Article(id=1320166457112113698, tenantId=1146029695717560320, journalId=1260987677001138203, issueId=1320166220377215955, articleNumber=null, orderNo=null, doi=10.13386/j.issn1002-0306.2025060021, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1749052800000, receivedDateStr=2025-06-05, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1792681810881, onlineDateStr=2026-10-22, pubDate=1780243200000, pubDateStr=2026-06-01, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792681810881, onlineIssueDateStr=2026-10-22, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792681810881, creator=13701087609, updateTime=1792681810881, updator=13701087609, issue=Issue{id=1320166220377215955, tenantId=1146029695717560320, journalId=1260987677001138203, year='2026', volume='47', issue='11', pageStart='1', pageEnd='514', issueExtLink='null', onlineDate='null', pubDate='1780243200000', pubDateStr='2026-06-01', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792681754440, creator='13701087609', updateTime=1792681754440, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=426, endPage=432, ext={EN=ArticleExt(id=1320166457292468771, articleId=1320166457112113698, tenantId=1146029695717560320, journalId=1260987677001138203, language=EN, title=Evaluation of the Effect of Ferulic Acid in Alleviating the Sensitization of Parvalbumin, columnId=1261343846965830077, journalTitle=Science and Technology of Food Industry, columnName=Nutrition and Healthcare, runingTitle=null, highlight=null, articleAbstract=

Network pharmacology and Swiss Target Prediction were used to retrieve the associated targets of ferulic acid in relation to food hypersensitivity in this paper, and the key targets and action pathways of ferulic acid in alleviating food allergies were identified by conducting enrichment prediction of GO and KEGG pathways. The binding ability of ferulic acid to these key targets was further validated via molecular docking technology. Finally, the effects of ferulic acid on degranulation of KU812 cells, allergic symptoms and serum specific antibody contents of the sensitized mice by parvalbumin were investigated at the cellular and animal levels, thereby evaluating the efficacy of ferulic acid in alleviating parvalbumin sensitization. The results indicated that 46 crucial targets of ferulic acid for alleviating food allergy were identified. The relevant targets were significantly enriched in pathways including Th17, JAK-STAT, and inflammatory bowel disease. Ferulic acid exhibited favorable binding activity with target proteins NAKB1, STAT3, IL2, and JAK2, and the binding energy all lower than −4.0 kJ/mol. Meanwhile, ferulic acid significantly reduced the release ability of histamine and interleukin-6 in sensitized KU812 cells, mitigated allergic symptoms, decreased the contents of specific antibodies and allergic mediators in the serum of parvalbumin-induced sensitized mice, thereby alleviating their allergic responses. Therefore, ferulic acid has the potential to alleviate food allergies, and the research results provide a theoretical foundation for the development of anti-allergy drugs to treat food allergies.

, authors=Kai ZHANG1, Shu ZENG1, Fei WEI1, Jun LIU2, *, authorsList=Kai ZHANG, Shu ZENG, Fei WEI, Jun LIU, authorCompany=null, correspAuthors=Jun LIU, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright © 2026 Science and Technology of Food Industry. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1320166459553198646, articleId=1320166457112113698, tenantId=1146029695717560320, journalId=1260987677001138203, language=CN, title=阿魏酸缓解小清蛋白致敏性的效果评价, columnId=1261343850979779009, journalTitle=食品工业科技, columnName=营养与保健, runingTitle=null, highlight=null, articleAbstract=

本文采用网络药理学、Swiss Target Prediction等数据库获取阿魏酸和食物过敏反应的关联靶点,基于GO及KEGG通路富集预测阿魏酸缓解食物过敏的关键靶点及作用途径,通过分子对接技术进一步验证阿魏酸与关键靶点的结合能力;最后在细胞和动物水平上探究阿魏酸对KU812细胞脱颗粒、小清蛋白致敏小鼠过敏症状和血清特异抗体含量的影响,评价阿魏酸对小清蛋白引起食物过敏反应的缓解效果。结果表明:筛选出阿魏酸缓解食物过敏的重要潜在靶点有46个,关联靶点富集在Th17、JAK-STAT和炎症性肠病等通路,阿魏酸与NAKB1、STAT3、IL2、JAK2靶蛋白有较好的结合活性,结合能均低于−4.0 kJ/mol;同时阿魏酸可以降低敏化KU812细胞释放组胺和IL-6的含量,减轻小清蛋白诱导的致敏小鼠过敏症状以及显著降低血清中特异抗体含量,缓解其过敏反应。阿魏酸具有潜在缓解食物过敏的能力,研究结果为研发抗过敏类药物治疗食物过敏提供理论依据。

