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journal article·2026-06-12Open access

Leonurine Ameliorates Doxorubicin‐Induced Cardiotoxicity via STING/NF‐κB/NLRP3 Inflammasome Signaling Pathway

Wang Jun, Chen Xiaoyang, Xu Jianglin, Yang Zhi, Tao Meijiao, He Jiale, Zhao Jiangfeng, Hei Xuanding, Xu Xuegong, Wang Wei, Li Chun

Advanced Science
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Abstract

ABSTRACT Doxorubicin‐induced cardiomyopathy (DIC) remains a dose‐limiting clinical challenge. This study reveals that cardiac vascular endothelial cells (CVECs) act as initial sensors of doxorubicin cardiotoxicity: circulating doxorubicin activates the cGAS‑STING pathway in CVECs, triggering NLRP3 inflammasome‑mediated pyroptosis and release of pathogenic extracellular vesicles that induce mitochondrial dysfunction in neighboring cardiomyocytes, establishing a self‑perpetuating injury loop. Leonurine (LEO), a natural alkaloid, is identified as a direct STING inhibitor that specifically binds the TYR261 residue, blocking both STING oligomerization and STING‑TBK1 heterodimer formation—a mechanism distinct from known STING inhibitors. LEO exerts hierarchical dual protection: directly preserving cardiomyocyte mitochondria while primarily inhibiting endothelial STING to disrupt the pathogenic loop. This endothelial‑centric strategy shifts the therapeutic paradigm from direct cardiomyocyte protection to upstream endothelial intervention, establishing LEO as a promising candidate for DIC.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: interferon and immune responses · Inflammasome and immune disorders · Pericarditis and Cardiac Tamponade

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

School of Basic Medicine Guangzhou University of Chinese Medicine Guangzhou China

State Key Laboratory of Traditional Chinese Medicine Syndrome Guangzhou University of Chinese Medicine Guangzhou China

Institute of Formula and Syndrome School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine Guangzhou China

Chinese Medicine Guangdong Laboratory Hengqin China

Science and Technology Innovation Center Zhengzhou Hospital of Traditional Chinese Medicine (Zhengzhou Hospital of TCM Affiliated to Henan University of Chinese Medicine) Zhengzhou China

Henan Provincial Key Laboratory of Traditional Chinese Medicine for Cardiovascular Diseases Zhengzhou Hospital of Traditional Chinese Medicine Zhengzhou China

Department of Cardiovascular Medicine Zhengzhou Traditional Chinese Medicine Hospital Zhengzhou China

Department of Cardiology The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou China

Institute of Traditional Chinese Medicine Beijing University of Chinese Medicine Beijing China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Youth Science Fund Project

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