红芪抗放化疗所致靶器官损伤作用机制及其“构-效-量”关系  

Study on relationship of target organ injury of mechanism and“structure-effect-dose”of Hedysari Radix during radiotherapy-chemotherapy induced

作　　者：赵沙沙 何海 王姿杨 邢耀莹 任远[1,3] 邵晶 ZHAO Sha-sha;HE Hai;WANG Zi-yang;XING Yao-ying;REN Yuan;SHAO Jing(Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China;The Co-construction and Collaborative Innovation Center of Northwest Chinese and Tibetan Medicine Ministry,Lanzhou 730000,China;Key Laboratory of Pharmacology and Toxicology of Traditional Chinese Medicine of Gansu Province,Lanzhou 730000,China;Provincial Key Laboratory of Chinese(Tibet)Medicine Chemistry and Quality Research of Higher Education Institutions in Gansu Province,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学,甘肃兰州730000 [2]西北中藏药省部共建协同创新中心,甘肃兰州730000 [3]甘肃省中药药理与毒理学重点实验室,甘肃兰州730000 [4]甘肃省高校中(藏)药化学与质量研究省级重点实验室,甘肃兰州730000

出　　处：《中国药理学通报》2024年第2期371-381,共11页Chinese Pharmacological Bulletin

基　　金：甘肃省科技计划自然科学基金项目(No 21JR11RA136);兰州市城关区科技计划项目(No 2020-2-2-2);甘肃省科技计划自然科学基金项目(No 17JR5RA163);甘肃省教育厅双一流重大科研项目(No GSSYLXM-05);甘肃省中药制药工艺工程研究中心开放课题(No ZYGY202004);中医药公共卫生服务补助专项子课题(No 2305191901);2022年甘肃中医药大学研究生创新创业基金资助项目(No 2022CX83)。

摘　　要：目的探讨红芪抗放化疗所致靶器官损伤的“成分-靶点-通路”可能性药效机制,并基于其潜在机制验证主要活性成分的“量-效”关系。方法以TCMSP、Uniprot、Swiss Target Prediction、GeneCards、Cytoscape、Omicshare等平台进行网络药理学分析;以Autodock、Pymol和Ligplot等进行分子对接;以红芪水提取物进行动物实验验证;以HPLC法对8种主要成分进行含量测定。结果确定了红芪抗放化疗所致靶器官损伤的4种活性成分、8个关键靶点、4条重点通路;分子对接显示,芒柄花素和槲皮素同时与HSP90AA1、柚皮素与MAPK3、熊果酸与TP53具有较好的结合活性;动物实验表明,胃肠因子MTL、VIP明显升高,肝肾因子Cr、BUN、AST、ALT明显降低,IL^(-1)0升高,TNF-α明显降低;含量测定结果表明,芒柄花苷含量最高(2.8848μg·g^(-1))。结论探讨了红芪抗放化疗所致靶器官损伤保护作用的“构-效”关系,并对其活性成分的“量-效”关系进行验证。Aim To explore the possible mechanism of“component-target-pathway”of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy,and to verify the“dose-effect”relationship of the main active components.Methods TCMSP,Uniprot,Swiss Target Prediction,GeneCards,Cytoscape,Omicshare and other platforms were used for network pharmacology analysis.Autodock,Pymol and Ligplot were used for molecular docking.The water extract of Radix Hedysari was used for animal experiment verification.The contents of eight main components were determined by HPLC.Results Four active components,eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy.Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1,naringenin and MAPK3,and ursolic acid and TP53.Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly,liver and kidney factors Cr,BUN,AST and ALT decreased significantly,inflammatory factor IL-10 increased significantly and TNF-αdecreased significantly.The content of ononin was the highest(2.8848μg·g-1).Conclusions This study discusses the structure-effect relationship of Hedysarum stilbene′s protective effect on target organ injury caused by radiotherapy and chemotherapy,and verifies the dose-effect relationship of its active ingredients.

关 键 词：红芪 放化疗 靶器官损伤 网络药理学 分子对接 HPLC 

分 类 号：R-332[医药卫生] R285.5R319R730.5