RESEARCH PAPER

Integrating Network Pharmacology and Molecular Docking to Explorer Mechanism of Anti-Inflammation of Matrine in Dairy Cow Production

  • ZHAO Zixuan ,
  • YANG Jiarui ,
  • JIANG Linshu ,
  • TONG Jinjin
Expand
  • Beijing Key Laboratory of Dairy Cow Nutrition, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China

Received date: 2022-05-20

  Online published: 2022-12-15

Abstract

The aim of this study was to investigate the anti-inflammatory mechanism of matrine in dairy production using network pharmacology and molecular docking techniques. The main targets of matrine were searched by logging into the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) database and supplemented by logging into PubChem and PharmMapper databases. At the same time, inflammation-related targets were obtained by searching GeneCards and DisGeNET databases, and the intersection target of matrine and inflammation is a candidate target of matrine for the treatment of inflammation in dairy cows. Matrine anti-inflammatory intersection targets were input into STRING database and protein-protein interaction (PPI) network was constructed. Core targets of this network were screened by CytoNCA module in Cytoscape 3.9.1 software. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of matrine anti-inflammatory targets were performed using David database. The core targets and active components were docked by Autodock Tools. The results showed that there were 71 targets related to matrine's anti-inflammatory effect. PPI network analysis showed that albumin (ALB), tumor necrosis factor (TNF), MYC proto-oncogene basic helix-loop helix transcription factor (MYC), cysteine-aspartate proteinase 3 (CASP3), cyclin D1 (CCND1), CD44 and interleukin-6 (IL-6) were the core targets of anti-inflammatory effects of matrine. GO functional enrichment analysis showed that the target involved 62 biological processes (BP), 16 cellular components (CC) and 12 molecular functions (MF). A total of 71 signaling pathways were obtained by KEGG pathway enrichment analysis. The molecular docking prediction results showed that matrine stably bound to the key core targets and had a good interaction with them. In this study, network pharmacology and molecular docking technology were used to reveal the mechanism of the anti-inflammatory effect of matrine through multiple targets and multiple pathways, which provides a reference for further clinical application of matrine in dairy cow production.

Cite this article

ZHAO Zixuan , YANG Jiarui , JIANG Linshu , TONG Jinjin . Integrating Network Pharmacology and Molecular Docking to Explorer Mechanism of Anti-Inflammation of Matrine in Dairy Cow Production[J]. Chinese Journal of Animal Nutrition, 2022 , 34(12) : 7872 -7885 . DOI: 10.3969/j.issn.1006-267x.2022.12.037

