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Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 3: 473 - 484

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.03.006

Matrine alleviates coronary microvascular dysfunction in ischemia with non-obstructive coronary artery disease mice induced by advanced glycation end products via inhibition of the reactive oxygen species-mediated endoplasmic reticulum stress in cardiac microvascular endothelial cells

  • Haixia DU ,
  • Chuan QIU ,
  • Yanpeng MA ,
  • Shuo PAN ,
  • Xiqiang WANG ,
  • Junkui WANG ,
  • Zhongwei LIU
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  • 1 Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an 710068, China; Department 403, PLA Rocket Force University of Engineering, Xi’an 710025, China
    2 Division of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane Center of Biomedical Informatics and Genomics, Tulane University, New Orleans 70112, USA
    3 Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an 710068, China; Scientific and Technology Transfer Office, Shaanxi Provincial People’s Hospital, Xi’an 710068, China
    4 Atherosclerosis Integrated Chinese and Western Medicine Key Research Laboratory, Research Office of Shaanxi Administration of Traditional Chinese Medicine, Xi’an 710003, China
    5 Traditional Chinese Medicine Inheritance and Innovation Platform, Shaanxi Provincial People’s Hospital, Xi’an 710068, China
    6 Shaanxi Belt and Road Joint Laboratory of Precision Medicine for Cardiovascular and Cerebrovascular Diseases; Xi’an 710068, China

Received date: 2024-03-22

  Accepted date: 2024-09-08

  Online published: 2025-05-21

Supported by

National Natural Scientific Foundation of China: Mechanisms of Macrophage-Mediated Vascular Smooth Muscle Cells Phenotypic Conversion in Advanced Glycation End Products-induced Atherosclerosis and Therapeutic Effects of Targeted Gene Silencing(82070858);Youth Scientific Research and Innovation Team Program of Shaanxi Province: Diabetes-Related Atherosclerosis Basic Research and Application Research Team(2022-SLRH-LJ-014)

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Abstract

OBJECTIVE: To investigate the protective effect of matrine on coronary microvascular dysfunction (CMD) induced by advanced glycation end products (AGEs) in a mouse model of ischemia with non-obstructive coronary artery disease (INOCA), with a focus on the underlying mechanisms, particularly the endoplasmic reticulum (ER) stress protein kinase R-like ER kinase (PERK)/ nuclear factor of activated T-cells (NFAT) signaling pathway.
METHODS: An INOCA model was established in mice, and CMD was induced by peritoneal injections of AGEs. Matrine was administered daily via intraperitoneal injections. Coronary microcirculation was evaluated using coronary flow velocity reserve (CFVR), and cardiac microvascular endothelial cells (CMECs) were isolated for assessment of apoptosis, inflammation, oxidative stress, and microthrombosis. Markers of ER stress and the PERK/NFAT pathway were examined through immunoblotting, immunofluorescence, and enzymatic assays. The effect of matrine were further evaluated in CMECs treated with AGEs and the PERK agonist.
RESULTS: Matrine treatment significantly improved CFVR and reduced CMD in AGEs-exposed INOCA mice. In CMECs, matrine attenuated AGEs-induced apoptosis, inflammation, and microthrombosis. It also suppressed intracellular reactive oxygen species (ROS) generation, ER stress markers, and PERK/NFAT signaling. Matrine's effects were concentration-dependent and partially reversed by the PERK agonist, confirming its action through the ER stress pathway. No significant toxicities were observed with matrine administration.
CONCLUSION: Matrine attenuates AGEs-induced CMD in INOCA by suppressing the ROS-mediated ER stress PERK/NFAT signaling pathway in CMECs. This study highlights matrine’s potential as a therapeutic agent for CMD in diabetic cardiovascular complications.

Key words： glycation end products, advanced; matrine; endoplasmic reticulum stress; coronary microvascular dysfunction; cardiac microvascular endothelial cells

Cite this article

Haixia DU , Chuan QIU , Yanpeng MA , Shuo PAN , Xiqiang WANG , Junkui WANG , Zhongwei LIU . Matrine alleviates coronary microvascular dysfunction in ischemia with non-obstructive coronary artery disease mice induced by advanced glycation end products via inhibition of the reactive oxygen species-mediated endoplasmic reticulum stress in cardiac microvascular endothelial cells[J]. Journal of Traditional Chinese Medicine, 2025 , 45(3) : 473 -484 . DOI: 10.19852/j.cnki.jtcm.2025.03.006

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