收稿日期: 2022-10-12
修回日期: 2023-01-22
网络出版日期: 2023-09-06
基金资助
河南省高等学校青年骨干教师资助项目(2021GGJS084);河南省高等学校重点科研项目(21B310003);河南中医药大学科研苗圃工程项目(MP2021-94)
Mechanism of a Chinese patent medicine in the treatment of liver fibrosis caused by infection of Clonorchis sinensis based on network pharmacology
Received date: 2022-10-12
Revised date: 2023-01-22
Online published: 2023-09-06
Supported by
Training Program for Young scholars in Universities of Henan Province(2021GGJS084);Important Scientific Research Project of Universities in Henan Province(21B310003);Nursery Project of Scientific Research in Henan University of Chinese Medicine(MP2021-94)
为探究复方鳖甲软肝片治疗华支睾吸虫感染所致肝纤维化的药理作用和分子机制，采用TCMSP、BATMAN-TCM、Swiss、GeneCards等数据库获得复方鳖甲软肝片中11味中药的有效成分和潜在靶点以及华支睾吸虫病和肝纤维化相关靶点，筛选交集靶点构建蛋白质-蛋白质互作网络、中药-成分-靶点-疾病网络，并进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，取核心靶点与其对应化合物分子对接。结果显示，复方鳖甲软肝片有效成分、华支睾吸虫病和肝纤维化交集靶点17个，度值前5的靶点分别为半胱氨酸天冬氨酸特异性蛋白酶3（CASP3）、CXC趋化因子配体8（CXCL8）、肿瘤坏死因子（TNF）、原癌基因酪氨酸蛋白激酶（SRC）、白细胞介素10（IL-10），与其分子对接结合能最小的化合物分别是黄芩素、汉黄芩素、24-乙基胆甾-4-烯-3-酮、24-乙基胆甾-4-烯-3-酮、24-乙基胆甾-4-烯-3-酮。KEGG和GO功能富集分析显示，复方鳖甲软肝片可调控细胞凋亡和增殖，减轻炎症反应和氧化应激损伤，抑制促纤维化因子的表达等，可通过磷脂酰肌醇3激酶/蛋白激酶B（PI3K-Akt）、丝裂原活化蛋白激酶（MAPK）和Janus激酶/信号转导子和转录激活因子（JAK-STAT）等通路发挥治疗华支睾吸虫感染所致肝纤维化的作用。
李天星 , 张家明 , 徐晨曦 , 王子戈 , 郭晶洁 , 李姗 . 基于网络药理学探讨复方鳖甲软肝片治疗华支睾吸虫感染所致肝纤维化的机制[J]. 中国寄生虫学与寄生虫病杂志, 2023 , 41(4) : 510 -515 . DOI: 10.12140/j.issn.1000-7423.2023.04.020
To explore the pharmacological efficacy and molecular mechanism of FufangBiejiaRuanganPian (FBRP, a Chinese patent medicine) in the treatment of liver fibrosis caused by Clonorchis sinensis infection, we obtained the active compounds from the 11 Chinese ingredients of FBRP and their potential targets as well as clonorchiasis and liver fibrosis related targets through the TCMSP, BATMAN-TCM, Swiss and GeneCards databases. The intersection targets were screened for the construction of protein-protein interaction and drug-component-target-disease networks as well as analysis of GO and KEGG enrichments. The core targets were used for molecular docking with their corresponding compounds. The results showed 17 targets from the intersection of FBRP active components, clonorchiasis and liver fibrosis. The top 5 targets from degree ranking were cysteinyl aspartate-specific proteinase-3 (CASP3), cysteine x chemokine ligand 8 (CXCL8), tumor necrosis factor (TNF), proto-oncogene tyrosine-protein kinase src (SRC), and interleukin 10 (IL-10). The compound that showed the lowest binding energy for molecular docking with these 5 targets were respectively baicalein, wogonin, 24-ethylcholest-4-en-3-one, 24-ethylcholest-4-en-3-one, and 24-ethylcholest-4-en-3-one. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) function analysis suggested that FBRP could regulate cell apoptosis and proliferation, reduce the inflammatory response and oxidative stress injury, and inhibit the expression of pro-fibrotic factors. It could play a role in the treatment of liver fibrosis caused by infection of Clonorchis sinensis through the phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), mitogen-activated protein kinase (MAPK) and janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways.
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