, authors=章开1, 曾姝1, 魏斐1, 刘俊2, *, authorsList=章开, 曾姝, 魏斐, 刘俊, authorCompany=null, correspAuthors=刘俊, authorNote=

章开(1991−)(ORCID:0009−0002−4908−4893),女,博士研究生,研究方向:药食组分相互作用,E-mail:

, correspAuthorsNote=
刘俊(1989−)(ORCID:0000−0002−8570−5741),男,博士,副教授,研究方向:食品营养组分相互作用,E-mail:。
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注:不同小写字母表示差异显著(P<0.05),图8~图9同。

, figureFileSmall=Nr+hGrAKv8eu5w4gWmIiDQ==, figureFileBig=OamPhVleaoFdCLiLftHGZw==, tableContent=null), ArticleFig(id=1320167169200075097, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320166457112113698, language=EN, label=Fig.8, caption=Allergic symptom score (A), temperature changes (B), spleen index (C) and thymus index (D) in mice, figureFileSmall=3gj/A7i2t0riXORtzj6cXg==, figureFileBig=UbsREaJNPgLNFtUvJ5DcMg==, tableContent=null), ArticleFig(id=1320167169262989658, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320166457112113698, language=CN, label=图8, caption=小鼠过敏症状评分(A)、体温变化(B)、脾脏(C)和胸腺(D)指数, figureFileSmall=3gj/A7i2t0riXORtzj6cXg==, figureFileBig=UbsREaJNPgLNFtUvJ5DcMg==, tableContent=null), ArticleFig(id=1320167169321709915, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320166457112113698, language=EN, label=Fig.9, caption=Mouse serum-specific IgE (A) and IgG (B) content, figureFileSmall=Y/cjuApVEO5Yl79pDPA3xg==, figureFileBig=L0czZM+K/gtwemSLkAYuaA==, tableContent=null), ArticleFig(id=1320167169388818780, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320166457112113698, language=CN, label=图9, caption=小鼠血清特异性IgE(A)和IgG(B)含量, figureFileSmall=Y/cjuApVEO5Yl79pDPA3xg==, figureFileBig=L0czZM+K/gtwemSLkAYuaA==, tableContent=null), ArticleFig(id=1320167169464316253, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320166457112113698, language=EN, label=Table 1, caption=

Molecular docking results for ferulic acid and protein targets

, figureFileSmall=null, figureFileBig=null, tableContent=
蛋白靶点结合能力(kJ/mol)氢键数量关键氨基酸残基
NFKB1(1mdi)−4.92Gln63、Ser67
STAT3(5u5s)−5.91Asn86
IL2(11irl)−5.23Asn33、Lys76、Phe78
JAK2(3e62)−6.71Leu932
), ArticleFig(id=1320167169535619422, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320166457112113698, language=CN, label=表1, caption=

阿魏酸与蛋白靶点分子对接结果

, figureFileSmall=null, figureFileBig=null, tableContent=
蛋白靶点结合能力(kJ/mol)氢键数量关键氨基酸残基
NFKB1(1mdi)−4.92Gln63、Ser67
STAT3(5u5s)−5.91Asn86
IL2(11irl)−5.23Asn33、Lys76、Phe78
JAK2(3e62)−6.71Leu932
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阿魏酸缓解小清蛋白致敏性的效果评价
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章开 1 , 曾姝 1 , 魏斐 1 , 刘俊 2, *
食品工业科技 | 营养与保健 2026,47(11): 426-432
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食品工业科技 |营养与保健 2026 , 47 (11) : 426 -432
阿魏酸缓解小清蛋白致敏性的效果评价
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章开1 , 曾姝1, 魏斐1, 刘俊2, *
作者信息
  • 1江西省肿瘤医院药学部,江西南昌 330029
  • 2江西师范大学生命科学学院,江西南昌 330022
通讯作者:
刘俊(1989−)(ORCID:0000−0002−8570−5741),男,博士,副教授,研究方向:食品营养组分相互作用,E-mail:。
作者简介:

