山东科学 ›› 2022, Vol. 35 ›› Issue (1): 45-55.doi: 10.3976/j.issn.1002-4026.2022.01.007

• 药理与毒理 • 上一篇    下一篇

基于网络药理学的扶正调理液作用机制及其对S180荷瘤小鼠的影响

曹铭晨1(),彭小菊1,*(),黄先菊2,柯才华2,汪川1,辛兆洋1,于振英1,潘冬琦1,崔萌纳1   

  1. 1.青岛大学附属医院,山东 青岛266000
    2.中南民族大学,湖北 武汉 430074
  • 收稿日期:2021-03-04 出版日期:2022-02-20 发布日期:2022-01-25
  • 通信作者: 彭小菊 E-mail:kisschen@vip.qq.com;13953280801@163.com
  • 作者简介:曹铭晨(1993—),男,硕士,药师,研究方向为中药学和临床药学。E-mail: kisschen@vip.qq.com
  • 基金资助:
    中央高校基本科研专项资金,国家级重大重点项目培育专项(CZP20002);青岛市科技局课题(KZD03-1)

Mechanism of Fuzheng Tiaoli Decoction based on network pharmacology and its effect on S180 tumor-bearing mice

CAO Ming-chen1(),PENG Xiao-ju1,*(),HUANG Xian-ju2,KE Cai-hua2,WANG Chuan1,XIN Zhao-yang1,YU Zhen-ying1,PAN Dong-qi1,CUI Meng-na1   

  1. 1. Affiliated Hospital of Qingdao University, Qingdao 266000,China
    2. South-Central Minzu University, Wuhan 430074,China
  • Received:2021-03-04 Online:2022-02-20 Published:2022-01-25
  • Contact: Xiao-ju PENG E-mail:kisschen@vip.qq.com;13953280801@163.com

摘要:

基于网络药理学挖掘扶正调理液的分子作用机制,应用BATMAN-TCM在线分析平台预测扶正调理液潜在靶点并构建化合物-靶点-通路-疾病相互作用网络图;应用STRING数据库构建关键靶点蛋白质-蛋白质相互作用网络,基于基因本体(gene ontology, GO)、Reactome、京都基因与基因组百科全书数据库(Kyoto encyclopedia of genes and genomes,KEGG)进行生物通路富集分析;研究扶正调理液对S180荷瘤小鼠体重、进食的影响,计算肿瘤抑制率、胸腺和脾脏指数。结果表明:扶正调理液的靶点网络主要涉及癌症(非特异性)、疼痛、乳腺癌、心血管疾病、炎症反应、前列腺癌、抑郁等疾病;涉及关键靶点如OPRK1NR3C1NR3C2ADORA1ESR1等;GO富集分析涉及细胞溶质、细胞质膜、氧化还原酶活性、跨膜转运蛋白活性、细胞氨基酸等小分子代谢过程;Reactome通路富集分析涉及神经元系统、跨化学突触的传递、神经递质受体和突触后信号传递等;KEGG通路富集分析涉及神经活动配体-受体相互作用、钙信号通路、血清素能突触、味觉转导、氨基酸代谢、唾液分泌等。动物实验结果显示:低、高剂量组小鼠的进食量、精神状态和被毛的光泽度优于阳性组及阴性组;高剂量组28 d体质量增长率显著高;低剂量、高剂量及阳性组的肿瘤抑制率分别为8.73%、19.54%、47.89%;低剂量组和高剂量组的胸腺指数低于阳性组但显著高于阴性组;高剂量组的脾脏指数显著低于阳性组。本研究提示扶正调理液可能通过影响关键靶点基因的表达,介导神经活动配体-受体相互作用、钙信号通路、血清素能突触、味觉转导、氨基酸代谢、唾液分泌等信号通路,改善焦虑、抑郁等负面心理状态,提高睡眠质量,减轻疲劳,改善食欲和营养状况,增强免疫功能,改善脾脏肿大和胸腺萎缩的状态,增强荷瘤小鼠免疫功能,抑制肿瘤的进展,体现中药复方的多靶点和整体性的作用特点,为进一步研究扶正调理液的分子作用机制提供新思路。

关键词: 扶正调理液, 抗肿瘤, 免疫, 亚健康, 网络药理学

Abstract:

This study aimed to discover the molecular mechanism of Fuzheng Tiaoli Decoction based on network pharmacology. The Bioinformatics Analysis Tool of Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) server was used to predict the potential targets of Fuzheng Tiaoli Decoction and construct a compound-target-pathway-disease interaction network diagram. The protein-protein interaction network of key targets was built using the STRING database based on gene ontology (GO), Reactome, and Kyoto encyclopedia of genes and genomes (KEGG) database for biological pathway enrichment analysis. Furthermore, the effect of Fuzheng Tiaoli Decoction on the body weight and eating habit of S180 tumor-bearing mice was studied, and the tumor inhibition rate and thymus and spleen indices were calculated. The results showed that the target network of Fuzheng Tiaoli decoction mainly involves cancer (nonspecific), analgesia, breast cancer, cardiovascular disease, inflammation, prostate cancer, depression, and other diseases and key targets such as OPRK1, NR3C1, NR3C2, ADORA1, ESR1, etc. GO enrichment analysis involved cytosol, cytoplasmic membrane, oxidoreductase activity, transmembrane transport protein activity, cellular amino acid, and other small molecule metabolism processes. Reactome pathway enrichment analysis involved neuronal systems, cross-chemical synapses transmission, neurotransmitter receptors, and post-synaptic signal transmission. KEGG pathway enrichment analysis involved neural activity ligand-receptor interactions, calcium signaling pathways, serotonergic synapses, taste transduction, amino acid metabolism, saliva secretion, etc. Animal experiment results showed that the food intake, mental state, and coat gloss of mice in the low-dose and high-dose groups were better than those in the positive and negative groups. The 28-day body mass growth rate of high-dose groups is higher significant than others, respectively; the tumor suppression rates of the low-dose, high-dose, and positive groups were 8.73%, 19.54%, and 47.89%, respectively.The thymus index of low-dose and high-dose groups is lower than positive group but higher than negative groups significant;the spleen index of high-dose group is lower than positive group significant.This study suggests that Fuzheng Tiaoli Decoction may mediate neural activity ligand-receptor interactions, calcium signaling pathways, serotonergic synapses, taste transduction, amino acid metabolism, salivary secretion, and other signaling pathways by affecting the expression of key target genes and improves anxiety, depression, and other negative mental states. Furthermore, it improves sleep quality, reduces fatigue, improves appetite and nutritional status, enhances immune function, improves the state of splenomegaly and thymus atrophy, enhances the immune function and inhibits tumor progression in tumor-bearing mice. The multi-target characteristics and integral action of Traditional Chinese Medicine compounds provide novel ideas for further research on the molecular mechanism of Fuzheng Tiaoli Decoction.

Key words: Fuzheng Tiaoli Decoction, anti-tumor, immunity, sub-health, network pharmacology

中图分类号: 

  • R285.5