目的: 基于网络药理学研究香青兰(Dracocephalum moldavica L.)对于脑卒中的保护作用机制。方法: 通过NCBI、CNKI找出香青兰有效成分,使用Pubchem、swiss target prediction数据库预测香青兰的有效靶点,运用GeneCards、Omim数据库搜索与脑卒中(cerebral stroke)相关靶基因,构建维恩图筛选交集基因,利用cytoscape建立药物、成分、靶点、疾病关系网络图并可视化,利用String软件构建蛋白网络互作图,利用DAVID数据库进行GO富集和KEGG分析。结果: 通过查找文献共找出香青兰有效成分23个,对应的靶点有1 682个,主要分子有NADPH氧化酶4(NOX4)、黄嘌呤氧化脱氢酶(XDH)、髓过氧化物酶(MPO)等;通过PPI拓扑分析得到核心靶点57个;GO富集分析显示涉及生物过程(biological process,BP)443个、分子功能(molecular function,MF)104个、细胞组成(cellular component,CC)66个;KEGG结果显示共涉及信号通路有143个,其中主要有癌症通路(hsa05200:pathways in cancer)、PI3K-Akt信号通路(hsa04151:PI3K-Aktsignaling pathway)、神经活性配体-受体相互作用(hsa05022:neuroactive ligand-receptor interaction)等。结论: 本研究初步揭示了香青兰可通过多种靶点、通路等治疗脑卒中,为进一步科学实验提供理论基础。
Objective: To investigate the protective effect of Dracocephalum moldavica L. on stroke based on network pharmacology. Methods: The effective components of Dracocephalum moldavica L. were searched by NCBI and CNKI. The effective targets of Dracocephalum moldavica L. were predicted by Pubchem and swiss target prediction databases. The target genes related to cerebral stroke were searched by GeneCards and Omim databases. The Venn diagram was constructed to screen the intersection genes. Cytoscape was used to establish and visualize the network diagram of drugs, components, targets and diseases. String software was used to construct the protein network interaction diagram. GO enrichment and KEGG analysis were performed using the DAVID database. Results: A total of 23 effective components of Dracocephalum moldavica L. were found by searching the literature, and there were 1682 corresponding targets. The main molecules were NADPH oxidase 4 (NOX4), xanthine dehydrogenase (XDH), myeloperoxidase (MPO), etc. Through PPI topology analysis, 57 core targets were obtained; GO enrichment analysis showed that 443 biological processes (BP), 104 molecular functions (MF) and 66 cellular components (CC) were involved. The results of KEGG showed that 143 signaling pathways were involved, including cancer pathway (hsa05200: pathways in cancer), PI3K-Akt signaling pathway (hsa04151: PI3K-Aktsignaling pathway), neuroactive ligand-receptor interaction (hsa05022: neuroactive ligand-receptor interaction) and so on. Conclusion: This study preliminarily revealed that Dracocephalum moldavica L. can treat stroke through a variety of targets and pathways, providing a theoretical basis for further scientific experiments.
[1] 莫超然,周丽丽,霍东升,等. 香青兰总黄酮对帕金森病模型小鼠黑质DAT和VMAT2蛋白表达的影响[J]. 包头医学院学报,2022,38(6):30-34,40.
[2] Jin M, Yu H, Jin X, et al. Dracocephalum moldavica L. extracts protect H9c2 cardiomyocytes against H2O2-induced apoptosis and oxidative stress[J]. Biomed Res Int, 2020,2020:8379358.
[3] 谢青,魏丹霞,顾力华,等. 桑芪首乌片对大鼠脑缺血再灌注损伤的保护作用及机制[J]. 中国老年学杂志,2022,42(15):3791-3796.
[4] 付雪琴,兰瑞,邹旭欢,等. 基于网络药理学研究丹参-川芎抗脑缺血再灌注损伤作用机制及试验验证[J]. 中国畜牧兽医,2022,49(9):3643-3654.
