[1]于鲲鹏 于永铎.基于网络药理学讨论白花蛇舌草治疗溃疡性结肠炎的作用机制[J].陕西中医药大学学报,2022,(03):087-96.[doi:10.13424/j.cnki.jsctcm.2022.03.022]
　YU Kunpeng YU Yongduo.Discussion on Mechanism of Hedyotis diffusa in Treatment of Ulcerative Colitis Based on Network Pharmacology[J].Journal of Shaanxi University of Traditional Chinese Medicine,2022,(03):087-96.[doi:10.13424/j.cnki.jsctcm.2022.03.022]
点击复制

基于网络药理学讨论白花蛇舌草治疗溃疡性结肠炎的作用机制
分享到：

《陕西中医药大学学报》[ISSN:2096-1340/CN:61-1501/R]

卷:
期数:
2022年03期
页码:
087-96
栏目:
论著
出版日期:
2022-05-26

文章信息/Info

Title:
Discussion on Mechanism of Hedyotis diffusa in Treatment of Ulcerative Colitis Based on Network Pharmacology
文章编号:
2096-1340(2022)03-0087-10
作者:
于鲲鹏1 于永铎2
1.辽宁中医药大学，辽宁 沈阳 110847；
2.辽宁中医药大学附属医院，辽宁 沈阳 110847
Author(s):
YU Kunpeng1 YU Yongduo2
1.Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;
2.Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China
关键词:
关键词：溃疡性结肠炎; 白花蛇舌草; 网络药理学; 作用机制; 信号通路
Keywords:
Key words： Ulcerative colitis; Hedyotis diffusa; Network pharmacology; Mechanism of action; Signal pathway
分类号:
R285.5
DOI:
10.13424/j.cnki.jsctcm.2022.03.022
文献标志码:
A
摘要:
摘 要：目的 基于网络药理学技术分析讨论白花蛇舌草治疗溃疡性结肠炎（ulcerative colitis，UC）的潜在治疗靶标及作用机制。方法 通过中药系统药理学数据库与分析平台（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP）筛查白花蛇舌草有效成分以及对应靶点。利用GeneCards，CTD，DisGeNET数据库，以“ulcerative colitis”为检索词查询疾病靶点蛋白，得到疾病相关靶点。使用Venny2.1.得出白花蛇舌草与UC的共同靶点作为预测靶点，利用STRING数据库构建PPI蛋白互作网络，并利用Cytoscape构建白花蛇舌草治疗UC的药物-有效成分-靶点网络图。应用Cluster Profiler R包进行GO功能富集分析和KEGG信号通路分析，并进行可视化作图。结果 ①经筛选分析得出白花蛇舌草有效化合物7个，对应的靶基因123个，治疗UC的预测靶基因17017个。药物与UC的相交靶点119个。②PPI网络中的核心基因主要有白细胞介素6（IL-6），血管内皮生长因子A（VEGFA），肿瘤蛋白P53（TP53）,肿瘤坏死因子（TNF）等。③GO功能富集分析显示白花蛇舌草对UC的预测靶基因所涉及的生物学过程（BP）主要有细胞对药物的反应，对营养水平的反应，活性氧代谢过程，对活性氧的反应等；细胞组分（CC）包括膜筏，膜区，微膜区，突触膜，突触后膜的组成部分等；分子功能（MF）主要涉及到神经递质受体活性，G蛋白偶联胺受体活性，丝氨酸水解酶活性，丝氨酸型内肽酶活性等。KEGG通路富集分析结果显示有糖尿病并发症中的AGE-RAGE信号通路，松弛素信号通路，IL-17信号通路，TNF信号通路，HIF-1信号通路等主要通路可能与白花蛇舌草治疗UC相关。结论 白花蛇舌草可能通过IL-6,VEGFA,TP53,TNF,EDF,JUN,MAPK1等多靶点，以及AGE RAGE信号通路、松弛素信号通路，HIF-1信号通路，IL-17信号通路，PI3K-Akt信号通路等通路共同发挥作用而治疗UC，为后续深入研究打下理论基础。
Abstract:
Abstract： Objective To analyze and discuss the potential therapeutic targets and mechanism of Hedyotis diffusa in the treatment of ulcerative colitis based on network pharmacological technology.Methods The effective components and corresponding targets of Hedyotis diffusa were screened by TCMSP.Using GeneCards，CTD，DisGeNET databases,the disease target proteins were queried with “ulcerative colitis” as the key word,and the disease-related targets were obtained.Use Venny 2.1,the common target of Hedyotis diffusa and ulcerative colitis was obtained as the prediction target,the PPI protein interaction network was constructed by using STRING database,and the drug active component target network diagram of Hedyotis diffusa in the treatment of ulcerative colitis was constructed by using Cytoscape.Cluster Profiler R package is used for GO function enrichment analysis and KEGG signal pathway analysis,and visual drawing is carried out.Results ①After screening and analysis,there were 7 effective compounds of Hedyotis diffusa,123 corresponding target genes and 17017 predicted target genes for the treatment of UC.There were 119 intersecting targets between drugs and ulcerative colitis.②The core genes in PPI network mainly include interleukin 6 (IL6),vascular endothelial growth factor A (VEGFA),tumor protein p53 (TP53),tumor necrosis factor (TNF),etc.③GO functional enrichment analysis showed that the biological process (BP) involved in the prediction target gene of Hedyotis diffusa to UC mainly included cell response to drugs,response to nutritional level,reactive oxygen species metabolism process,response to reactive oxygen species,etc;Cell components (CC) include membrane raft,membrane area,micromembrane area,synaptic membrane,components of postsynaptic membrane,etc;Molecular function (MF) mainly involves neurotransmitter receptor activity,G protein coupled amine receptor activity,serine hydrolase activity,serine endopeptidase activity and so on.KEGG pathway enrichment analysis showed that AGE-RAGE signal pathway,relaxin signal pathway,IL-17 signal pathway,TNF signal pathway,HIF-1 signal pathway and other major pathways in diabetes complications may be related to the treatment of ulcerative colitis with Hedyotis diffusa.Conclusion Hedyotis diffusa may play a role in the treatment of ulcerative colitis through multiple targets such as IL6,VEGFA,TP53,TNF,EDF,JUN,MAPK1 as well as AGE RAGE signal pathway,relaxin signal pathway,HIF-1 signal pathway,IL-17 signal pathway and PI3K-Akt signal pathway,which lays a theoretical foundation for further research.

