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Protective Roles of Xijiao Dihuang Tang on Coronary Artery Injury in Kawasaki Disease

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

Our findings demonstrated that XJDHT mitigated coronary artery injury of KD through suppressing endothelial cell damage via PI3K/Akt-NFκB signaling.

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Availability of Data and Materials

The datasets obtained in the present study are available from the corresponding author on reasonable request.

Abbreviations

KD:

Kawasaki disease

XJDHT:

Xijiao Dihuang Tang

CAWS:

Candida albicans Water-soluble fraction

TNF-α:

Tumor necrosis factor-α

IL-1β:

Interleukin-1β

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Funding

This research was supported by Zhejiang Provincial Science and Technology Project of Traditional Chinese Medicine (No. 2018ZZ019), the Natural Science Foundation of China (No. 82000469, No. 81970435, No. 81770502, and No. 81900240), Zhejiang Provincial Natural Science Foundation of China (No. LY18H020012), Wenzhou Science & Technology Bureau Foundation (No. Y20190064), and Zhejiang Provincial Medicine and Health Technology Project (No. 2021KY801).

Author information

Author notes

  1. Jian Zhang, Yingzhi Zhuge, and Xing Rong contributed equally to this work.

Authors and Affiliations

  1. Pediatric Research Institute, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, China

    Jian Zhang, Yingzhi Zhuge, Chao Niu, Maoping Chu & Chang Jia

  2. 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

    Jian Zhang, Yingzhi Zhuge, Xing Rong, Chao Ni, Zhengwang Wen, Hongzhou Lin & Maoping Chu

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  1. Jian Zhang
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  2. Yingzhi Zhuge
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  3. Xing Rong
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  4. Chao Ni
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Contributions

ZJ, ZGYZ, and RX contributed equally to this paper and conducted the experiments, data acquisition, and manuscript writing. NC, NC, WZW, and LHZ performed partial animal experiments and data analysis. CMP and JC supervised all the experiments and revised the manuscript.

Corresponding authors

Correspondence to Maoping Chu or Chang Jia.

Ethics declarations

Ethics Approval and Consent to Participate

All the necessary experiments were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and the protocols were approved by the Animal Care and Use Committee of Wenzhou Medical University (wydw 2017–0046).

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Not applicable.

Research Involving Human Participants and/or Animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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The authors declare no competing interests.

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Zhang, J., Zhuge, Y., Rong, X. et al. Protective Roles of Xijiao Dihuang Tang on Coronary Artery Injury in Kawasaki Disease. Cardiovasc Drugs Ther 37, 257–270 (2023). https://doi.org/10.1007/s10557-021-07277-w

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  • DOI: https://doi.org/10.1007/s10557-021-07277-w

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