References

[1] 李剑杰.推进"减抗"养殖存在的问题及对策[J].江西农业, 2020(24):57-58. LI J J.Problems and countermeasures in promoting "reduced resistance" aquaculture[J].Jiangxi Agriculture, 2020(24):57-58.(in Chinese)
[2] 马广强, 牛玲, 宋莹莹, 等.苦参碱通过MAPK/mTOR信号通路诱导IMCD3细胞自噬及机制研究[J].中国免疫学杂志, 2022, 38(3):282-287. MA G Q, NIU L, SONG Y Y, et al.Study on mechanism of matrine induces autophagy of IMCD3 cells through MAPK/mTOR signaling pathway[J].Chinese Journal of Immunology, 2022, 38(3):282-287.(in Chinese)
[3] 赵清梅, 余永涛.苦参碱和氧化苦参碱对奶牛子宫内膜炎致病菌体外抑制试验[J].动物医学进展, 2017, 38(1):65-68. ZHAO Q M, YU Y T.Antibacterial activity of matrine and oxymatrine on pathogenic bacteria causing cow endometritis in vitro[J].Progress in Veterinary Medicine, 2017, 38(1):65-68.(in Chinese)
[4] 姚红艳, 李诗举, 李秀富, 等.苦参碱对断奶仔猪腹泻及小肠肥大细胞的影响[J].黑龙江畜牧兽医, 2010(7):143-144. YAO H Y, LI S J, LI X F, et al.Effects of matrine on diarrhea and small intestinal mast cells of weaned piglets[J].Heilongjiang Animal Science and Veterinary Medicine, 2010(7):143-144.(in Chinese)
[5] 权鑫.苦参碱抗牛乳头状瘤病毒感染C127细胞研究[D].硕士学位论文.哈尔滨:东北农业大学, 2015. QUAN X.Research on matrine resisting bovine papillomavirus infecting C127 cells[D].Master's Thesis.Harbin:Northeast Agricultural University, 2015.(in Chinese)
[6] 詹静慧, 王佩佩, 崔振华, 等.氧化苦参碱治疗小鼠胶原诱导性关节炎的作用机制[J].中国中药杂志, 2021, 46(22):5895-5901. ZHAN J H, WANG P P, CUI Z H, et al.Mechanism of oxymatrine in treatment of collagen-induced arthritis in mice[J].China Journal of Chinese Materia Medica, 2021, 46(22):5895-5901.(in Chinese)
[7] 卢金霞, 何芳, 冯峰, 等.苦参碱对奶牛乳腺上皮细胞增殖、凋亡及抗氧化能力的影响[J].西北农林科技大学学报(自然科学版), 2018, 46(7):1-6, 14. LU J X, HE F, FENG F, et al.Effect of matrine on proliferation, apoptosis and antioxidant ability of bovine mammary epithelial cells[J].Journal of Northwest A&F University(Natural Science Edition), 2018, 46(7):1-6, 14.(in Chinese)
[8] 卢金霞.苦参碱干预金黄色葡萄球菌对奶牛乳腺上皮细胞粘附作用的研究[D].硕士学位论文.银川:宁夏大学, 2017. LU J X.Effects of matrine on the adhesion of Staphylococcus aureus to bovine mammary epithelial cells[D].Master's Thesis.Yinchuan:Ningxia University, 2017.(in Chinese)
[9] 朱海林, 王振洲, 高爽, 等.中药作用靶点的预测及发现方法研究进展[J].特产研究, 2015, 37(4):64-68. ZHU H L, WANG Z Z, GAO S, et al.Advances in methods of predicting and discovering targets of traditional Chinese medicine[J].Special Wild Economic Animal and Plant Research, 2015, 37(4):64-68.(in Chinese)
[10] 解静, 高杉, 李琳, 等.网络药理学在中药领域中的研究进展与应用策略[J].中草药, 2019, 50(10):2257-2265. XIE J, GAO S, LI L, et al.Research progress and application strategy on network pharmacology in Chinese materia medica[J].Chinese Traditional and Herbal Drugs, 2019, 50(10):2257-2265.(in Chinese)
[11] 庄延双, 蔡宝昌, 张自力.网络药理学在中药研究中的应用进展[J].南京中医药大学学报, 2021, 37(1):156-160. ZHUANG Y S, CAI B C, ZHANG Z L.Application progress of network pharmacology in traditional Chinese medicine research[J].Journal of Nanjing University of Traditional Chinese Medicine, 2021, 37(1):156-160.(in Chinese)
[12] RU J L, LI P, WANG J A, et al.TCMSP:a database of systems pharmacology for drug discovery from herbal medicines[J].Journal of Cheminformatics, 2014, 6:13.
[13] CONSORTIUM U.UniProt:a worldwide hub of protein knowledge[J].Nucleic Acids Research, 2019, 47(D1):D506-D515.
