Zhang Y, Xia S, Zhang L, Chen M, Liu X, Gao Q, Ye H
Department of Physiology, Bengbu Medical University, Bengbu 233000, China.
Key Laboratory of Basic and Clinical Cardiovascular Diseases, Bengbu Medical University, Bengbu 233000, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Aug 20;44(8):1571-1581. doi: 10.12122/j.issn.1673-4254.2024.08.16.
To explore the mechanism underlying the protective effect of flos (LJF) extract against doxorubicin (DOX) -induced liver injury in mice.
Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets, based on which the protein-protein interaction (PPI) network was constructed using STRING database for screening the core targets using Cytoscape software. DAVID database was used for bioinformatics analysis, and the core components and core targets were verified using molecular docking study. In a mouse model of DOX-induced liver injury, the effect of LJF extract on liver pathologies, serum levels of ALT and AST, and hepatic expressions of HYP, ROS, TNF-α, IL-6, COL-Ⅳ and P53 proteins were evaluated using HE and Masson staining, ELISA, and Western blotting.
We identified 12 core targets from 43 intersection genes involving cancer pathway, IL-17 signaling pathway, and TNF signaling pathways. Molecular docking study suggested that 10 core components of LJF could bind to different core targets. The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis, increased ROS content, and enhanced expressions of TNF-α, IL-6, HYP, COL-Ⅳ and P53 proteins in the liver tissue. All these changes in the mouse models were significantly alleviated by treatment with LJF extract, suggesting obviously lowered levels of oxidative stress, inflammation and fibrosis in the liver tissues.
LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53, TNF and IL-6 to reduce liver oxidative stress, inflammation and fibrosis.
探讨连钱草（LJF）提取物对阿霉素（DOX）诱导的小鼠肝损伤保护作用的潜在机制。
采用网络药理学方法获取LJF靶点与疾病靶点的交集基因，在此基础上利用STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络，使用Cytoscape软件筛选核心靶点。利用DAVID数据库进行生物信息学分析，并通过分子对接研究验证核心成分和核心靶点。在DOX诱导的肝损伤小鼠模型中，采用苏木精-伊红（HE）和Masson染色、酶联免疫吸附测定（ELISA）及蛋白质免疫印迹法，评估LJF提取物对肝脏病理、血清谷丙转氨酶（ALT）和谷草转氨酶（AST）水平以及肝脏组织中羟脯氨酸（HYP）、活性氧（ROS）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、Ⅳ型胶原（COL-Ⅳ）和P53蛋白表达的影响。
我们从涉及癌症通路、白细胞介素-17信号通路和肿瘤坏死因子信号通路的43个交集基因中鉴定出12个核心靶点。分子对接研究表明，LJF的10种核心成分可与不同的核心靶点结合。DOX诱导的肝损伤小鼠血清AST和ALT水平升高，伴有明显的肝损伤和纤维化，ROS含量增加，肝脏组织中TNF-α、IL-6、HYP、COL-Ⅳ和P53蛋白表达增强。LJF提取物治疗可显著减轻小鼠模型中的所有这些变化，表明肝脏组织中的氧化应激、炎症和纤维化水平明显降低。
LJF提取物能够通过下调Trp53、TNF和IL-6来减轻DOX诱导的小鼠肝损伤，从而降低肝脏氧化应激、炎症和纤维化水平。
