基于代謝組學(xué)及網(wǎng)絡(luò)藥理學(xué)分析不同品種芡實(shí)中活性成分及其對(duì)人糖尿病的作用

摘要： 通過代謝組學(xué)、網(wǎng)絡(luò)藥理學(xué)及分子對(duì)接技術(shù)分析不同芡實(shí)品種中的活性成分及其對(duì)糖尿病的作用。使用四極桿飛行時(shí)間液質(zhì)聯(lián)用系統(tǒng)（LC-QTOF-MS）、Metaboanalyst（https：//www.metaboanalyst.ca/）和TBtools軟件對(duì)芡實(shí)成分進(jìn)行檢測(cè)和分析；通過PubChem篩選出芡實(shí)中具有生物活性的成分；使用Swiss預(yù)測(cè)芡實(shí)成分靶點(diǎn)，通過多種數(shù)據(jù)庫檢索疾病靶點(diǎn)取并集；繪制蛋白質(zhì)互作（PPI）網(wǎng)絡(luò)查找主要成分及核心靶點(diǎn)；對(duì)交集靶點(diǎn)進(jìn)行GO富集分析和KEGG富集分析；最后通過分子對(duì)接技術(shù)進(jìn)行驗(yàn)證。結(jié)果表明，蘇芡和刺芡中有153種在含量方面具有顯著差異的成分；從蘇芡中篩選出12種具有緩解糖尿病及其并發(fā)癥效果的成分以及578個(gè)潛在靶點(diǎn)，從刺芡中篩選出3種具有緩解糖尿病及其并發(fā)癥效果的成分及226個(gè)潛在靶點(diǎn)；GO富集和KEGG富集分析結(jié)果顯示，蘇芡中的靶點(diǎn)主要富集在糖尿病性心肌病、胰島素抵抗、糖尿病并發(fā)癥中的高級(jí)糖基化終末產(chǎn)物-受體信號(hào)通路，刺芡中的靶點(diǎn)主要富集在癌癥的發(fā)病途徑、脂肪細(xì)胞脂解的調(diào)控、磷酸腺苷活化蛋白激酶信號(hào)通路；分子對(duì)接分析結(jié)果顯示，篩選出的成分均結(jié)合在靶點(diǎn)蛋白質(zhì)的凹陷處，結(jié)合自由能均為負(fù)值，分子對(duì)接構(gòu)象穩(wěn)定。說明，蘇芡在緩解糖尿病及其并發(fā)癥等方面較刺芡具有更好的效果。

關(guān)鍵詞： 芡實(shí)；糖尿病；代謝組學(xué)；網(wǎng)路藥理學(xué)；分子對(duì)接

中圖分類號(hào)： R285;S645.9 文獻(xiàn)標(biāo)識(shí)碼： A 文章編號(hào)： 1000-4440（2024）11-2163-14

Effects of active components in different varieties of Euryale ferox on human diabetes based on metabolomics and network pharmacology

ZHANG Qingqiang^1，2， MA Jiajia³， ZHU Hequan²， LI Yong⁴， LI Hongling⁵， LIU Huan²， CAI Weirong¹， LI Chunyang²

（1.College of Biological and Food Engineering， Anhui Polytechnic University， Wuhu 241000， China;2.Institute of Agroproduct Processing， Jiangsu Academy of Agricultural Sciences， Nanjing 210014， China;3.Taihu Research Institute of Agricultural Sciences， Suzhou 215000， China;4.Institute of Agricultural Resources and Environment， Jiangsu Academy of Agricultural Sciences， Nanjing 210014， China;5.College of Food Science and Light Industry， Nanjing Tech University， Nanjing 211816， China）

Abstract： This study aims to elucidate the active ingredient differences in Euryale ferox and the alleviation of diabetes among different varieties， known as South Euryale and North Euryale， using metabolomics， network pharmacology， and molecular docking techniques. Liquid chromatography-quadrupole time of flight-mass spectrometry （LC-QTOF-MS）， Metaboanalyst（https：//www.metaboanalyst.ca/）， and TBtools were used for the detection and analysis of components in E. ferox. Bioactive components in E. ferox were screened through PubChem. Swiss was used to predict the targets of E. ferox components， and disease targets were searched from multiple databases and combined. Protein-protein interaction （PPI） networks were constructed to identify major components and core targets. GO analysis and KEGG analysis were conducted on the intersected targets. Finally， molecular docking models were used for validation. The results showed that 153 components with significant differences in the content were found between South Euryale and North Euryale. Twelve components with the potential to alleviate diabetes and its complications， along with 578 potential targets， were identified in South Euryale， while three components and 226 potential targets were identified in North Euryale. GO and KEGG enrichment analysis revealed that the targets in South Euryale were mainly enriched in the pathogenesis of diabetic cardiomyopathy， insulin resistance， and the advanced glycation end products-receptor of advanced glycation endproducts （AGE-RAGE） signaling pathway in diabetic complications， while the targets in North Euryale were primarily enriched in the pathogenesis of cancer， regulation of adipocyte lipolysis， and the adenosine 5’-monophosphate （AMP）-activated protein kinase （AMPK） signaling pathway. Molecular docking results showed that the screened components combined to the depressed sites of target proteins， with negative binding free energy and stable molecular docking conformations. It can be concluded that South Euryale exhibited better effects in alleviating diabetes and its complications compared to North Euryale.

Key words： Euryale ferox;diabetes;metabolomics;network pharmacology;molecular docking

芡實(shí)（Euryale ferox Salish.）俗稱雞頭米，為睡蓮科芡屬一年水生草本植物，屬藥食同源作物。芡實(shí)主要分為2類：一類是刺芡，也叫北芡或者野芡，在福建省、浙江省、安徽省及江蘇省北部等地種植，籽粒殼薄、粒小、粳性，呈白色；……