基于网络药理学及分子对接技术探讨大黄治疗急性胰腺炎的可能分子机制  

Investigating the possible molecular mechanism of Rhubarb in the treatment of acute pancreatitis based on network pharmacology and molecular docking techniques

作　　者：吴波[1] 袁丽萍[2] 朱德发[3] WU Bo;YUAN Liping;ZHU Defa(Department of Emergency Medicine,First Affiliated Hospital,University of Science and Technology of China(Anhui Provincial Hospital),Hefei,Anhui 230001,China;Deartment of Pediatrics,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China;Deartment of Geriatrics Endocrinology,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China)

机构地区：[1]中国科学技术大学附属第一医院(安徽省立医院)急诊医学科,安徽合肥230001 [2]安徽医科大学第一附属医院儿科,安徽合肥230022 [3]安徽医科大学第一附属医院老年内分泌科,安徽合肥230022

出　　处：《安徽医药》2023年第6期1103-1106,I0003,共5页Anhui Medical and Pharmaceutical Journal

摘　　要：目的 应用现代网络药理学和分子模拟对接技术探索大黄在急性胰腺炎治疗中的作用机制。方法 2021年10月至2022年2月,从TCMSP数据平台检索提取大黄有效成分和药物靶标;Genecards、DisGeNET等数据平台检索提取急性胰腺炎的相关靶标。取得相关靶标的交集,以String数据库构造蛋白质作用网络,并找出关键靶点。R软件中“AnnotationHub”数据包对交集靶点进行交集基因本位(GO)及基因组百科全书(KEGG)通路富集分析。Cytoscape软件建立药物-疾病靶点网络,并得到主要作用成分;Autodock Vina分析出主要作用成分与关键靶点的结合能。用Pymol软件对关键蛋白和主要成分进行分子对接。结果共得到16个药物活性成分和62个药物靶点;疾病相关靶点7 111个,其中交集靶点55个。其中β-谷甾醇、芦荟大黄素可能为主要有效成分;关键靶标为胱天蛋白酶8(CASP8)、胱天蛋白酶-3(caspase-3)、细胞周期蛋白依赖性抑制激酶1A(CDKN1A)、肿瘤蛋白p53(TP53)、原癌基因蛋白(JUN)、原癌基因蛋白(MYC)、热休克蛋白90α(HSP90AA1)、前列腺素内过氧化物合酶2(PTGS2)。通过分子对接显示β-谷甾醇、芦荟大黄素与HSP90AA1、PTGS2、caspase-3等蛋白展现出较好的结合活性。结论 大黄可能通过其关键活性成分芦荟大黄素、β-谷甾醇等成分与HSP90AA1、PTGS2等靶蛋白相结合进而发挥对急性胰腺炎的治疗作用。Objective To explore the mechanism of Rhubarb in treating acute pancreatitis(AP)based on modern network pharmacology and molecular docking techniques.Methods From October 2021 to February 2022,the effective ingredients of Rhubarb and drug targets were retrieved from the TCMSP database;the relevant targets of acute pancreatitis were collected from Genecards,DisGeNET,and other databases.The intersection of the appropriate targets was acquired.The protein interaction network in accordance with the String Database was constructed to locate the critical target.The GO and KEGG pathway enrichment on the intersecting targets were analyzed by the"AnnotationHub"package in R software.Cytoscape software was used to build the drug-disease target network and obtain the main components.Autodock Vina analyzed the significant components'binding energy and the key targets.The molecular docking of critical proteins and major components was performed by Pymol software.Results A total of 16 drug active ingredients and 62 drug targets were retrieved;7111 disease-related targets,including 55 intersecting targets,were collected.Theβ-sitosterol and aloe-rhodopsin may be the main practical components;the key targets were CASP8,caspase-3,CDKN1A,TP53,JUN,MYC,HSP90AA1,PTGS2,and so forth.Molecular docking indicated thatβ-sitosterol and aloe-rhodopsin showed good binding activity with the proteins such as HSP90AA1,PTGS2,caspase-3.Conclusion Rhubarb may exerts its therapeutic effects on acute pancreatitis through binding of its key active components such as aloe-rhodopsin andβ-sitosterol to the target proteins like HSP90AA1 and PTGS2.

关 键 词：大黄属 胰腺炎 芦荟 谷甾醇 HSP90热休克蛋白质类 前列腺素内过氧化物合酶类 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]