网络药理学和分子对接技术研...类真菌对疾病的潜在作用机制_楚建芝.pdf

Research paper 研究论文 22 January 2023,42(1):365-382 菌物学报 Mycosystema ISSN1672-6472 CN11-5180/Q Doi:10.13346/j.mycosystema.220373 资助项目：山东省现代农业产业技术体系食用菌产业体系岗位专家项目(鲁农科教字202126 号)；山东省中医药科技项目(M-2022040)；东西部协作科技项目(wskjdxbxm2022006,wskjdxbxm2022007)This work was supported by the Edible Fungus Industrial System Post Expert of Modern Agricultural Industrial Technology System of Shandong Province,Genetic Breeding Post,Lunong Technology(2021 No.26),the Shandong Province TCM Science and Technology Project(M-2022040),and the East-West Cooperative Science and Technology Project(wskjdxbxm2022006,wskjdxbxm2022007).*Corresponding author.E-mail:;#Co-first author ORCID:ZHANG Rui(0000-0002-6302-1269)Received:2022-09-30;Accepted:2022-10-27 Copyright 2023 Institute of Microbiology,CAS.All rights reserved.| Http:/journals- Tel:+86-10-64807521 菌物学报 365 张蕊 理学博士，鲁东大学农学院及菌物科学研究院副教授，主要从事药用真菌中活性物质的分离、分析及其生物活性的实验及理论研究，研究工作集中于桑黄、牛樟芝、柽柳核纤孔菌、灵芝、槐耳等药用菌和一系列毒蘑菇中毒素及中毒机理方面的研究。网络药理学和分子对接技术研究桑黄类真菌对疾病的潜在作用机制 楚建芝1#，郑娜1#，崔琪1，李满鑫1，李寅2，伍国超1，程显好1，张蕊1*1 鲁东大学农学院 山东省高等学校作物高产抗逆分子模块重点实验室 山东省食用菌技术重点实验室，山东 烟台 264025 2 烟台市中医医院，山东 烟台 264013 摘 要：桑黄类真菌是一类极具研究价值的药用真菌。近年来，对于桑黄类真菌的研究，多集中于对某一个物种的成分及药理活性的研究，系统比较桑黄类真菌中成分及药理活性的研究较少。本研究利用网络药理学和分子对接技术从理论上初步探讨了 5 种桑黄类真菌中化合物与疾病之间的分子作用机制。研究结果表明 5 种桑黄类真菌(栎木桑黄 Sanghuangporus quercicola、鲍姆桑黄Sanghuangporus baumii、粗毛纤孔菌 Inonotus hispidus、裂蹄木层孔菌 Tropicorus linteus、黑盖木层孔菌 Phellinus nigrians)中的 39 种有效成分，对应潜在靶点 588 个。KEGG 通路富集筛选得到 165 条通路，分析结果发现这 39 种化合物的靶点主要分布在与炎症、糖尿病、肝癌、阿尔茨海默病和衰老相关的信号通路上。筛选出桑黄类真菌中抗病的潜在靶点共 486 个，构建抗病靶点的蛋白互作(PPI)网络，并筛选出 LCK、STAT3、PTPN11、STAT1、STAT5B、MAPK1、JAK1、MAPK3、JAK3 和JAK2作为关键靶点，构建5种桑黄类真菌-化合物-关键靶点-5种疾病的网络互作图，并进行分子对接验证。筛选出的桑黄类真菌中的 12 个有效成分均可与这些关键靶点产生相互作用，其中酚类化合物居多，此外二萜类化合物异海松酸与 MAPK1 结合能力最强。因此，5 种桑黄类真菌可以通过多种化合物、多种靶点和多种途径起到抗病的作用，本研究为探索桑黄类真菌治疗和预防疾病潜在 楚建芝 等/网络药理学和分子对接技术研究桑黄类真菌对疾病的潜在作用机制 研究论文 菌物学报 366 机制提供了理论基础。关键词：桑黄；网络药理学；分子对接；靶点；信号通路 引用本文 楚建芝，郑娜，崔琪，李满鑫，李寅，伍国超，程显好，张蕊，2023.网络药理学和分子对接技术研究桑黄类真菌对疾病的潜在作用机制.菌物学报，42(1):365-382 Chu JZ,Zheng N,Cui Q,Li MX,Li Y,Wu GC,Cheng XH,Zhang R,2023.Analyses of potential mechanism of“sanghuang”in treatment of diseases based on network pharmacology and molecular docking.Mycosystema,42(1):365-382 Analyses of potential mechanism of“sanghuang”in treatment of diseases based on network pharmacology and molecular docking CHU Jianzhi1#,ZHENG Na1#,CUI Qi1,LI Manxin1,LI Yin2,WU Guochao1,CHENG Xianhao1,ZHANG Rui1*1 Shandong Key Laboratory of Edible Mushroom Technology,Key Laboratory of Molecular Module-based Breeding of High Yield