基于网络药理学、分子对接与PRM靶向蛋白验证探讨苁蓉舒痉颗粒治疗帕金森病的作用机制  

Mechanism of Congrong Shujing granules in treatment ofParkinson’s disease based on network pharmacology,molecular docking and parallel reaction monitoring technology

作　　者：刘海鑫 倪慧心 周美 范自立 高正涛 吴方真 林瑶[1] 许茜[1] 蔡晶 LIU Hai-xin;NI Hui-xin;ZHOU Mei;FAN Zi-li;GAO Zheng-tao;WU Fang-zhen;LIN Yao;XU Qian;CAI Jing(College of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Rheumatology and Endocrinology Dept,the Second People′s Hospital of Fujian Province,Fuzhou 350001,China;Third Affiliated People’s Hospital of Fujian University of Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学中西医结合学院,福建福州350122 [2]福建省第二人民医院风湿内分泌科,福建福州350001 [3]福建中医药大学附属第三人民医院,福建福州350122

出　　处：《中国药理学通报》2025年第2期365-372,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年项目(No 81904263);福建省中医药科研项目计划(No 2021zyjc02);福建中医药大学中医健康管理学联合省级临床重点专科建设项目(老年病科)(No XJG2023018);福建中医药大学校管课题青年项目(No X2023010)。

摘　　要：目的结合网络药理学、分子对接与PRM蛋白相对定量分析探索苁蓉舒痉颗粒(Congrong Shujing granules,CSGs)治疗帕金森病(Parkinson’s disease,PD)的作用机制。方法通过数据库获取CSGs的有效成分和PD的靶点。取药物与疾病的交集靶点,进行“药物-活性成分-靶点”网络和蛋白互作网络的构建与分析,将交集靶点基因导入David数据库进行GO和KEGG富集分析,并将主要成分与关键靶点进行分子对接。将27只SD大鼠随机分为正常组9只、模型组9只和治疗组9只,于疗程d 1、7、14采用PRM蛋白相对定量分析法检测大鼠黑质纹状体关键靶蛋白特异性肽段表达量的变化情况。结果CSGs主要成分为丹参醛、黄芩素、槲皮素和山柰酚等;治疗PD最为关键的靶点为TP53、AKT1、EGFR、HSP90AA1和STAT3;KEGG分析主要富集:MAPK、PI3K-Akt和神经营养因子等信号通路。核心成分与核心靶点的分子对接表明,药物与靶点的结合具有较好活性。PRM分析发现ASK1、JNK1,JNK3目标肽段表达量各组间存在差异(P<0.05)。结论CSGs可通过ASK1-JNK信号通路,缓解内质网应激,抑制细胞凋亡,发挥神经保护作用。Aim To explore the mechanism of Congrong Shujing granule(CSGs)in the treatment of Parkinson’s disease(PD)by network pharmacology,molecular docking and parallel reaction monitoring(PRM)technology.Methods The active components of CSGs and the target genes of Parkinson’s disease were obtained through the database.The intersection targets of drugs and diseases were selected to construct the“drug-active ingredient-target”and protein interaction network.The intersection target genes were imported into David database for GO and KEGG enrichment analysis,and the main components were docked with key targets.27 SD rats were randomly divided into the normal group(n=9),model group(n=9)and treatment group(n=9).On day 1,7 and 14 of treatment,PRM analysis was used to detect the changes in the specific peptides of key target proteins in the substantia nigra of rats.Results The main components of CSGs wereTanshialdehyde,Baicalein,Quercetin and Kaempferol.The most important targets for the treatment of PD were TP53,AKT1,EGFR,HSP90AA1 and STAT3.KEGG analysis mainly enriched MAPK,PI3K-Akt and neurotrophic factor signaling pathway.The molecular docking between core components and core targets showed that the binding of drugs and targets had good activity.PRM analysis of key proteins found that the target peptide expression levels of ASK1,JNK1 and JNK3 were different among groups(P<0.05).Conclusion CSGs can alleviate ERS,inhibit apoptosis and play a neural protective role through the ASK1-JNK pathway.

关 键 词：帕金森病 苁蓉舒痉颗粒 网络药理学 分子对接 PRM ASK1-JNK信号通路 

分 类 号：R-332[医药卫生] R282.71R319R329.24R745.7