章开(1991−)(ORCID:0009−0002−4908−4893),女,博士研究生,研究方向:药食组分相互作用,E-mail:

Evaluation of the Effect of Ferulic Acid in Alleviating the Sensitization of Parvalbumin
Kai ZHANG1 , Shu ZENG1, Fei WEI1, Jun LIU2, *
Affiliations
  • 1Department of Pharmacy, Jiangxi Cancer Hospital, Nanchang 330029, China
  • 2College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China
出版时间: 2026-06-01 doi: 10.13386/j.issn1002-0306.2025060021
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本文采用网络药理学、Swiss Target Prediction等数据库获取阿魏酸和食物过敏反应的关联靶点,基于GO及KEGG通路富集预测阿魏酸缓解食物过敏的关键靶点及作用途径,通过分子对接技术进一步验证阿魏酸与关键靶点的结合能力;最后在细胞和动物水平上探究阿魏酸对KU812细胞脱颗粒、小清蛋白致敏小鼠过敏症状和血清特异抗体含量的影响,评价阿魏酸对小清蛋白引起食物过敏反应的缓解效果。结果表明:筛选出阿魏酸缓解食物过敏的重要潜在靶点有46个,关联靶点富集在Th17、JAK-STAT和炎症性肠病等通路,阿魏酸与NAKB1、STAT3、IL2、JAK2靶蛋白有较好的结合活性,结合能均低于−4.0 kJ/mol;同时阿魏酸可以降低敏化KU812细胞释放组胺和IL-6的含量,减轻小清蛋白诱导的致敏小鼠过敏症状以及显著降低血清中特异抗体含量,缓解其过敏反应。阿魏酸具有潜在缓解食物过敏的能力,研究结果为研发抗过敏类药物治疗食物过敏提供理论依据。

阿魏酸  /  致敏性  /  网络药理学  /  分子对接

Network pharmacology and Swiss Target Prediction were used to retrieve the associated targets of ferulic acid in relation to food hypersensitivity in this paper, and the key targets and action pathways of ferulic acid in alleviating food allergies were identified by conducting enrichment prediction of GO and KEGG pathways. The binding ability of ferulic acid to these key targets was further validated via molecular docking technology. Finally, the effects of ferulic acid on degranulation of KU812 cells, allergic symptoms and serum specific antibody contents of the sensitized mice by parvalbumin were investigated at the cellular and animal levels, thereby evaluating the efficacy of ferulic acid in alleviating parvalbumin sensitization. The results indicated that 46 crucial targets of ferulic acid for alleviating food allergy were identified. The relevant targets were significantly enriched in pathways including Th17, JAK-STAT, and inflammatory bowel disease. Ferulic acid exhibited favorable binding activity with target proteins NAKB1, STAT3, IL2, and JAK2, and the binding energy all lower than −4.0 kJ/mol. Meanwhile, ferulic acid significantly reduced the release ability of histamine and interleukin-6 in sensitized KU812 cells, mitigated allergic symptoms, decreased the contents of specific antibodies and allergic mediators in the serum of parvalbumin-induced sensitized mice, thereby alleviating their allergic responses. Therefore, ferulic acid has the potential to alleviate food allergies, and the research results provide a theoretical foundation for the development of anti-allergy drugs to treat food allergies.

