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Network pharmacology based investigation into the bioactive compounds and molecular mechanisms of Schisandrae Chinensis Fructus against drug-induced liver injury.
Bioorganic Chemistry ( IF 5.1 ) Pub Date : 2019-12-31 , DOI: 10.1016/j.bioorg.2019.103553
Xiankuan Li 1 , Huijuan Yang 1 , Jiongchang Xiao 1 , Jian Zhang 1 , Juan Zhang 1 , Mei Liu 1 , Yanchao Zheng 2 , Lin Ma 1
Affiliation  

OBJECTIVE To investigate the against Drug-induced liver injury ingredients and their functional mechanisms in S. Chinensis Fructus. METHODS Liquid chromatograph-mass spectrometry analysis was performed on S. Chinensis Fructus extrac. The "Components-Target-Disease" network model was constructed by network pharmacology-based approaches. String analysis was performed to reveal enrichment of these target proteins, protein-protein interactions, pathways and related diseases. And experiment of APAP-induced drug-induced liver injury was to be verified. RESULTS Cytoscape was used to determine the potential protein targets for these components in S. Chinensis Fructus, indicating that 17 against Drug-induced liver injury compounds in S. Chinensis Fructus regulate 52 diabetes-related proteins in 15 signal pathways and involve 14 core key targets. Verification experiment results that S. Chinensis Fructus prevented the elevation of serum biochemical parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), purine nucleoside phosphorylase (PNP) and alkaline phosphatase (ALP) against acute liver failure. Additionally, S. Chinensis Fructus reduced the content of malondialdehyde (MDA), increased the levels of the Superoxide dismutase (SOD) and Glutathione (GSH), and inhibited the production of proinflammatory cytokines in APAP-induced hepatotoxicity. CONCLUSION The mechanisms of S. Chinensis Fructus against Drug-induced liver injury were involved in the regulation of multiple targets, especially affecting the ErbB signaling pathways. The active ingredients of S. Chinensis Fructus may play a role against Drug-induced liver injury by participating in the regulation of inflammatory factors, oxidative stress.

中文翻译:

基于网络药理学的五味子对药物性肝损伤的生物活性化合物和分子机制的研究。

目的研究中华绒螯蟹抗药性肝损伤成分及其功能机制。方法采用液相色谱-质谱联用技术对中华绒螯蟹进行提取。通过基于网络药理学的方法构建了“组分-靶标-疾病”网络模型。进行字符串分析以揭示这些靶蛋白的富集,蛋白-蛋白相互作用,途径和相关疾病。并验证了APAP引起的药物性肝损伤的实验。结果Cytoscape用于确定中华绒螯蟹中这些成分的潜在蛋白质靶标,表明17种抗药性中华绒螯蟹肝损伤化合物可通过15个信号途径调节52种与糖尿病相关的蛋白质,并涉及14个核心关键靶点。验证实验结果表明,中华五味子可以防止血清生化指标升高,包括天冬氨酸转氨酶(AST),丙氨酸转氨酶(ALT),嘌呤核苷磷酸化酶(PNP)和碱性磷酸酶(ALP)对抗急性肝衰竭。此外,中华绒螯蟹降低了丙二醛(MDA)的含量,增加了超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的水平,并抑制了APAP诱导的肝毒性中促炎细胞因子的产生。结论中华绒螯蟹抗药物性肝损伤的机制参与了多个靶标的调控,尤其是影响ErbB信号通路。S的有效成分。
更新日期:2020-01-01
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