威尔德（Willd. ex Schltdl.）通过KEAP1-NFE2L2介导的铁死亡调节减轻肝损伤：网络药理学与实验验证

Willd. ex Schltdl. Mitigates Liver Injury via KEAP1-NFE2L2-Mediated Ferroptosis Regulation: Network Pharmacology and Experimental Validation.

作者信息

Du Hongxu, Yang Kunzhao, Yang Jingyi, Wan Junjie, Pan Yu, Song Weijie, Xu Shuang, Chen Cheng, Li Jiahui

机构信息

Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing 402460, China.

Institute of Traditional Chinese Veterinary Medicine, Southwest University, Chongqing 402460, China.

出版信息

Vet Sci. 2025 Apr 9;12(4):350. doi: 10.3390/vetsci12040350.

Liver injury poses major health risks in livestock, necessitating effective therapeutic interventions. This study elucidates the hepatoprotective mechanisms of Willd. ex Schltdl. (EHW) by integrating network pharmacology, molecular docking, and experimental validation. Using a CCl-induced liver injury model mimicking veterinary clinical scenarios, EHW markedly alleviated hepatic damage, demonstrated by reduced liver index, serum ALT and AST levels, histopathological lesions, iron accumulation, inflammatory cytokines, and ferroptosis-associated gene expression. Network pharmacology identified EHW's core bioactive components (quercetin, kaempferol, and β-sitosterol) and critical targets (, , , , , and ) which were linked to ferroptosis and oxidative stress. Molecular docking revealed robust binding affinities between these compounds and ferroptosis-related proteins. validation confirmed that EHW inhibited , activated -mediated antioxidant defenses (upregulating and ), restored iron homeostasis (lowering , elevating ), and attenuated phospholipid peroxidation by suppressing and . These results indicate that EHW mitigates ferroptosis-driven liver injury via KEAP1-NFE2L2 signaling to restore iron homeostasis and reduce oxidative stress, offering a mechanistic foundation for its clinical application in veterinary hepatoprotection.

肝损伤给家畜带来重大健康风险，因此需要有效的治疗干预措施。本研究通过整合网络药理学、分子对接和实验验证，阐明了绵毛山茱萸（EHW）的肝保护机制。使用模拟兽医临床情况的四氯化碳诱导肝损伤模型，EHW显著减轻了肝损伤，表现为肝指数、血清谷丙转氨酶（ALT）和谷草转氨酶（AST）水平降低、组织病理学损伤减轻、铁蓄积减少、炎性细胞因子减少以及铁死亡相关基因表达降低。网络药理学确定了EHW的核心生物活性成分（槲皮素、山奈酚和β-谷甾醇）以及与铁死亡和氧化应激相关的关键靶点（……此处原文关键靶点信息缺失……）。分子对接显示这些化合物与铁死亡相关蛋白之间具有强大的结合亲和力。实验验证证实，EHW抑制……此处原文相关信息缺失……，激活Nrf2介导的抗氧化防御（上调……此处原文相关信息缺失……和……此处原文相关信息缺失……），恢复铁稳态（降低……此处原文相关信息缺失……，升高……此处原文相关信息缺失……），并通过抑制……此处原文相关信息缺失……和……此处原文相关信息缺失……减轻磷脂过氧化。这些结果表明，EHW通过KEAP1-NFE2L2信号通路减轻铁死亡驱动的肝损伤，以恢复铁稳态并减少氧化应激，为其在兽医肝保护中的临床应用提供了机制基础。