[14] STELZER G, ROSEN N, PLASCHKES I, et al.The GeneCards suite:from gene data mining to disease genome sequence analyses[J].Current Protocols in Bioinformatics, 2016, 54:1.30.1-1.30.33.
[15] PIÑERO J, RAMÍREZ-ANGUITA J M, SAVCH-PITARCH J, et al.The DisGeNET knowledge platform for disease genomics:2019 update[J].Nucleic Acids Research, 2020, 48(D1):D845-D855.
[16] FRANCESCHINI A, SZKLARCZYK D, FRANKILD S, et al.STRING v9.1:protein-protein interaction networks, with increased coverage and integration[J].Nucleic Acids Research, 2013, 41:D808-D815.
[17] TANG Y, LI M, WANG J X, et al.CytoNCA:a cytoscape plugin for centrality analysis and evaluation of protein interaction networks[J].Biosystems, 2015, 127:67-72.
[18] SHANNON P, MARKIEL A, OZIER O, et al.Cytoscape:a software environment for integrated models of biomolecular interaction networks[J].Genome Research, 2003, 13(11):2498-2504.  
[19] TONG J J, SUN M W, ZHANG H, et al.Proteomic analysis of bovine mammary epithelial cells after in vitro incubation with S. agalactiae:potential biomarkers[J].Veterinary Research, 2020, 51(1):98.
[20] NIU H, ZHANG H, WU F X, et al.Proteomics study on the protective mechanism of soybean isoflavone against inflammation injury of bovine mammary epithelial cells induced by Streptococcus agalactiae[J].Cell Stress and Chaperones, 2021, 26(1):91-101.  
[21] 孙倩, 乔青.苦参碱注射液治疗中晚期舌癌术后患者血清IL-8和Smad4水平的变化[J].慢性病学杂志, 2020, 21(11):1767-1769. SUN Q, QIAO Q.Changes of serum IL-8 and Smad4 levels in patients with advanced tongue cancer after matrine injection[J].Chronic Pathematology Journal, 2020, 21(11):1767-1769.(in Chinese)
[22] 孙铭维, 童津津, 蒋林树, 等.壳聚糖抗无乳链球菌引起的奶牛乳腺上皮细胞炎性反应[J].动物营养学报, 2020, 32(3):1216-1226. SUN M W, TONG J J, JIANG L S, et al.Anti-inflammatory response of chitosan in bovine mammary epithelial cells induced by Streptococcus agalactiae[J].Chinese Journal of Animal Nutrition, 2020, 32(3):1216-1226.
[23] 孙铭维, 童津津, 蒋林树, 等.体外法研究壳聚糖对无乳链球菌诱导的奶牛乳腺上皮细胞炎性损伤的保护作用[J].动物营养学报, 2020, 32(3):1204-1215. SUN M W, TONG J J, JIANG L S, et al.In vitro study on protective effect of chitosan against inflammation injury of bovine mammary epithelial cells induced by Streptococcus agalactiae[J].Journal of Animal Nutrition, 2020, 32(3):1204-1215.(in Chinese)
[24] 刘旭, 梁跃辉, 赵晓秋, 等.苦参碱类TNF-α抑制剂的合成、抗炎活性评价和分子对接研究[J].计算机与应用学, 2016, 33(5):521-524. LIU X, LIANG Y H, ZHAO X Q, et al.Synthesis of TNF-α inhibitors, anti inflammatory activity evaluation and molecular docking study of matrine derivatives[J].Computers and Applied Chemistry, 2016, 33(5):521-524.(in Chinese)
[25] JIANG K F, GUO S, YANG J, et al.Matrine alleviates Staphylococcus aureus lipoteichoic acid-induced endometritis via suppression of TLR2-mediated NF-κB activation[J].International Immunopharmacology, 2019, 70:201-207.
[26] 于晓红, 白云静, 程鹏, 等.苦参碱对奶牛子宫内膜上皮细胞抗炎作用及其机制[J].北京农学院学报, 2015, 30(3):35-39. YU X H, BAI Y J, CHENG P, et al.Anti-inflammatory effect of matrine on the bovine endometrial epithelial cell and its mechanism[J].Journal of Beijing University of Agriculture, 2015, 30(3):35-39.(in Chinese)
[27] MIHARA M, HASHIZUME M, YOSHIDA H, et al.IL-6/IL-6 receptor system and its role in physiological and pathological conditions[J].Clinical Science, 2012, 122(4):143-159.  