ferulic acid  /  sensitization  /  network pharmacology  /  molecular docking
章开, 曾姝, 魏斐, 刘俊. 阿魏酸缓解小清蛋白致敏性的效果评价. 食品工业科技, 2026 , 47 (11) : 426 -432 . DOI: 10.13386/j.issn1002-0306.2025060021
Kai ZHANG, Shu ZENG, Fei WEI, Jun LIU. Evaluation of the Effect of Ferulic Acid in Alleviating the Sensitization of Parvalbumin[J]. Science and Technology of Food Industry, 2026 , 47 (11) : 426 -432 . DOI: 10.13386/j.issn1002-0306.2025060021
由食物引起的过敏反应呈现逐年增长趋势,严重影响了患者及其家庭的生活,已成为广泛关注的公共健康问题[1−2]。而鱼类是最容易引起过敏的食物之一,其主要过敏原是小清蛋白,分子量在10~14 kDa,属于EF手性蛋白家族。据报道,超过90%的鱼类过敏是由小清蛋白引起的,且小清蛋白广泛存在于各种鱼类中[3]。因此,如何消减小清蛋白引起的食物过敏对保障人类健康生活具有重要的现实意义。
临床上主要采取药物治疗、免疫疗法、靶向治疗等策略治疗食物过敏,但没有较好的治愈手段,其中过敏原特异性免疫疗法被认为是在临床上能治疗IgE介导过敏疾病最有效的途径[4];第二代抗组胺药物是治疗轻度过敏反应的首选药物,但存在耐药性和严重的副作用等[5]。目前,物理法、化学法及生物法等被用来降低致敏蛋白的过敏性,如:表儿茶素与 Ara h1的表位结合导致其空间结构发生变化,降低了其致敏性[6];白藜芦醇-卵清蛋白复合物的消化率会显著提高,使卵清蛋白潜在的致敏性显著降低[7];β-乳球蛋白与多酚化合物的共价偶联也会降低其致敏能力[8−11];多酚类化合物可从过敏原、免疫系统和肠道菌群三方面发挥对过敏反应的干预作用[12]。因此,挖掘能缓解过敏反应的多酚类化合物及其脱敏机制的研究成为目前研究的热点和难点。
网络药理学在系统研究药物、靶点、途径和疾病之间相互关系中表现出整体性和有效性[13–14],如:Peng等[15]采用网络药理学结合生化药理学研究三子汤通过调节Th1/Th2平衡减轻过敏性哮喘症状;薛静雯[16]通过体内外实验和网络药理学探讨枳实总黄酮提取物抗过敏的活性机制。阿魏酸是一种天然酚类化合物,具有抗肿瘤、抗炎等生物活性[17],可通过增强转化生长因子诱导T细胞扩增,缓解炎症。前期发现阿魏酸-葡萄糖通过调节肠道菌群、花生四烯酸和色氨酸代谢途径来降低β-乳球蛋白致敏性[18],但基于网络药理学从细胞和动物方面探究阿魏酸缓解食物过敏的机制还鲜有报道。
本文首先运用网络药理学方法筛选阿魏酸与食物过敏的共同作用靶点,构建蛋白质互作网络并识别核心靶点;通过GO功能注释和KEGG通路富集分析预测其潜在作用途径;结合分子对接技术验证阿魏酸与关键靶点的结合特性。进一步通过体外实验评估阿魏酸对IgE介导的KU812细胞组胺和IL-6释放量的影响,并建立小清蛋白致敏小鼠模型,从过敏症状评分、免疫器官指数、血清特异性抗体水平等方面评价阿魏酸的抗过敏功效,为开发基于天然产物的食物过敏干预策略提供理论依据。
小清蛋白 自制;阿魏酸(99.00%) 北京索莱宝科技有限公司;小鼠免疫球蛋白G(Immunoglobulin G,IgG)、免疫球蛋白E(Immunoglobulin E,IgE)ELISA试剂盒、白介素-6、组胺试剂盒 江苏酶免实业有限公司;山羊抗鼠IgE-HRP、山羊抗鼠IgG-HRP 美国Sigma公司;KU812细胞 武汉尚恩生物技术有限公司;3种鱼类过敏血清效价分别为0.36、2.4、0.83 kUA/L 江西省儿童医院;BALB/c雌性小鼠 购自浙江维通利华实验动物技术有限公司[SCXK(浙)2024-0001]。
Synergy H1酶标仪 美国Bio Tek公司;5430R冷冻离心机 德国艾本德公司;SR160W二氧化碳培养箱 上海舍岩仪器有限公司。
