Journal of ethnopharmacology · 2026
Ligustilide alleviates myocardial infarction by targeting S100A9 to inhibit neutrophil activation and attenuate the inflammatory cascade.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Guo Ying, Li Mengyao, Fang Zhirui, Liu Ting, Wang Tianyu, Zhi Hui, Chen Ping, Wang Shaoxia, Chen Lu, Sun Wangjie, Liu Qi, Wang Hong
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Suxiao Jiuxin Pills (SJP), as a classic Chinese patent medicine formula, is clinically used to treat angina pectoris and myocardial ischemia (MI). However, its pharmacodynamic basis and potential molecular mechanisms remain incompletely elucidated. Bioinformatics analysis identified S100A9 as a key MI target, and ligustilide (Lig) (primary active component of SJP) as its specific ligand.
AIM OF THE STUDY: This study aims to elucidate the molecular mechanism by which Lig targets S100A9 to inhibit neutrophil activation and alleviate MI.
MATERIALS AND METHODS: Bioinformatics analysis of human MI datasets and murine MI model validation identified S100A9 as SJP's potential target for alleviating early post-MI inflammatory injury. Molecular docking, SPR, MD simulations, and CETSA were used toscreened SJP's S100A9-targeting components. In MI models, S100A9 expression (infarcted myocardium/peripheral blood) was quantified by qRT-PCR, Western blot, and ELISA. Cardiac function was evaluated by echocardiography, TTC staining, enzymatic and histopathological assays. Flow cytometry assessed post-MI myocardial neutrophil/monocyte infiltration and neutrophil S100A9 expression. NET formation and NLRP3 inflammasome-associated molecules expression were assessed by Western blot and qRT-PCR, respectively. The mRNA expression of inflammatory cytokines was analyzed by qRT-PCR. Serum IL-1β levels were quantified by ELISA. Flow cytometry analyzed bone marrow (BM)/spleen neutrophil/monocyte infiltration and BM cell subset proportions. qRT-PCR determined mRNA levels of BM proliferation- and differentiation-related factors. An ischemia-reperfusion (I/R) model further confirmed the cardioprotective effect of Lig targeting S100A9 to inhibit neutrophil activation.
RESULTS: S100A9 was the key target mediating SJP's cardioprotection, with its major bioactive component Lig as a specific S100A9 ligand. Post-MI, Lig downregulated S100A9, attenuated inflammation and apoptosis, reduced infarct size, and improved cardiac function. It suppressed myocardial neutrophil/monocyte infiltration, NET formation, and NLRP3 inflammasome activation, and decreased cardiac TNF-α/IL-1β and serum IL-1β levels. Furthermore, it reduced inflammatory cell proportions in BM and spleen, increased BM Lin- and LSK cells, decreased megakaryocyte-erythroid progenitor ratios, and downregulated granulocyte proliferation/differentiation-related mRNA. In the I/R model, Lig exerted consistent cardioprotection via targeting S100A9.
CONCLUSION: Lig, the principal bioactive component of SJP, confers cardioprotection by targeting S100A9 to inhibit neutrophil activation and attenuate acute myocardial inflammatory injury post-MI.
AIM OF THE STUDY: This study aims to elucidate the molecular mechanism by which Lig targets S100A9 to inhibit neutrophil activation and alleviate MI.
MATERIALS AND METHODS: Bioinformatics analysis of human MI datasets and murine MI model validation identified S100A9 as SJP's potential target for alleviating early post-MI inflammatory injury. Molecular docking, SPR, MD simulations, and CETSA were used toscreened SJP's S100A9-targeting components. In MI models, S100A9 expression (infarcted myocardium/peripheral blood) was quantified by qRT-PCR, Western blot, and ELISA. Cardiac function was evaluated by echocardiography, TTC staining, enzymatic and histopathological assays. Flow cytometry assessed post-MI myocardial neutrophil/monocyte infiltration and neutrophil S100A9 expression. NET formation and NLRP3 inflammasome-associated molecules expression were assessed by Western blot and qRT-PCR, respectively. The mRNA expression of inflammatory cytokines was analyzed by qRT-PCR. Serum IL-1β levels were quantified by ELISA. Flow cytometry analyzed bone marrow (BM)/spleen neutrophil/monocyte infiltration and BM cell subset proportions. qRT-PCR determined mRNA levels of BM proliferation- and differentiation-related factors. An ischemia-reperfusion (I/R) model further confirmed the cardioprotective effect of Lig targeting S100A9 to inhibit neutrophil activation.
RESULTS: S100A9 was the key target mediating SJP's cardioprotection, with its major bioactive component Lig as a specific S100A9 ligand. Post-MI, Lig downregulated S100A9, attenuated inflammation and apoptosis, reduced infarct size, and improved cardiac function. It suppressed myocardial neutrophil/monocyte infiltration, NET formation, and NLRP3 inflammasome activation, and decreased cardiac TNF-α/IL-1β and serum IL-1β levels. Furthermore, it reduced inflammatory cell proportions in BM and spleen, increased BM Lin- and LSK cells, decreased megakaryocyte-erythroid progenitor ratios, and downregulated granulocyte proliferation/differentiation-related mRNA. In the I/R model, Lig exerted consistent cardioprotection via targeting S100A9.
CONCLUSION: Lig, the principal bioactive component of SJP, confers cardioprotection by targeting S100A9 to inhibit neutrophil activation and attenuate acute myocardial inflammatory injury post-MI.