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基于体外实验和网络药理学探讨紫苏粕多肽抗氧化应激的作用机制

Exploration of mechanism of anti-oxidative stress of perilla meal peptides based on in vitro experiments and network pharmacology
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摘要 利用体外实验和网络药理学的方法对紫苏粕多肽抗氧化应激的物质基础和作用机制进行研究。首先对紫苏粕碱性蛋白酶酶解液进行超滤分级,以得率和抗氧化活性为指标,筛选出级分UF-4(<1 kDa),考察其对H_(2)O_(2)诱导的4T1细胞氧化应激模型的保护作用,发现UF-4可剂量性显著降低胞外乳酸脱氢酶活性和胞内丙二醛含量,显著提高胞内谷胱甘肽的含量及超氧化物歧化酶、过氧化氢酶活性,说明UF-4具有一定的抗氧化作用。在此基础上,运用网络药理学的方法,从UF-4中筛选出潜在活性物质18种,其对应靶点中与抗氧化作用相关的有176个,通过蛋白互作分析得到6个核心靶点,GO和KEGG富集分析表明UF-4通过多靶点、多途径的方式发挥抗氧化应激作用,主要涉及细胞凋亡、脂质与动脉粥样硬化、钙调节、炎症等生物学过程。分子对接进一步验证了18种潜在活性成分与核心靶点间存在较强的相互作用。总之,该研究初步表明UF-4抗氧化应激过程中多组分、多靶点、多通路的作用特点,为后期紫苏粕多肽抗氧化作用的研究与应用提供理论依据及参考。 This study used in vitro experiments and network pharmacology to study the material basis and action mechanism of perilla meal polypeptide antioxidant stress.First,the alkaline protease hydrolysate of Perilla frutescens meal was classified by ultrafiltration,and the fraction UF-4(<1 kDa)was selected based on the yield and antioxidant activity,and its protective effect on the oxidative stress model of 4T1 cells induced by H_(2)O_(2)was investigated.It was found that UF-4 could significantly reduce the activity of extracellular lactate dehydrogenase(LDH)and the content of intracellular malondialdehyde(MDA),significantly increase the content of intracellular antioxidant factor glutathione(GSH)and the activity of antioxidant enzymes superoxide dismutase(SOD)and catalase(CAT),indicating that UF-4 had a certain antioxidant effect.On this basis,18 kinds of potential active substances were screened from UF-4 by network pharmacology,176 of which were related to antioxidation.Six core targets were obtained through protein interaction analysis.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis showed that UF-4 exerted antioxidant stress through multiple targets and pathways,mainly involving biological processes such as apoptosis,lipid and atherosclerosis,calcium regulation,inflammation,etc.Molecular docking further verified the strong interaction between 18 potentially active ingredients and core targets.In conclusion,this study preliminarily showed the characteristics of multi-component,multi-target,and multi-path action in the process of UF-4 antioxidant stress,and provided a theoretical basis and reference for the research and application of the antioxidant effect of perilla meal peptides in the later stage.
作者 张红玉 李会珍 张志军 赵亚娜 侯天宇 李河 陈林 ZHANG Hongyu;LI Huizhen;ZHANG Zhijun;ZHAO Yana;HOU Tianyu;LI He;CHEN Lin(School of Chemistry and Chemical Engineering,Central North University,Taiyuan 030051,China;Jinzhong Industrial Technology Innovation Research Institute of Central North University,Jinzhong 030600,China)
出处 《食品与发酵工业》 CAS CSCD 北大核心 2024年第10期149-159,共11页 Food and Fermentation Industries
基金 山西省重点研发计划项目特优农业技术创新专项(2022ZDYF123) 山西省基础研究计划青年项目(202203021222032) 晋中市重点研发计划(Y212006) 山西省研究生创新项目(2022Y614)。
关键词 紫苏粕多肽 氧化应激 网络药理学 作用机制 分子对接 perilla meal polypeptide oxidative stress network pharmacology mechanism of action molecular docking
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