摘要
利用人工智能技术探究艾叶中的活性成分的药理活性及潜在作用机制。检索HIT、TCMSP、TCMIO数据库获取199种艾叶的活性成分。综合K最近邻、多层感知机、随机森林、支持向量机算法及基于Lipinski规则及Veber规则的算法模型对艾叶化合物成分进行毒性和口服利用度预测,发现其中14种成分满足无毒性且口服利用度较好。采用合成可行性分数(SAscore)模型对以上14种成分进行可合成性分析,并通过BRICS及RECAP算法分割分子片段。STP和PM数据库挖掘得到406个艾叶核心成分的作用靶点,利用Cytoscape筛出5个核心靶点为SRC、EGFR、PTPN11、HRAS和PDGFRB。GO与KEGG富集分析提示核心靶点涉及808项GO富集分析条目和EGFR酪氨酸激酶抑制剂抵抗、间隙连接、磷脂酶D、JAK/STAT等71条信号通路。分子对接结果显示艾叶活性化合物与SRC、EGFR、PTPN11、HRAS蛋白具有良好的结合能力。细胞实验证实了艾叶活性成分杜香醇在一定浓度范围内能够促进HUVEC细胞增殖,并可促进EGFR蛋白的表达。本研究揭示了艾叶活性成分的药理特性及其潜在的分子机制,为其药用开发奠定了坚实的科学基础。
To investigate the pharmacological activities and potential mechanisms of action of the active components in Artemisia argyi with artificial intelligence technology,a search was conducted in the HIT,TCMSP,and TCMIO databases,obtaining 199 active components of A.argyi.A comprehensive set of algorithms,including KNN,MLP,RF,SVM,and models based on Lipinski’s and Veber’s rules,was employed to predict the toxicity and oral bioavailability of A.argyi compounds,identifying 14 components that are non-toxic and have good oral bioavailability.The synthetic accessibility score(SAscore)model was used to analyze the synthetic accessibility of the 14 components mentioned above,and molecular segments were fragmented using BRICS and RECAP algorithms.Mining of the STP and PM databases yielded 406 target proteins for the core components of A.argyi,and Cytoscape was used to screen out 5 core targets:SRC,EGFR,PTPN11,HRAS,and PDGFRB.GO and KEGG enrichment analyses indicated that the core targets were involved in 808 GO enrichment analysis entries and 71 signaling pathways,including EGFR tyrosine kinase inhibitor resistance,gap junction,phospholipase D,and JAK/STAT.Molecular docking results showed that active compounds of A.argyi have a good binding affinity with proteins SRC,EGFR,PTPN11,and HRAS.Cellular experiments have confirmed that ledol,an active component of A.argyi,can promote the proliferation of HUVEC cells within a certain concentration range and can increase the expression of EGFR protein.This study reveals the pharmacological characteristics and potential molecular mechanisms of the active components of A.argyi and lays a solid scientific foundation for its medicinal development.
作者
张洪榕
许奇
马忠民
方朝晖
ZHANG Hongrong;XU Qi;MA Zhongmin;FANG Zhaohui(School of Medical Informatics Engineering,Anhui University of Chinese Medicine,Hefei 230012;School of Chinese Medicine,Anhui University of Chinese Medicine,Hefei 230038;Anhui Shou Airen Traditional Chinese Medicine Science and Technology Co.,Ltd.,Hefei 230031;Xin’an Institute of medicine and modernization of Chinese medicine,National Science Center’s Institute of Comprehensive Health,Hefei 230000,China)
出处
《中国药科大学学报》
北大核心
2025年第3期358-367,共10页
Journal of China Pharmaceutical University
基金
安徽省高校协同创新项目(GXXT-2020-025)
合肥综合性国家科学中心大健康研究院新安医学与中医药现代化研究所“揭榜挂帅”项目(2023CXMMTCM003)。
关键词
人工智能
艾叶
活性成分
药理特性
分子机制
artificial intelligence
Artemisia argyi
active ingredients
pharmacological properties
molecular mechanisms
