损伤，从而减轻川崎病的冠状动脉损伤。