[28] 丁园园, 张荣生, 张冬华, 等.基于网络药理学和分子对接探讨苦参碱抗新冠病毒机制研究[J].中药药理与临床, 2020, 36(4):18-23. DING Y Y, ZHANG R S, ZHANG D H, et al.Mechanism study of matrine against SARS-CoV-2 based on network pharmacology and molecular docking[J].Pharmacology and Clinics of Chinese Materia Medica, 2020, 36(4):18-23.(in Chinese)
[29] 曹建, 朱晓燃, 杨振寰, 等.基于网络药理学探讨清肝化瘀颗粒治疗肝癌的作用机制[J].中草药, 2021, 52(7):2039-2052. CAO J, ZHU X R, YANG Z H, et al.An exploration on mechanisms of Qinggan Huayu Granule in treating liver cancer based on network pharmacology[J].Chinese Traditional and Herbal Drugs, 2021, 52(7):2039-2052.(in Chinese)
[30] 李仁礼, 向晓辉, 周子栋, 等.氧化苦参碱对过氧化氢刺激的胰腺腺泡细胞高迁移率族蛋白B1表达和释放的影响[J].中华胰腺病杂志, 2020, 20(1):27-32. LI R L, XIANG X H, ZHOU Z D, et al.Effects of oxymatrine on the expression and release of high mobility group box 1 in pancreatic acinar cells stimulated by hydrogen peroxide[J].Chinese Journal of Pancreatology, 2020, 20(1):27-32.(in Chinese)
[31] 张想军, 冯峰, 周学章.苦参碱对金黄色葡萄球菌入侵BMECs的干预作用[J].西北农林科技大学学报(自然科学), 2020, 48(9):17-23. ZHANG X J, FENG F, ZHOU X Z.Effect of matrine on invasion of bovine mammary epithelial cells by Staphylococcus aureus[J].Journal of Northwest A&F University(Natural Science Edition), 2020, 48(9):17-23.(in Chinese)
[32] 何智慧, 王春平, 张海燕.一氧化氮与奶牛健康养殖[J].饲料研究, 2017(3):10-14. HE Z H, WANG C P, ZHANG H Y.Nitric oxide and healthy dairy farming[J].Feed Research, 2017(3):10-14.(in Chinese)
[33] 王宇, 郑世民.白细胞介素-8及其在动物疾病发生中的作用[J].中国畜牧兽医, 2010, 37(3):198-201. WANG Y, ZHENG S M.Interleukin-8 and role in the pathogesis of animal diseases[J].China Animal Husbandry & Veterinary Medicine, 2010, 37(3):198-201.(in Chinese)
[34] 袁海, 宋雪梅, 姜俊芳, 等.丝裂原活化蛋白激酶信号通路及其与热应激反应的关系[J].中国畜牧兽医, 2012, 39(1):114-118. YUAN H, SONG X M, JIANG J F, et al.Mitogen-activated protein kinases signaling pathways and the relationship with the heat stress response[J].China Animal Husbandry & Veterinary Medicine, 2012, 39(1):114-118.(in Chinese)
[35] 瞿小祥, 孔东波, 鲁小红, 等.苦参碱经TLR4/NF-κB通路对膀胱癌小鼠免疫机制的调控作用[J].东南大学学报(医学版), 2021, 40(6):813-819. QU X X, KONG D B, LU X H, et al.Effects of matrine on bladder cancer mice through TLR4/NF-κB pathway and its regulation of immunity[J].Journal of Southeast University(Medical Science Edition), 2021, 40(6):813-819.(in Chinese)
[36] WU J J, ZHU S L, GU F F, et al.Cross-tissue single-cell transcriptomic landscape reveals the key cell subtypes and their potential roles in the nutrient absorption and metabolism in dairy cattle[J].Journal of Advanced Research, 2022, 37:1-18.
[37] ZHOU J L, MA W X, WANG X C, et al.Matrine suppresses reactive oxygen species (ROS)-mediated MKKs/p38-induced inflammation in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages[J].Medical Science Monitor, 2019, 25:4130-4136.
[38] CHU Y J, JING Y L, ZHAO X Y, et al.Modulation of the HMGB1/TLR4/NF-κB signaling pathway in the CNS by matrine in experimental autoimmune encephalomyelitis[J].Journal of Neuroimmunology, 2021, 352:577480.
[39] 周艳, 牟宽厚, 韩丹, 等.苦参碱可抑制Th17所诱导的角质形成细胞IL-17RAIL-21RIL-22R1的表达[J].西安交通大学学报(医学版), 2014, 35(5):695-699. ZHOU Y, MOU K H, HAN D, et al.Matrine inhibits Th17 cytokine-induced IL-17RA, IL-21R and IL-22R1 expressions of keratinocytes[J].Journal of Xi'an Jiaotong University(Medical Sciences), 2014, 35(5):695-699.(in Chinese)
Outlines

/