为预测阿魏酸作用靶点,综合利用多源数据库进行分析。首先通过PubChem数据库(https://pubchem.ncbi.nlm.nih.gov)获取阿魏酸的结构信息,而后利用SEA数据库(http://sea.bkslab.org/)、TCMSP数据库(https://www.tcmsp-e.com/index.php)、Swiss Target Prediction数据库(https://swisstargetprediction.ch)、PharmMapper数据库(http://lilab-ecust.cn/pharmmapper/index.html)及SuperPred数据库(https://prediction.charite.de/subpages/target_prediction.php)进行阿魏酸靶点筛选,收集上述数据库的预测靶点,通过UniProt数据库将靶点转换为对应的基因名称,整合数据、去除重复值,获取阿魏酸作用靶点。
通过MeSH网站检索疾病名称,确定食物过敏的标准化学术语。利用Genecards数据库、OMIM数据库、TTD数据库、CTD数据库以“Food Hypersensitivity”为关键词进行靶点查询。整合数据、去除重复值,同样统一其名称为人类基因标准名,最终获取食物过敏相关靶点。
利用在线绘图工具Venny 2.1.0(https://bioinfogp.cnb.csic.es/tools/venny)识别阿魏酸与食物过敏之间的交集靶点。为深入探究两者交集靶点之间的蛋白相互作用,借助String数据库(https://string-db.org)进行分析并构建PPI网络图,设定物种参数为人,置信度阈值大于0.4,确保所获取的相互作用信息具有较高的可信度,将分析完成的文件导入软件Cytoscape 3.10.0,借助Cytoscape软件对分析结果进行可视化。
为深入研究阿魏酸与食物过敏交集靶点所涉及的关键信号通路和细胞功能,将1.2.3获得的交集靶点导入DAVID数据库(http://david.ncifcrf.gov)进行GO和KEGG通路分析。分析过程中,标识符、列表类型和物种分别设置为官方基因符号、基因列表和人。统计学上,P<0.05被认为具有显著性,表明所研究的靶点在相关通路或功能中显著富集。使用微生信在线平台(http://www.bioinformatics.com.cn)对分析结果进行图表展示。
首先利用PDB蛋白质数据库(https://www.rcsb.org)获取多个靶点蛋白的三维结构,再通过PubChem数据库(https://pubchem.ncbi.nlm.nih.gov)获取阿魏酸三维结构。采用PYMOL软件对分子结构前处理(加氢、除水、去配体等),获取符合对接模式的三维结构。以阿魏酸为配体,靶点蛋白为受体,借助AutoDockTools 1.5.6软件中的AutoDock Vina进行分子对接,使用PyMOL软件对结果进行可视化。
参照前期报道[19]的方法,将KU812细胞置于37 ℃、5%CO2的培养箱中培养,培养基为RPMI-1640(含20%胎牛血清及1%青霉素/链霉素),隔天换液或传代。待细胞生长稳定后,将其浓度调整为1×106个/mL,以500 μL/孔接种到48孔培养板中,边缘孔加入等量PBS溶液。培养24 h后,每孔加入50 μL 2.0 mg/mL经0.22 μm水相膜过滤的鱼类过敏患者血清(v/v=50:1)敏化处理。敏化24 h后,实验组加入50 μL 0.5 mg/mL阿魏酸(ferulic acid,FA)进行刺激命名为FA组,对照组不加FA命名为PV组,孵育4 h。Normal组为正常细胞。最后离心(10000×g,5 min,4 ℃)收集上清液,按照试剂盒说明书检测上细胞清液中组胺和白介素-6的释放量。
参照贾斌梅[20]的方法,构建小清蛋白为过敏原诱导的BALB/c雌性小鼠食物过敏模型。动物实验方案经江西省肿瘤医院医学伦理委员会批准(伦理编号2024ky091),并按照中国动物福利指南(GB/T35892-2018)实施。具体方法为:30只BALB/c雌性小鼠(3~4周,约12 g)在20~26 ℃的动物室内自适应喂养1周。然后,随机分为对照组(Control组)、小清蛋白致敏组(PV组)、阿魏酸剂量组(FA组),每组小鼠正常饮水喂食。
致敏处理阶段:在实验的第0 d和第14 d,对各组小鼠进行腹腔注射,Control组注射200 µL/只的PBS与铝佐剂(1:1)混合液;PV组和FA组注射200 µL/只的混合液,成分比例为小清蛋白(0.25 μg/μL)、PBS及铝佐剂(2:1:1)。
