摘要
目的基于数据挖掘、网络药理学和分子对接技术,探索国家专利中治疗肺癌的中药复方的用药规律,及其潜在的物质基础和可能的作用机制。方法在国家知识产权局-专利检索及分析平台检索治疗肺癌的中药复方专利。在纳排处理和数据规范化后,应用古今医案云平台对中药复方进行中药的频次、性味、归经、功效等统计分析,以及聚类分析、关联分析、复杂网络分析等深度挖掘,归纳核心中药。从TCMSP、ETCM下载核心中药的成分和靶点并通过UniProt对靶点进行标准化,从OMIM、GeneCards和Pharmgkb下载肺癌的靶点,在微生信平台取交集靶点后,应用Metascape进行GO、KEGG富集分析,应用STRING和Cytoscape构建PPI网络和中药-成分-靶点-通路-疾病网络并筛选核心成分和核心靶点。应用PDB、PyMOL、AutoDockTools、AutoDock Vina将核心成分与核心靶点分别进行分子对接。结果共纳入485项复方专利,含中药1105味,累计频次7344次,性味主要为苦寒,归经主要为肺;综合数据挖掘的结果,归纳核心中药为黄芪、白花蛇舌草、半枝莲、白术、麦冬、甘草。6味中药共获得177个成分和388个靶点,肺癌获得2788个靶点,交集靶点219个。6味中药治疗肺癌的11个核心成分为腺苷、槲皮素、木犀草素、山奈酚、汉黄芩素、7-O-甲基异微凸剑叶莎醇、柚皮素、黄芩素、芒柄花黄素、异鼠李素,10个核心靶点为MAPK3、MAPK1、AKT1、MAPK14、STAT3、PIK3CA、RELA、TP53、RXRA、MYC、RB1,主要涉及的通路有恶性肿瘤通路、脂质与动脉硬化通路、乙型肝炎通路、PI3K-Akt信号通路、人类巨细胞病毒感染通路、卡波西肉瘤相关的疱疹病毒感染通路、MAPK信号通路等。结论国家中药复方专利治疗肺癌的用药规律与以“益气除痰”为核心的“益气化痰,活血解毒”主要治法基本相符,黄芪、白花蛇舌草、半枝莲、白术、麦冬、甘草可通过多成分、多靶点、多通路发挥对肺癌的治疗作用。
Objective To investigate the medication patterns,potential material basis and possible molecular mechanisms of national patented herbal compounds in the treatment of lung cancer based on data mining,network pharmacology and molecular docking technology.Methods Patents of herbal compounds for lung cancer were retrieved from the China National Intellectual Property Administration-Patent Search and Analysis platform.After item screening and data standardization,statistical analysis of the usage frequency,the distribution of the herbal property and flavor,meridian tropism and therapeutic action classification of the herbs from the patented compounds was performed based on the Ancient and Modern Medical Records Cloud Platform,and the deep mining such as cluster analysis,association rule analysis,and complex network analysis was also carried out for mining the core Chinese medicines.The ingredients and targets of core Chinese medicines were obtained from TCMSP and ETCM,and then the targets were standardized through UniProt.The targets for lung cancer were obtained from OMIM,GeneCards and Pharmgkb.The intersection targets obtained from Bioinformatics platform were made GO and KEGG enrichment analysis in Metascape,and the PPI network and the Chinese medicine-ingredients-targets-pathways-disease network were constructed using the STRING and Cytoscape.And then the core ingredients and core targets were screened,respectively.Finally,molecular docking between the core ingredients and core targets was performed using the PDB,PyMOL,AutoDockTools,and AutoDock Vina.Results A total of 485 patents containing 1105 Chinese medicines were included,with a cumulative frequency of 7344 times for the herbs.The Chinese medicines were mainly characterized as bitter-cold in nature and have the meridian tropism of the lung meridian.The data mining yielded 6 core herbs,and they were Radix Astragali,Herba Hedyotis Diffusae,Herba Scutellariae Barbatae,Rhizoma Atractylodis Macrocephalae,Radix Ophiopogonis,and Radix et Rhizoma Glycyrrhizae.A total of 177 components and 388 targets were identified from the 6 core herbs while 2,788 targets were identified for lung cancer,with 219 intersection targets.The 11 core ingredients from the 6 core herbs for lung cancer were adenosine,quercetin,luteolin,kaempferol,wogonin,7-O-methylisomucronulatol,naringenin,baicalein,formononetin and isorhamnetin.The 10 core targets were MAPK3,MAPK1,AKT1,MAPK14,STAT3,PIK3CA,RELA,TP53,RXRA,MYC and RB1,and mainly involved the cancer pathway,lipid and atherosclerosis pathway,hepatitis B pathway,PI3K-Akt signaling pathway,human cytomegalovirus infection pathway,Kaposi sarcoma-associated herpesvirus infection pathway,MAPK signaling pathway,etc.Conclusion The medication pattern of national patented herbal compounds in the treatment of lung cancer is basically in line with the common treatment strategy of“replenishing Qi and resolving phlegm,activating blood and removing toxin”.The 6 core herbs may exert their therapeutic effects on lung cancer through multiple ingredients,multiple targets and multiple pathways.
作者
李晏龙
李彩玉
兰玲燕
丁慧宁
夏敏
雷媛姣
綦向军
余玲
林丽珠
LI Yan-long;LI Cai-yu;LAN Ling-yan;DING Hui-ning;XIA Min;LEI Yuan-jiao;QI Xiang-jun;YU Ling;LIN Li-Zhu(The First Clinical School of Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;The First Clinical Medical School of Zhejiang Chinese Medical University,Hangzhou 310000 Zhejiang,China;School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China;School of Acupuncture-Moxibustion and Massage,Beijing University of Chinese Medicine,Beijing 100000,China;College of Traditional Chinese Medicine,Chongqing Medical University,Chongqing 400000,China;Oncology Center,the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)
出处
《中医肿瘤学杂志》
2023年第4期58-69,共12页
Journal of Oncology in Chinese Medicine
基金
国家重点研发计划(编号:2022YFC3500203)
广州市科技计划项目(编号:2023A03J0300)。
关键词
肺癌
国家专利
中药复方
用药规律
网络药理
lung cancer
national patents
Chinese medicine compounds
medication pattern
data mining
network pharmacology
molecular docking
作者简介
李晏龙(1999-),男,硕士研究生,研究方向:中西医结合防治肿瘤。Email:liyanlong595@163.com;通信作者:林丽珠,博士研究生,教授,主任中医师,研究方向:中西医结合防治肿瘤。Email:linlizhu@gzucm.edu.cn;通信作者:余玲,博士研究生,主治中医师,研究方向:中西医结合防治肿瘤。Email:yuiling@gzucm.edu.cn。