and Abiotic Resistant Plants in Universities of Shandong,School of Agriculture,Ludong University,Yantai 264025,Shandong,China 2 Yantai Hospital of Traditional Chinese Medicine,Yantai 264013,Shandong,China Abstract:“sanghuang”is a kind of medicinal fungi with great research value.In recent years,researches on“sanghuang”were mainly focused on the components and pharmacological activities of certain single species,and few studies were focused on systematic comparison of components and pharmacological activities between species.In this study,the potential mechanism of five“sanghuang”species in treatment of diseases was explored based on network pharmacology and molecular docking.There were 39 effective components in 5“sanghuang”species studied(Sanghuangporus quercicola,Sanghuangporus baumii,Inonotus hispidus,Tropicorus linteus,Phellinus nigricans),and 588 potential therapeutic targets were selected.In total,165 signaling pathways were discovered via KEGG enrichment analysis.The analysis results showed that the targets of these 39 effective compounds were mainly distributed in pathways related to inflammation,diabetes mellitus,liver cancer,Alzheimer s disease and aging.A total of 486 potential targets for these diseases was screened.The protein-protein interaction(PPI)network of target protein was constructed,and the core target was screened including LCK,STAT3,PTPN11,STAT1,STAT5B,MAPK1,JAK1,MAPK3,JAK3 and JAK2.The network of five“sanghuang”species-compounds-key targets-five diseases was constructed and the core target was verified by molecular docking.All the 12 effective compounds from“sanghuang”can interact with these key targets,and most of them belong to phenolic compounds.In addition,isopimaric acid exhibited the highest binding capacity to MAPK1.The results showed that five“sanghuang”species could inhibit diseases through multi-compounds,multi-targets,and multi-pathways,providing evidence of clinical use of“sanghuang”in treating diseases.Keywords:“sanghuang”;network pharmacology;molecular docking;target;signaling pathway Research paper 22 January 2023,42(1):365-382 Mycosystema ISSN1672-6472 CN11-5180/Q 菌物学报 367 桑黄，是一类在中国、日本和韩国等地广泛使用的药用菌。从秦汉时期 神农本草经 中所记载的“桑耳”，到唐代的 药性论 中“桑黄”一词首次出现，多部中药典籍中均对其有所记载(包海鹰等 2017)。古籍中所记载的桑黄具有利尿、治疗脱肛、止血及健脾等诸多功效(Chen et al.2016)。现代药理学研究表明，桑黄具有抗氧化、抗肿瘤、抗炎、降血糖、降血压、抗衰老和保护肝脏等多种药理活性(Lin et al.2017a,2017b；贺屏雅等 2020)。虽然古籍中记载桑黄可以入药，但是对于桑黄性状的描述比较模糊，因此，仅根据古籍中的记载难以准确判定哪种桑黄是古籍中所记载的桑黄。对此，不同学者之间存在较大的争议。有学者认为只有长在桑树上的桑黄 Sanghuangporus sanghuang Sheng H.Wu,L.W.Zhou&Y