天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (增刊2): 119-127.

• 数据研究 • 上一篇    下一篇

基于网络药理学方法探究白首乌影响颌下腺分泌功能的作用机制

张   霞1,2,袁   岸1,2,雷紫琴1,2, 杨若聪1,2,黄张君3,沈才洪3,曾   南1,2*   

  1. 1西南特色中药资源国家重点实验室;2成都中医药大学药学院,成都 611137;3泸州品创科技有限公司,泸州 646000
  • 出版日期:2022-12-07 发布日期:2022-12-07
  • 基金资助:
    国家自然科学基金(81473399);四川省固态酿造技术创新中心建设项目(2021ZYD0102)

Exploring the mechanism of bunge auriculate root affecting the secretory function of submandibular gland based on network pharmacology

ZHANG Xia1,2,YUAN An1,2,LEI Zi-qin1,2,YANG Ruo-cong1,2,HUANG Zhang-jun3,SHEN Cai-hong3,ZENG Nan1,2*   

  1. 1State Key Laboratory of Southwestern Chinese Medicine Resources;2School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;3Luzhou Pinchuang Technology Co.,Ltd.,Luzhou 646000,China
  • Online:2022-12-07 Published:2022-12-07

摘要:

运用网络药理学方法探究白首乌对颌下腺分泌功能的潜在作用机制,并通过小鼠实验进行初步验证。通过检索白首乌活性成分的相关信息并分析类药性,获得疾病相关靶点,与活性成分靶点进行蛋白质相互作用(PPI)分析。并对交集靶点基因进行富集分析,找到口干症状的体内靶点,发掘出疾病-靶点-化合物的对应关系,找到与口干症相关的成分(群)。开展动物实验验证,观察其对小鼠饮水量及颌下腺组织中毒蕈碱型乙酰胆碱受体M3(CHRM3)mRNA表达、水通道蛋白5(AQP5)蛋白表达的影响。研究分析得到白首乌10个成分符合类药五原则,发现药物靶点80个,疾病靶点3 539个,两者共同靶点24个,涉及细胞凋亡信号通路、p53信号通路、VEGF信号通路等22条信号通路,能通过调控CHRM3、胺氧化酶(MAOB)、谷氨酸受体2亚基(GRIA2)、内皮型一氧化氮合酶(NOS3)相关靶点影响唾液分泌。实验表明,白首乌醇提物连续灌服可使小鼠唾液分泌有一定提高趋势,上调颌下腺CHRM3 mRNA及其下游信号传导效应蛋白AQP5蛋白表达水平,且对颌下腺组织无病理损伤。研究结果初步表明白首乌的主要活性成分可能通过影响CHRM3、AQP5来促进唾液分泌。

关键词: 网络药理学, 白首乌, 口干症, 颌下腺, 唾液分泌

Abstract:

The potential mechanism of bunge auriculate root on the secretory function of the submandibular gland was investigated by using the method of network pharmacology,and the preliminary verification was carried out by mouse experiments.By searching the relevant information of the active components of bunge auriculate root,analyzing the drug-likeness,and obtaining disease-related targets,and protein-protein interaction (PPI) analysis was carried out with the targets of the active components.We also performed enrichment analysis of intersecting target genes to find in vivo targets of dry mouth symptoms,uncover disease-target-compound correspondence,and find the ingredients (groups) associated with dry mouth.Then,animal experiments were carried out to verify its effects on water intake and the expression of muscarinic acetylcholine receptor M3 (CHRM3) mRNA and aquaporin 5 (AQP5) protein in submaxillary gland tissues of mice.The study analysis obtained 10 components in line with the rule of five,found 80 drug targets,3 539 disease targets,and 24 common targets for both,involving 22 signaling pathways such as apoptosis,p53 signaling pathway,and VEGF signaling pathway,and affecting salivary fraction by regulating CHRM3,amine oxidase (MAOB),glutamate receptor 2 (GRIA2),and nitric oxide synthase,endothelial (NOS3) related targets.The experiment showed that continuous oral ethanol extract of bunge auriculate root caused a certain tendency to increase salivary secretion in mice,and upregulated the expression level of CHRM3 mRNA and its downstream signal transduction effector protein AQP5 protein in the submandibular gland,without pathological damage to submandibular gland tissue.It is suggested that the main active constituents of bunge auriculate root could promote salivary secretion by affecting CHRM3 and AQP5.

Key words: network pharmacology, bunge auriculate root, xerostomia (dry mouth), submaxillary salivary gland, salivary secretion

中图分类号:  R285