摘要
目的基于数据挖掘、网络药理学探讨国家专利中药复方治疗慢性心力衰竭(CHF)的用药规律及作用机制。方法通过检索国家知识产权局专利数据库收集有关中药治疗CHF的专利复方,使用Excel 2016、IBMSPSS Statistics 26.0、IBM SPSS Modeler 18.0软件对专利复方数据进行频次、关联规则和系统聚类等分析,归纳国家专利中药复方治疗CHF的用药规律,并获取核心药物组合。同时运用网络药理学技术探讨数据挖掘筛选出的核心药物组合治疗CHF的活性成分及其作用靶点,并采用分子对接技术加以验证。结果共纳入治疗CHF的国家专利中药复方222首,涉及中药441味。其治疗药物以补虚药、活血化瘀药为主,其中高频药物有黄芪、丹参等。药物以温性为主,药味以甘味多见,多归于心经、肺经。关联分析得到黄芪-葶苈子-丹参、茯苓-白术-黄芪、茯苓-白术-桂枝等药物组合;聚类分析得到麦冬-五味子、当归-川芎-赤芍-三七、附子-干姜-人参、黄芪-丹参-葶苈子等7首新处方;筛选出核心药物组合为黄芪-丹参-葶苈子。网络药理学结果显示,黄芪-丹参-葶苈子核心药物组合治疗CHF的主要活性成分有香紫苏醇、丹参酮ⅡA、山柰酚、丹酚酸A、槲皮素、二高-γ-亚麻酸、木犀草素等;治疗的核心靶点有EGFR、CASP3、ESR1、SRC、PPARG、PTGS2、MMP9、GSK3β、HSP90AA1等;主要作用于钙离子、细胞凋亡、cAMP等信号通路。分子对接结果显示,黄芪-丹参-葶苈子核心药物组合的活性成分香紫苏醇、二高-γ-亚麻酸与ESR1,丹酚酸A与EGFR,丹参酮ⅡA与PPARG的结合活性最好。结论CHF中药专利复方多采用补虚药、活血化瘀药治疗CHF,黄芪-丹参-葶苈子核心药物组合的主要活性成分可通过作用于EGFR、CASP3、ESR1等关键靶点,参与钙离子等信号通路的调控,进而发挥治疗作用。
Objective To investigate the medication rules and mechanism of national patent Chinese herbal compounds in treating chronic heart failure(CHF)based on data mining and network pharmacology.Methods Patent Chinese herbal compounds for CHF treatment were collected from the China National Intellectual Property Administration Patent Database.Excel 2016,IBM SPSS Statistics 26.0,and IBM SPSS Modeler 18.0 were used to analyze frequency,association rules,and systematic clustering of the patent compound data.Core drug combinations were identified.Network pharmacology was employed to explore active components and therapeutic targets of the core combinations derived from data mining,followed by molecular docking validation.Results A total of 222 national patent Chinese herbal compounds for CHF treatment were included,involving 441 medicinals.Deficiency-supplementing medicinals,and blood-activating and stasis-resolving medicinals were predominated,with high-frequency medicinals including Astragali Radix and Salviae Militiorrhizae Radix et Rhizoma.The medicinals were primarily warm in nature,sweet in flavor,and targeted the heart and lung meridians.Association analysis yielded combinations such as Astragali Radix-Descurainiae Semen Lepidii Semen-Salviae Militiorrhizae Radix et Rhizoma,Poria-Atractylodis Macrocephalae Rhizoma-Astragali Radix,and Poria-Atractylodis Macrocephalae Rhizoma-Cinnamomi Ramulus.Cluster analysis generated seven new prescriptions,including Ophiopogonis Radix-Schisandrae Chinensis Fructus,Angelicae Sinensis Radix-Chuanxiong Rhizoma-Paeoniae Radix Rubra-Notoginseng Radix et Rhizoma,Aconiti Lateralis Radix Praeparata-Zingiberis Rhizoma-Ginseng Radix et Rhizoma,Astragali Radix-Salviae Militiorrhizae Radix et Rhizoma-Descurainiae Semen Lepidii Semen.The core combination was Astragali Radix-Salviae Militiorrhizae Radix et Rhizoma-Descurainiae Semen Lepidii Semen.The network pharmacology results indicate that the main active components of the Astragali Radix-Salviae Militiorrhizae Radix et Rhizoma-Descurainiae Semen Lepidii Semen core drug group for treating CHF include sclareol,tanshinone IIA,kaempferol,salvianolic acid A,quercetin,dihomo-γ-linolenic acid,and luteolin.The core therapeutic targets are EGFR,CASP3,ESR1,SRC,PPARG,PTGS2,MMP9,GSK3β,and HSP90AA1.These components primarily act on signaling pathways such as calcium ion signaling,apoptosis,and cAMP.Molecular docking results show that the active components of the Astragali Radix-Salviae Militiorrhizae Radix et Rhizoma-Descurainiae Semen Lepidii Semen core drug group,sclareol and dihomo-γ-linolenic acid,have the best binding activity with ESR1,salvianolic acid A with EGFR,and tanshinone IIA with PPARG.Conclusion National patent Chinese herbal compounds for CHF predominantly utilize deficiency-supplementing and blood-activating herbs.The core combination Astragali Radix-Salviae Militiorrhizae Radix et Rhizoma-Descurainiae Semen Lepidii Semen exerts therapeutic effects by targeting EGFR,CASP3,ESR1,and calcium ion signaling pathways.
作者
魏蒙召
丁健
刘玉龙
葛岚
程晓昱
WEI Mengzhao;DING Jian;LIU Yulong;GE Lan;CHENG Xiaoyu(First Clinical College of Anhui University of Traditional Chinese Medicine,Hefei 230038 Anhui,China;First Affiliated Hospital of Anhui University of Traditional Chinese Medicine,Hefei 230031 Anhui,China;Anhui Cheng′s Internal Medicine School Workshop,Hefei 230031 Anhui,China)
出处
《中药新药与临床药理》
北大核心
2025年第5期814-824,共11页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家中医药管理局高水平中医药重点学科建设项目(国中医药人教函[2023]85号)
安徽省中医药学术流派传承工作室建设项目(皖中医药发展秘[2021]30号)
安徽省卫生健康省财政支持重点科研项目(AHWJ2023A10087)
安徽省高等学校自然科学研究重点项目(KJ2022AH050507)。
关键词
专利复方
慢性心力衰竭
用药规律
数据挖掘
网络药理学
分子对接
黄芪
丹参
葶苈子
patent compound
chronic heart failure
medication rules
data mining
network pharmacology
molecular docking
Astragali Radix
Salviae Militiorrhizae Radix et Rhizoma
Descurainiae Semen Lepidii Semen
作者简介
魏蒙召,男,硕士研究生,研究方向:中医药防治心血管疾病。Email:hllywmz@163.com;通信作者:程晓昱,女,教授,博士研究生导师,研究方向:中医药防治心血管疾病。Email:cxy478@163.com;共同通信作者:葛岚,女,主任医师,硕士研究生导师,研究方向:中医药防治心血管疾病。Email:gelan311@126.com。
