Li Qi Huo Xue Di Wan (LQHXDW), a Chinese herbal medicine, is commonly used to treat symptoms such as palpitations, chest tightness, chest pain, and shortness of breath. However, its potential to reduce ischemia or hypoxia‐induced cardiac injury and remodeling, along with the precise mechanisms involved, remains unclear. This study aims to investigate the effects of LQHXDW on cardiac injury and remodeling induced by ischemia or hypoxia, both in vivo and in vitro, and to elucidate the underlying mechanisms. The mouse heart was subjected to ischemia for 14 days, showing evident myocardial injury and notable cardiac remodeling, accompanied by a reduction in cardiac function; these phenomena were reversed in the presence of LQHXDW. In the cultured cardiomyocyte exposed to hypoxia, incubation with LQHXDW increased the cell viability and reduced lactate dehydrogenase release. Mechanistically, LQHXDW exerted inhibitory effect on the phosphorylation levels of RIPK1, RIPK3, and MLKL as well as oxidative stress in the mice hearts suffered ischemia and the cultured cardiomyocytes exposed to hypoxia. Using the methods of ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight‐mass spectrometry, network pharmacology, and cellular thermal shift assay, phenethyl caffeate and isoliquiritigenin were identified as the potential active compounds in LQHXDW that counteract necroptosis. Based on these observations, we conclude that LQHXDW protects the heart against ischemia or hypoxia‐induced cardiac injury and remodeling through suppression of the RIPK1/RIPK3/MLKL pathway‐dependent necroptosis and oxidative stress.

中文翻译：

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中草药 Li Qi Huo Xue Di Wan 通过减少坏死性凋亡的机制改善缺血或缺氧引起的心脏损伤和重塑


李七火血地丸 （LQHXDW） 是一种中草药，常用于治疗心悸、胸闷、胸痛和呼吸急促等症状。然而，它减少缺血或缺氧诱导的心脏损伤和重塑的潜力，以及所涉及的确切机制，仍不清楚。本研究旨在探讨 LQHXDW 对体内和体外缺血或缺氧诱导的心脏损伤和重塑的影响，并阐明其潜在机制。小鼠心脏缺血 14 天，显示明显的心肌损伤和明显的心脏重塑，伴有心脏功能下降;这些现象在 LQHXDW 存在下被逆转。在暴露于缺氧的培养心肌细胞中，与 LQHXDW 孵育增加了细胞活力并减少了乳酸脱氢酶的释放。从机制上讲，LQHXDW 对小鼠心脏缺血和培养的心肌细胞缺氧的 RIPK1 、 RIPK3 和 MLKL 磷酸化水平以及氧化应激产生抑制作用。使用超高效液相色谱-四极杆飞行时间-质谱、网络药理学和细胞热转移测定的方法，确定咖啡酸苯乙酯和异甘草素是 LQHXDW 中对抗坏死性凋亡的潜在活性化合物。基于这些观察结果，我们得出结论，LQHXDW 通过抑制 RIPK1/RIPK3/MLKL 通路依赖性坏死性凋亡和氧化应激来保护心脏免受缺血或缺氧诱导的心脏损伤和重塑。