{"title":"Lycorine improves inflammatory imbalance in diabetic cardiomyopathy by targeting ILF3.","authors":"Qian Zhou, Xuejin Jin, Miao Yuan, Huanyan Tao, Shenjie Bao, Jingnan Zhang, Zheng Xu, Nipon Chattipakorn, Yi Wang, Hong Zhu, Guang Liang","doi":"10.1016/j.phymed.2026.157976","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Diabetic cardiomyopathy (DCM) is characterized by chronic low-grade inflammation and metabolic disturbances, leading to progressive cardiac dysfunction. Lycorine (LY), a complex tetracyclic pyrrolo[de]phenanthridine alkaloid from the Amaryllidaceae family, has shown potential anti-inflammatory effects, but its role in DCM pathogenesis remains unexplored.</p><p><strong>Purpose: </strong>This study investigated the cardioprotective effect of LY in DCM and its underlying molecular mechanisms.</p><p><strong>Methods: </strong>We employed both in vitro (high glucose/palmitic acid-treated cardiomyocytes) and in vivo (streptozotocin-induced diabetic mice) models to investigate LY's cardioprotective effects. Liquid chromatography-tandem mass spectrometry, molecular docking, surface plasmon resonance binding assay, cellular thermal shift assay, and RNA interference approaches were utilized to identify the key target and mechanistic pathways.</p><p><strong>Results: </strong>In vitro and in vivo models of DCM revealed that LY significantly attenuated cardiac inflammation. Mechanistically, liquid chromatography-tandem mass spectrometry analysis revealed that LY targeted interleukin enhancer-binding factor 3 (ILF3), a critical regulator of inflammatory responses. Notably, surface plasmon resonance and cellular thermal shift assay data validated a direct interaction between LY and ILF3. By interacting with ILF3, LY enhanced nuclear factor erythroid 2-related factor 2-mediated anti-inflammatory responses while suppressing NF-κB-driven pro-inflammatory signaling, thereby restoring inflammatory homeostasis and reducing myocardial injury. Furthermore, ILF3 knockdown mimicked the protective effects of LY, and ILF3 activity was essential for LY's cardioprotective effects.</p><p><strong>Conclusion: </strong>These findings suggest that LY ameliorates DCM by modulating ILF3-dependent nuclear factor erythroid 2-related factor 2 and NF-κB crosstalk to restore inflammatory balance, suggesting its potential as a novel therapeutic agent for diabetic cardiovascular complications.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"157976"},"PeriodicalIF":11.3000,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.phymed.2026.157976","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/2/14 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Diabetic cardiomyopathy (DCM) is characterized by chronic low-grade inflammation and metabolic disturbances, leading to progressive cardiac dysfunction. Lycorine (LY), a complex tetracyclic pyrrolo[de]phenanthridine alkaloid from the Amaryllidaceae family, has shown potential anti-inflammatory effects, but its role in DCM pathogenesis remains unexplored.
Purpose: This study investigated the cardioprotective effect of LY in DCM and its underlying molecular mechanisms.
Methods: We employed both in vitro (high glucose/palmitic acid-treated cardiomyocytes) and in vivo (streptozotocin-induced diabetic mice) models to investigate LY's cardioprotective effects. Liquid chromatography-tandem mass spectrometry, molecular docking, surface plasmon resonance binding assay, cellular thermal shift assay, and RNA interference approaches were utilized to identify the key target and mechanistic pathways.
Results: In vitro and in vivo models of DCM revealed that LY significantly attenuated cardiac inflammation. Mechanistically, liquid chromatography-tandem mass spectrometry analysis revealed that LY targeted interleukin enhancer-binding factor 3 (ILF3), a critical regulator of inflammatory responses. Notably, surface plasmon resonance and cellular thermal shift assay data validated a direct interaction between LY and ILF3. By interacting with ILF3, LY enhanced nuclear factor erythroid 2-related factor 2-mediated anti-inflammatory responses while suppressing NF-κB-driven pro-inflammatory signaling, thereby restoring inflammatory homeostasis and reducing myocardial injury. Furthermore, ILF3 knockdown mimicked the protective effects of LY, and ILF3 activity was essential for LY's cardioprotective effects.
Conclusion: These findings suggest that LY ameliorates DCM by modulating ILF3-dependent nuclear factor erythroid 2-related factor 2 and NF-κB crosstalk to restore inflammatory balance, suggesting its potential as a novel therapeutic agent for diabetic cardiovascular complications.
期刊介绍：
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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