参考文献/References:

［1］Ungaro R,Mehandru S,Allen PB,et al.Ulcerative colitis［J］.Lancet,2017,389(10080):1756-1770.
［2］Joseph D,Feuerstein.Ulcerative colitis-science direct［J］.Mayo Clinic proceedings,2019,94(7):1357-1373.
［3］何永恒,凌光烈.中医肛肠科学［M］.2版.北京:清华大学出版社,2012.
［4］程琪庆,程春松,刘智祖,等.白花蛇舌草和水线草的鉴别与药用进展比较［J］.中草药,2017,48(20):4328-4338.
［5］国家药典委员会.中华人民共和国药典2020年版［S］.一部.北京：中国医药科技出版社，2020.
［6］王信,马传江,杨培民,等.白花蛇舌草抗炎、抗肿瘤作用研究进展［J］.中国现代应用药学,2020,37(19):2420-2427.
［7］侯山岭.中药白花蛇舌草化学成分及药理活性研究进展［J］.中医临床研究,2018,10(6):140-141.
［8］World Federation of Chinese Medicine Societies.网络药理学评价方法指南［J］.世界中医药,2021,16(4):527-532.
［9］Kaplan GG.The global burden of IBD:from 2015 to 2025［J］.Nature Reviews Gastroenterology & Hepatology,2015,12(12):720-727.
［10］Du L,Ha C.Epidemiology and pathogenesis of ulcerative colitis［J］.Gastroenterology Clinics of North America,2020,49(4):643-654.
［11］李军祥,陈誩.溃疡性结肠炎中西医结合诊疗共识意见(2017年)［J］.中国中西医结合消化杂志,2018,26(2):105-111，120.
［12］Wehkamp J,Stange EF.Recent advances and emerging therapies in the non-surgical management of ulcerative colitis［J］.F1000Research,2018,7:1207.
［13］Dal Buono A,Roda G,Argollo M,et al.Treat to target or “treat to clear” in inflammatory bowel diseases:one step further?［J］.Expert Review of Gastroenterology & Hepatology,2020,14(9):807-817.
［14］Kucharzik T,Koletzko S,Kannengiesser K,et al.Ulcerative colitis-diagnostic and therapeutic algorithms［J］.Deutsches rzteblatt International,2020,117(33/34):564-574.
［15］Hibiya S,Matsuyama Y,Fujii T,et al.5‐aminosalicylate-intolerant patients are at increased risk of colectomy for ulcerative colitis［J］.Alimentary Pharmacology & Therapeutics,2021，53(1):103-113.
［16］甄建华,黄光瑞.溃疡性结肠炎中医病名、病因、病机的古今比较和回顾［J］.环球中医药,2019,12(8):1286-1289.
［17］崔世超,柳越冬.溃疡性结肠炎的中医治疗思路［J］.辽宁中医杂志,2017,44(7):1381-1384.
［18］于永铎,满如,郑洪，新等.以痈论治溃疡性结肠炎活动期湿热毒证的病因病机研究［J］.中国肛肠病杂志,2020,40(3):75-76.
［19］Dicarlo M,Teti G,Verna G,et al.Quercetin exposure suppresses the inflammatory pathway in intestinal organoids from Winnie mice［J］.International Journal of Molecular Sciences,2019,20(22):5771.
［20］Ding K,Tan YY,Ding Y,et al.Β-Sitosterol improves experimental colitis in mice with a target against pathogenic bacteria［J］.Journal of Cellular Biochemistry,2019,120(4):5687-5694.
［21］Antwi AO,Obiri DD,Osafo N,et al.Stigmasterol inhibits lipopolysaccharide-induced innate immune responses in murine models［J］.International Immunopharmacology,2017,53:105-113.
［22］赵亚娇,李楠.IL-6/STAT3信号通路在溃疡性结肠炎治疗中的新进展［J］.中华消化病与影像杂志(电子版),2015,5(4):45-48.
［23］Mateescu RB,Bastian AE,Nichita L,et al.Vascular endothelial growth factor-key mediator of angiogenesis and promising therapeutical target in ulcerative colitis［J］.Romanian Journal of Morphology and Embryology,2017,58(4):1339-1345.
［24］Zdravkovic ND,Jovanovic IP,Radosavljevic GD,et al.Potential dual immunomodulatory role of VEGF in ulcerative colitis and colorectal carcinoma［J］.International Journal of Medical Sciences,2014,11(9):936-947.
