文献类型：期刊文献

中文题名：基于网络药理学和分子对接探究罗汉果提取物抗炎作用机制

英文题名：To Explore Anti-Inflammatory Mechanism of Momordica grosvenori Extract Based on Network Pharmacology and Molecular Docking

作者：张进[1];武慧宁[1];赵林露[1];郭梦如[1];何洁仪[1];刘晓曦[1]

机构：[1]广东海洋大学滨海农业学院动物医学系,湛江524000

年份：2025

卷号：37

期号：2

起止页码：1325

中文期刊名：动物营养学报

外文期刊名：CHINESE JOURNAL OF ANIMAL NUTRITION

收录：北大核心2023、、北大核心

基金：国家自然科学基金青年科学基金(31902314);广东海洋大学南海学者计划(002029002005)。

语种：中文

中文关键词：罗汉果提取物;网络药理学;分子对接;炎症;作用机制

外文关键词：Siraitia grosvenorii extract;network pharmacology;molecular docking;inflammation;mechanism of action

中文摘要：本试验旨在探究罗汉果提取物对动物炎症的调控作用及潜在分子机制。首先进行小鼠试验,将18只C57/BL6小鼠随机分为3组,每组6只。CON组和LPS组饲喂正常饲粮,SGE组在饲喂正常饲粮的基础上灌胃罗汉果提取物(100 mg/kg BW)14 d;在第15天,CON组小鼠不做处理,LPS组和SGE组小鼠腹腔注射脂多糖(LPS)(5 mg/kg BW)建立炎症模型。LPS注射6 h后处死全部小鼠采样,检测小鼠血清中免疫球蛋白G(IgG)和免疫球蛋白M(IgM)含量以及空肠和脾脏中炎性因子的表达情况。接着,通过中药系统药理学与分析平台数据库(TCMSP)筛选罗汉果提取物的主要有效成分及作用靶点,通过GeneCards、DisGeNET和OMIM数据库收集炎症的靶点;采用靶点数据构建蛋白质-蛋白质相互作用(PPI)网络图,并进行GO功能和KEGG通路富集分析。最后,通过PyMOL和AutodockTools软件将度值排名前5的核心靶点与有效成分进行分子对接,验证关键有效成分与核心靶点的结合活性。结果表明:1)灌胃罗汉果提取物显著或极显著升高了LPS诱导的炎症模型小鼠血清中IgG和IgM含量(P<0.05或P<0.01),显著或极显著降低了空肠中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)和脾脏中白细胞介素-6(IL-6)的mRNA表达量(P<0.05或P<0.01),并显著增加了脾脏中抗炎因子白细胞介素-10(IL-10)的mRNA表达量(P<0.05)。2)网络药理学分析显示,罗汉果提取物抗炎有效成分有3个:山奈酚、川芎哚和酒渣碱;筛选出度值前5的核心靶点为丝/苏氨酸蛋白激酶1(AKT1)、半胱氨酸天冬氨酸蛋白酶3(CASP3)、表皮生长因子受体(EGFR)、基质金属蛋白酶9(MMP9)和前列腺素内过氧化物合酶2(PTGS2);GO功能富集分析获得了324个生物过程、54个细胞组分以及99个分子功能;KEGG通路富集分析得到105条相关信号通路,主要涉及磷脂酰肌醇3激酶-蛋白激酶B(PI3K-AKT)信号通路、白细胞介素-17(IL-17)信号通路和肿瘤坏死因子(TNF)信号通路。3)分子对接结果显示,核心靶点与有效成分结合自由能均小于0 kJ/mol,表明罗汉果提取物有效成分与核心靶点能自发结合。综上所述,本研究筛选出了罗汉果提取物发挥抗炎作用的主要活性成分及作用靶点,并探究了其分子机制,可为后续罗汉果提取物的应用与开发提供理论依据。

外文摘要：The objective of this study was to examine the regulatory impact and potential molecular mechanism of Siraitia grosvenorii extract on inflammation in animals.First,the mice test was carried.Eighteen C57/BL6 mice were divided into 3 groups,with 6 mice in each group.Mice in CON group and LPS group were fed a normal diet,and mice in PSE group were given Siraitia grosvenorii extract(100 mg/kg BW)intragastrically on the basis of feeding the normal diet for 14 days.On the 15th day,mice in the CON group were not treated,and those in the LPS group and PSE group were injected intraperitoneally with LPS(5 mg/kg BW)to establish an inflammatory model.Six hours after LPS injection,all mice were sacrificed for sampling,and the contents of immunoglobulin G(IgG)and immunoglobulin M(IgM)in serum and the expression of inflammatory factors in jejunum and spleen were determined.Subsequently,the principal effective constituents and targets of Siraitia grosvenorii extract were identified through a screening process conducted using the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform Database(TCMSP).Additionally,the targets associated with inflammation were collated through GeneCards,DisGeNET and OMIM databases.A protein-protein interaction(PPI)network diagram was constructed using the target data,and GO function and KEGG pathway enrichment analysis were performed.Subsequently,PyMOL and AutodockTools software were employed to undertake molecular docking between the five most prominent core targets and the effective constituents,thereby corroborating the binding efficacy of the pivotal effective constituents with the core targets.The results showed as follows:1)the administration of Siraitia grosvenorii extract could significantly or extremely significantly increase the contents of serum IgG and IgM of mice with LPS-induced inflammation(P<0.05 or P<0.01).Furthermore,it could significantly or extremely significantly reduce the mRNA expression levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)in jejunum and interleukin-6(IL-6)in spleen(P<0.05 or P<0.01),and it also could significantly increase the mRNA expression levels of interleukin-10(IL-10)in spleen(P<0.05).2)A network pharmacological analysis revealed the presence of three anti-inflammatory effective constituents in Siraitia grosvenorii extract,namely kaempferol,chuanxiongole and rosmarinic acid.The top five core targets were identified as serine threonine protein kinase 1(AKT1),cysteine aspartic protease 3(CASP3),epidermal growth factor receptor(EGFR),matrix metalloproteinase 9(MMP9)and prostaglandin endoperoxide synthase 2(PTGS2).A total of 324 biological processes,54 cell components and 99 molecular functions were identified through the GO functional enrichment analysis.A total of 105 related signaling pathways were identified through the KEGG pathway enrichment analysis,with the phosphatidylinositol 3 kinase-protein kinase B(PI3K-Akt)signaling pathway,interleukin-17(IL-17)signaling pathway and tumor necrosis factor(TNF)signaling pathway representing the most prominent among them.3)The results of the molecular docking demonstrated that the binding free energy of the core targets and the effective constituents was less than 0 kJ/mol,indicating that the Siraitia grosvenorii extract was capable of spontaneous binding to the core target.In summary,this study screens the effective constituents and targets of Siraitia grosvenorii extract in the context of inflammation,and investigates its underlying molecular mechanisms.This research provides a theoretical foundation for the subsequent application and advancement of Siraitia grosvenorii extract.