基于液质联用和网络药理学探讨天花粉防治糖尿病的作用机制

The mechanism of Trichosanthis Radix in preventing and treating diabetes:a study based on liquid chromatography-mass spectrometry and network pharmacology

目的 通过超高效液相色谱联用质谱技术(UPLC-MS)分析中药天花粉中的化合物成分,结合网络药理学和分子对接技术探究天花粉防治糖尿病的作用机制。方法 应用液质联用技术解析天花粉水提物,获取天花粉成分及结构并筛选得到潜在活性成分。通过Swiss Target Prediction数据库对潜在活性成分进行靶点预测,从GeneCards数据库收集糖尿病相关疾病靶点并取二者交集靶点。应用STRING网站和Cytoscape软件构建蛋白质互作网络并筛选得到核心靶点。将核心靶点导入Metascape网站进行GO和KEGG分析。结果 液质联用解析得到天花粉15种药物成分,筛选出Cucurbitacin D(葫芦素D)等6种潜在活性成分,分析得61个天花粉防治糖尿病靶点。GO富集分析主要包括脂肪酸代谢、单羧酸代谢、类固醇羟化酶活性等脂质代谢和氧化应激相关进程。KEGG富集分析主要涉及胰岛素抵抗、内分泌抵抗、糖尿病并发症的AGE-RAGE信号通路等糖尿病防治密切相关的通路。分子对接发现天花粉可能通过Cucurbitacin D作用STAT3、MAPK14、PIK3CA等关键靶点实现改善糖尿病的效果。结论 天花粉具有潜在防治糖尿病的功效,其机制可能是通过Cucurbitacin D等活性成分改善胰岛素抵抗及内分泌抵抗,调控AGE-RAGE等信号通路,从而起到防治糖尿病的作用。

Objective To use Ultra-Performance Liquid Chromatography-Mass Spectrometry(UPLC-MS)technology to analyze the components of Trichosanthis Radix(Tianhuafen),combined with techniques in network pharmacology and molecular docking to explore the mechanism of Tianhuafen in preventing and treating diabetes.Methods Used UPLC-MS technology,we analyzed the water extract of Tianhuafen,obtained its components and structures,and screened for potential active ingredients.The Swiss Target Prediction database was employed for target prediction of potential active ingredients.We collected diabetes-related disease targets from the GeneCards database and took the intersection of the two sets of targets.Subsequently,we used the STRING website and Cytoscape software to construct a protein-protein interaction network and screened for core targets.These core targets were then imported into the Metascape website for GO and KEGG analysis.Results UPLC-MS analysis identified 15 components of Tianhuafen,and 6 potential active ingredients were screened,including Cucurbitacin D.Analysis revealed 61 targets for Tianhuafen in preventing and treating diabetes.GO enrichment analysis mainly involved processes related to lipid metabolism and oxidative stress,such as fatty acid metabolism,monocarboxylic acid metabolism,and steroid hydroxylase activity.KEGG enrichment analysis primarily encompassed pathways closely related to diabetes prevention and treatment,including insulin resistance,endocrine resistance,and the AGE-RAGE signaling pathway in diabetic complications.Molecular docking revealed that Tianhuafen may improve diabetes by targeting key points such as STAT3,MAPK14,and PIK3CA through Cucurbitacin D.Conclusion Trichosanthis Radix has the potential effect of preventing and treating diabetes,and its mechanism may be to improve insulin resistance and endocrine resistance through active ingredients such as Cucubitacin D,regulate AGE-RAGE and other signal pathways,thus playing a role in preventing and treating diabetes.