［25］Hirsch D,Hardt J,Sauer C,et al.Molecular characterization of ulcerative colitis-associated colorectal carcinomas［J］.Modern Pathology,2021,34(6):1153-1166.
［26］陈明琪,崔云,陈晓宇.TNF-α在炎症性肠病发生、发展中的作用机制［J］.胃肠病学,2020,25(3):187-190.
［27］Pugliese D,Felice C,Papa A,et al.Anti TNF-α therapy for ulcerative colitis:current status and prospects for the future［J］.Expert Review of Clinical Immunology,2017,13(3):223-233.
［28］Wang ZW,Zhang JQ,Chen L,et al.Glycine suppresses AGE/RAGE signaling pathway and subsequent oxidative stress by restoring Glo1 function in the aorta of diabetic rats and in HUVECs［J］.Oxidative Medicine and Cellular Longevity,2019,2019:4628962.
［29］Peng K,Zhuo M,Li M,et al.Histone demethylase JMJD2D activates HIF1 signaling pathway via multiple mechanisms to promote colorectal cancer glycolysis and progression［J］.Oncogene.2020，39(47):7076-7091.
［30］Zhang Z,Yao L,Yang JH,et al.PI3K/Akt and HIF-1 signaling pathway in hypoxia-ischemia (Review)［J］.Molecular Medicine Reports,2018,18(4):3547-3554.
［31］Chen QY,Duan XY,Fan H,et al.Oxymatrine protects against DSS-induced colitis via inhibiting the PI3K/AKT signaling pathway［J］.International Immunopharmacology,2017,53:149-157.
［32］李华,周云,温省初,等.白花蛇舌草通过PI3K/Akt信号通路抑制人非霍奇金淋巴瘤Raji细胞增殖［J］.现代肿瘤医学,2020,28(20):3495-3499.
［33］Park S,Regmi SC,Park SY,et al.Protective effect of 7-O-succinyl macrolactin A against intestinal inflammation is mediated through PI3-kinase/Akt/mTOR and NF-κB signaling pathways［J］.European Journal of Pharmacology,2014,735:184-192.
［34］Zhang LC,Hu LX,Xiao AJ,et al.Effect of medicated thread moxibustion of Chinese Zhuang Minority medicine on colonic inflammatory impairment and Th17/IL-17F signaling in rats with ulcerative colitis［J］.Zhen Ci Yan Jiu,2020,45(3):188-193.
［35］Sakurai T,Higashitsuji H,Kashida H,et al.The oncoprotein gankyrin promotes the development of colitis-associated cancer through activation of STAT3［J］.Oncotarget,2017,8(15):24762-24776.
［36］Abboud C,Brochoire L,Drouet A,et al.Analgesic effect of central relaxin receptor activation on persistent inflammatory pain in mice:behavioral and neurochemical data［J］.PAIN Reports,2021,6(2):937.
［37］Ng HH,Shen M,Samuel CS,et al.Relaxin and extracellular matrix remodeling:Mechanisms and signaling pathways［J］.Molecular and Cellular Endocrinology,2019,487:59-65.
［38］Li P,Zhao G,Chen FF,et al.Rh-relaxin-2 attenuates degranulation of mast cells by inhibiting NF-κB through PI3K-AKT/TNFAIP3 pathway in an experimental germinal matrix hemorrhage rat model［J］.Journal of Neuroinflammation,2020,17(1):250.
［39］Zelová H,Hoek J.TNF-α signalling and inflammation:interactions between old acquaintances［J］.Inflammation Research,2013,62(7):641-651.
［40］Setia S,Nehru B,Sanyal SN.Upregulation of MAPK/Erk and PI3K/Akt pathways in ulcerative colitis-associated colon cancer［J］.Biomedicine & Pharmacotherapy,2014,68(8):1023-1029.
［41］孙婕怡,胥冰.“健脾益气、解毒通络”方保留灌肠对溃疡性结肠炎患者血清IL-8、TNF-α含量变化及生存质量的影响［J］.世界中西医结合杂志,2018,13(7):960-964.