[5] Aprotosoaie AC, Mihai CT, Vochita G, et al. Antigenotoxic and antioxidant activities of a polyphenolic extract from European Dracocephalum moldavica L[J].Ind Crops Prod, 2016,79:248-257.
[6] Jiang JT, Yuan X, Wang T, et al. Antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. against acute ischemia/reperfusion-induced myocardial injury in isolated rat heart[J]. Cardiovasc Toxicol, 2014,14(1):74-82.
[7] Zeng C, Jiang W, Yang XY, et al. Pretreatment with total flavonoid extract from Dracocephalum moldavica L. attenuates ischemia reperfusion-induced apoptosis[J]. Sci Rep, 2018,8(1):17491.
[8] 曹文疆,信盼,赵云丽,等. 田蓟苷对动脉粥样硬化模型小鼠的改善作用及机制研究[J]. 中国药房,2022,33(1):19-25.
[9] Liu ZY, Guan C, Li CY, et al. Tilianin reduces apoptosis via the ERK/EGR1/BCL2L1 pathway in ischemia/reperfusion-induced acute kidney injury mice[J]. Front Pharmacol, 2022,13:862584.
[10] Su T, Huang CH, Yang CF, et al. Apigenin inhibits STAT3/CD36 signaling axis and reduces visceral obesity[J]. Pharmacol Res, 2020,152:104586.
[11] Yuan Y, Zhai YY, Chen JJ, et al. Kaempferol ameliorates oxygen-glucose deprivation/reoxygenation-induced neuronal ferroptosis by activating Nrf2/SLC7A11/GPX4 axis[J]. Biomolecules, 2021,11(7):923.
[12] Wang ZX, Ma J, Li XY, et al. Quercetin induces p53-independent cancer cell death through lysosome activation by the transcription factor EB and Reactive Oxygen Species-dependent ferroptosis[J]. Br J Pharmacol, 2021,178(5):1133-1148.
[13] 郭洁,方玲. 息肉切除术治疗早期结直肠癌对患者血清中CEA、IL-2、MMP-2以及MMP-9水平的影响[J]. 实用癌症杂志,2022,37(8):1339-1341,1348.
[14] 艾艳萍,丁涛. 丹参多酚酸对缺血性脑卒中再灌注损伤的保护效果分析[J]. 中西医结合心脑血管病杂志,2019,17(20):3195-3198.
[15] 马艺杰,李丹丹,陈培,等. 红花黄色素抑制P38 MAPK通路发挥保护大鼠心肌缺血-再灌注损伤作用[J]. 中药材,2022,45(8):1946-1952.
[16] 张富慧,郝静峰,张自艳,等. 菊苣酸调控p38 MAPK/NF-κB/NLRP3信号通路对缺血性脑卒中大鼠神经元凋亡及炎症反应的影响[J]. 中风与神经疾病杂志,2022,39(8):694-698.
[17] Cai H, HuangL Y, Hong R, et al.Momordica charantia exosome-like nanoparticles exert neuroprotective effects against ischemic brain injury via inhibiting matrix metalloproteinase 9 and activating the AKT/GSK3β signaling pathway[J]. Front Pharmacol, 2022,13:908830.
[18] Mo Y, Sun YY, Liu KY. Autophagy and inflammation in ischemic stroke[J]. Neural Regen Res, 2020,15(8):1388-1396.
[19] Li Y, Xiang LL, Wang C, et al. Protection against acute cerebral ischemia/reperfusion injury by Leonuri Herba Total Alkali via modulation of BDNF-TrKB-PI3K/Akt signaling pathway in rats[J]. Biomed Pharmacother, 2021,133:111021.
[20] Dehqanizadeh B, Mohammadi ZF, Kalani AHT, et al. Effect of early exercise on inflammatory parameters and apoptosis in CA1 area of the hippocampus following cerebral ischemia-reperfusion in rats[J]. Brain Res Bull, 2022,182:102-110.
[21] 吴家鹏,李学智,汪莹,等.电针结合脑内注射VEGF修复大鼠脑缺血后再灌注损伤的机制研究[J].四川大学学报(医学版),2019,50(1):34-39.
