目的: 利用网络药理学研究蓝盆花总黄酮活性成分的抗非酒精性脂肪性肝炎作用机制。方法: :基于TCMSP数据库及文献报道获取蓝盆花总黄酮主要活性成分。依据反向药效团匹配方法采用Swiss Target Prediction服务器预测其活性成分靶标,并通过Genecards、OMIM、Disgenet等数据库筛选出改善非酒精性脂肪性肝炎的靶标。取药物靶点与疾病靶点共同作用的潜在靶点制作韦恩图,使用Cytoscape软件,构建“活性成分-靶点”网络图,利用STRING平台构建蛋白互作网络,利用DAVID数据库与ClueGO插件进行GO富集分析和KEGG通路分析。结果: 共筛选得到蓝盆花总黄酮的活性成分43个及靶点439个,网络中主要活性成分为芒柄花苷、莰菲醇-3-O-芸香糖苷、异鼠李素、槲皮素、木犀草素、淫香叶木素等,蛋白互作网络中关键靶点为TNF、AKT1、TP53、VEGFA、IL1B等。GO富集分析共涉及到生物过程503个,细胞组分54个,分子功能120个,KEGG通路富集分析筛选前20条相关通路,主要作用于VEGF信号通路、PPAR信号通路、雌激素信号通路等。结论: 蓝盆花的黄酮成分可通过多靶标、多通路发挥治疗非酒精性脂肪性肝炎的作用,该结果为深入研究蓝盆花在抗非酒精性脂肪性肝炎等领域的作用提供了科学依据。
Objective: To study the anti-nonalcoholic steatohepatitis mechanism of total flavonoids from Scabiosa comosa by network pharmacology. Methods: Based on the TCMSP database and literature reports, the main active components of total flavonoids from Scabiosa comosa were obtained. The Swiss Target Prediction server was used to predict the target of its active ingredients according to the reverse pharmacophore matching method, and the targets for improving NASH were screened out through databases such as Genecards, OMIM and Disgenet. The potential targets of drug targets and disease targets were used to make the Venn diagram. The Cytoscape software was used to construct the ' active ingredient-target ' network diagram. The STRING platform was used to construct the protein interaction network. The DAVID database and ClueGO plug-in were used for GO enrichment analysis and KEGG pathway analysis. Results: A total of 43 active components and 439 targets of total flavonoids were screened. The main active components in the network were ononin, camphene -3-O- rutinoside, isorhamnetin, quercetin, luteolin, eupatorium odoratum, etc. The key targets in the protein interaction network were TNF, AKT1, TP53, VEGFA, IL1B, etc. GO enrichment analysis involved 503 biological processes, 54 cellular components and 120 molecular functions. KEGG pathway enrichment analysis screened the top 20 related pathways, mainly acting on VEGF signaling pathway, PPAR signaling pathway, estrogen signaling pathway and so on. Conclusion: The flavonoid components from Scabiosa comosa can play a role in the treatment of nonalcoholic steatohepatitis through multiple targets and multiple pathways. The results provide a scientific basis for further study of the role of Scabiosa comosa in the field of anti-nonalcoholic steatohepatitis.
[1] 苏达毕力格, 何陈林, 朝格巴达拉夫, 等. 蓝盆花属植物化学成分及药理作用研究进展[J]. 中国现代应用药学, 2023, 40(8): 1136-1146.
[2] 内蒙古自治区革命委员会卫生局. 内蒙古中草药[M]. 呼和浩特: 内蒙古人民出版社, 1972: 158.
[3] 国家中医药管理局. 中华本草·第七卷[M]. 上海: 上海科学技术出版社, 1999: 6637.
[4] 张春艳, 金蓉, 颜羽昕, 等. 基于药效学和网络药理方法探讨蓝盆花抗肝纤维化的作用机制[J]. 中国中药杂志, 2022, 47(13): 3609-3618.
[5] 陈倩莉, 黎巍威, 叶晖, 等. 基于网络药理学探究莪术油治疗胃癌的潜在活性成分及作用机制[J]. 中国中西医结合消化杂志, 2021, 29(5): 313-320.
[6] 吴青华, 李冰涛, 朱水兰, 等. 蒙古族药芯芭治疗2型糖尿病的网络药理学研究[J]. 中国中药杂志, 2020, 45(08).
[7] UniProt Consortium. UniProt: a worldwide hub of protein knowledge[J]. Nucleic Acids Res, 2019; 47(D1): D506-D515.
[8] Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources[J]. Nat Protoc, 2009, 4(1): 44-57.
[9] Bindea G, Mlecnik B, Hackl H, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks[J]. Bioinformatics, 2009, 25(8): 1091-1093.
[10] 毛继祖, 马世林. 月王药诊[M]. 上海: 上海科学技术出版社, 2012: 40.
[11] 孟根斯立木, 梁洁, 金蓉, 等. 蒙医药治疗肝病的研究进展[J]. 中国民族医药杂志, 2018, 24(8): 60-63.
[12] Raza S. Current treatment paradigms and emerging therapies for NAFLD/NASH[J]. Front Biosci, 2021, 26(2): 206-237.
[13] 蔡淑珍, 李建良, 陈圆, 等. 基于网络药理学的荜茇降血脂作用机制研究[J]. 医药导报, 2019, 38(11): 1398-1402.
[14] Kuipers EN, Dam ADV, Held NM, et al. Quercetin lowers plasma triglycerides accompanied by white adipose tissue browning in diet-induced obese mice[J]. Int J Mol Sci, 2018, 19(6): 1786.
[15] Moon J, Do HJ, Kim OY, et al. Antiobesity effects of quercetin-rich onion peel extract on the differentiation of 3T3-L1 preadipocytes and the adipogenesis in high fat-fed rats[J]. Food Chem Toxicol, 2013, 58: 347-354.
[16] Alkhalidy H, Moore W, Zhang YL, et al. Small molecule kaempferol promotes insulin sensitivity and preserved pancreatic β-cell mass in middle-aged obese diabetic mice[J]. J Diabetes Res, 2015, 2015: 532984.
[17] 黄建. 异鼠李素对扑热息痛诱导小鼠药物性肝损伤的保护作用及其机制研究[D]. 呼和浩特: 内蒙古农业大学, 2020.
[18] 申玲玲, 朱春胜, 许石钟. 基于网络药理学的菊苣抗高脂血症作用机制研究[J]. 现代药物与临床, 2020, 35(12): 2300-2306.
[19] 龚勇珍, 孙少卫, 廖端芳. 细胞炎症反应与脂质代谢的相互作用及调节[J]. 中国动脉硬化杂志, 2017, 25(6): 623-629.
[20] Wang LT, Huang ZQ, Huang WJ, et al. Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress[J]. Sci Rep, 2017, 8: 45917.
[21] 李梦华. 新型PPARs-α/γ/δ和GPR40四重激动剂RLA8对非酒精性脂肪性肝炎的疗效及作用机制[D]. 青岛: 山东大学, 2019.
[22] Zengin A, Nguyen AD, Wong IPL, et al. Neuropeptide Y mediates the short-term hypometabolic effect of estrogen deficiency in mice[J]. Int J Obes (Lond), 2013, 37(3): 390-398.
[23] 马柳安, 邱惠玲, 李荔, 等. miRNA通过PPAR和AMPK/SREBPs信号通路调控脂质代谢[J]. 生命的化学, 2017, 37(6): 1017-1029.