相似文献/References:

[1]马玲 裴瑞霞.裴瑞霞教授分期论治溃疡性结肠炎经验[J].陕西中医药大学学报,2022,(02):027.[doi:10.13424/j.cnki.jsctcm.2022.02.006]
　MA Ling PEI Ruixia.Professor PEI Ruixia’s Experience in Treating Ulcerative Colitis by Stages[J].Journal of Shaanxi University of Traditional Chinese Medicine,2022,(03):027.[doi:10.13424/j.cnki.jsctcm.2022.02.006]
[2]郭心怡 黄雅慧 刘长兴 赵丹 姚东.黄雅慧教授从“治未病”思想防治溃疡性结肠炎临床经验[J].陕西中医药大学学报,2023,(03):014.[doi:10.13424/j.cnki.jsctcm.2023.03.003]
　GUO Xinyi HUANG Yahui LIU Changxing ZHAO Dan YAO Dong.Professor HUANG Yahuis Clinical Experiencein Preventing and Treating Ulcerative Colitis fromPerspective of “Preventive Treatment of Disease”[J].Journal of Shaanxi University of Traditional Chinese Medicine,2023,(03):014.[doi:10.13424/j.cnki.jsctcm.2023.03.003]

备注/Memo

备注/Memo:
基金项目：辽宁省重点研发计划项目（2020JH2/10300062）
更新日期/Last Update: 2022-05-30