基于体外消化和网络药理学的石榴皮提取物关键抗炎成分及其作用机制探究  

Determination of the Key Anti-Inflammatory Components in Pomegranate Peel Extract and Their Mechanisms by in Vitro Digestion and Network Pharmacology

作　　者：夏旭东 卢荣锐 蒋婷婷 袁芳 王晓彤 李滢滢 戚向阳[1] 陈秋平[1] XIA Xudong;LU Rongrui;JIANG Tingting;YUAN Fang;WANG Xiaotong;LI Yingying;QI Xiangyang;CHEN Qiuping(College of Biological and Environmental Sciences,Zhejiang Wanli University,Ningbo,Zhejiang 315100;College of Food Science and Engineering,Ocean University of China,Qingdao,Shandong 266100)

机构地区：[1]浙江万里学院生物与环境学院,浙江宁波315100 [2]中国海洋大学食品科学与工程学院,山东青岛266100

出　　处：《核农学报》2024年第7期1316-1325,共10页Journal of Nuclear Agricultural Sciences

基　　金：浙江省一流学科“生物工程”学生创新项目(CX2022024);宁波市自然科学基金(2021J177)。

摘　　要：自由基与炎症密切相关。为探究石榴皮提取物(PPE)抗炎机理,本试验采用体外模拟消化对PPE进行处理,分析主要成分和自由基清除能力变化,并结合网络药理学和分子对接技术探究PPE核心成分与炎症作用靶点的作用。结果表明,经体外消化后,PPE对羟基自由基(·OH)、2,2-联苯基-1-苦基肼基自由基(DPPH·)、2,2'-联氮-二(3-乙基-苯并噻唑-6-磺酸)二铵盐自由基(ABTS·^(+))的清除能力均较消化前有不同程度提高,其中·OH的半清除浓度(IC_(50·OH))由186.79μg·mL^(-1)下降至119.52μg·mL^(-1),清除效果提高36.01%。通过液质联用技术共分析鉴定出19种化合物,其中6-O-没食子酰葡萄糖苷、表没食子儿茶素、鞣花酸和山奈酚含量在消化后显著提高。网络药理学分析表明,PPE抗炎关键成分主要作用于白介素-1B(IL1B)、白介素-6(IL6)、肿瘤坏死因子(TNF)、基质金属蛋白酶9(MMP9)、前列腺素内过氧化物合酶2(PTGS2)、核因子-κB(NF-κB)、白介素-8(IL8)等7个炎症靶点,与NF-κB炎症通路密切相关。进一步的分子对接结果显示,柯里拉京、鞣花酸、异槲皮苷与PTGS2结合最佳,而山奈酚与MMP9结合最佳。本研究结果可为PPE在抗炎产品开发中的应用提供新思路。Free radicals are intricately linked to the inflammatory process.This study was to investigate the anti-inflammatory mechanism of pomegranate peel extract(PPE)using in vitro digestion simulations.By analyzing alterations in its components and capacity to scavenge free radicals,the key components of PPE were discovered,and their inflammatory targets were investigated through network pharmacology and molecular docking.After in vitro digestion,the scavenging ability of PPE against hydroxyl radical(·OH)、2,2-diphenyl-1-picrylhydrazyl radical(DPPH·)、2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate)radical(ABTS·^(+))was improved.The IC_(50·OH) value decreased from 186.79 to 119.52 g·mL^(-1),and the scavenging efficiency increased by 36.01%.Through UPLC-Q-TOF MS/MS analysis,19 compounds were identified,including 6-O-glucoside,epigallocatechin,ellagic acid and kaempferol,all of which increased significantly after digestion.A network pharmacology analysis of PPE’s key anti-inflammatory components showed that PPE mainly targeted 7 inflammatory targets,including IL1B,IL6,TNF,MMP9,PTGS2,NF-κB and IL8.These components exhibited deep connections with the NF-κB inflammatory pathway.Molecular docking results showed that corilagin,ellagic acid and isoquercitrin exhibited the highest affinity for PTGS2,whereas kaempferol demonstrated the strongest binding to MMP9.This study could provide potential avenues for developing and applying of PPE in the formulation of anti-inflammatory products.

关 键 词：石榴皮 抗炎 体外消化 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]