灌胃处理及过敏激发:第15~26 d期间,正常喂养小鼠。从第27 d起,每日对各组小鼠实施灌胃处理,Control组和PV组灌胃2 mL PBS溶液(对照),FA组灌胃2 mL阿魏酸(90 mg/kg,PBS溶解)溶液;在第28~40 d期间,每3 d进行一次过敏激发,激发前1 h,小鼠禁食(不禁水),PV组和FA组灌胃2 mL 20 mg/mL小清蛋白,Control组灌胃等量PBS作为对照,共进行5次过敏激发。
样本采集与保存:第5次激发后1 h内采集尾静脉血清,−80 ℃冻存备用;第41 d时处死小鼠,收集眼球血清、脾脏及胸腺,−80 ℃保存待后续分析。
基于上述建立的小鼠过敏模型,参照前期报道的方法[21],对小鼠过敏性指标进行测定:每次激发后观察小鼠1 h进行过敏症状评分;在第五次灌胃激发结束后,在1 h内每隔20 min测量小鼠的体温;在无菌超净工作台内对实验小鼠实施解剖手术,分别分离并摘取脾脏及胸腺组织,随后仔细剔除器官表面附着的脂肪与结缔组织,并用生理盐水进行充分冲洗,随后准确称量脾脏及胸腺组织湿重,通过器官指数(mg/g)=器官重量(mg)/小鼠体重(g)公式计算各组小鼠的器官指数。此外,根据试剂盒说明书对小鼠血清中IgE和IgG水平进行测定。
所有实验均进行3次重复,所有结果均以平均值±标准偏差进行表示。数据的统计分析及显著性差异分析均采用SSPS 27.0软件进行,使用软件Origin 2021作图。
阿魏酸的Pubchem CID是445858,在Pubchem数据库中检索到的阿魏酸二维和三维结构,SMILES式为COC1=C(C=CC(=C1)/C=C/C(=O)O)O。使用TCMSP、Swiss Target Prediction、PharmMapper、Super Pred以及SEA五个数据库搜索阿魏酸靶点,设定筛选条件Swiss Target Prediction、PharmMapper 数据库可能性>0分。筛选后从TCMSP、Swiss Target Prediction、PharmMapper、Super Pred及SEA五个数据库分别获得16、60、246、78及278个靶点,将上述所有靶点整合、转换基因名并去除重复值后共得到548个靶点。从GeneCards(Relevance Score>10)、OMIM以及CTD(Inference Score>10)数据库中筛选、去重后分别获得122、4及2723个靶点,而TTD数据库未检索到相关靶点。将上述所有靶点整合、转换基因名并去除重复值后共得到2834个靶点。进一步与阿魏酸靶点取交集,最终筛选出46个交集靶点(图1)。这些靶点被初步确认为阿魏酸缓解食物过敏的潜在作用靶点。
使用STRING数据库对46个靶点进行了PPI分析,结果如图2所示。图中共有46个节点,其中13个节点属于游离节点,线条代表靶点蛋白之间存在的联系,共有93条。这表明46个靶点中有33个之间是紧密联系的,初步判断是阿魏酸影响食物过敏的关键靶点蛋白,同时也说明阿魏酸可能通过多种蛋白和多条通路来影响食物过敏。
如图3所示,靶点网络图中的关键节点蛋白包括ALB(degree=16)、ESR1(degree=15)、NFKB1(degree=13)、STAT3(degree=13)、EGFR(degree=13)、MPO(degree=11)、IL2(degree=11)、KIT(degree=10)、JAK2(degree=10)及CCL5(degree=10)等。这些靶点大多数与蛋白质代谢、能量代谢、细胞增殖分化以及炎症和免疫反应通路有关,可能是阿魏酸缓解食物过敏的潜在关键靶点。
通过DAVID数据库进行GO功能富集分析,结果显示在生物过程(Biological Process,BP)、细胞组分(Cellular Component,CC)和分子功能(Molecular Function,MF)三个分类中,P<0.05的条目分别有37、5和17个。为了更直观地呈现结果,选取了生物过程和分子功能中富集靶点数排名前10及细胞组分的5个条目绘制了GO富集水平的柱状图,具体结果如图4所示。其中GO-BP中富集靶点数前10的条目包括蛋白水解,细胞群体增殖的调节,细胞迁移、细胞质钙离子浓度、磷脂酰肌醇3-激酶/蛋白激酶B信号转导和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)级联反应的正调控以及凋亡过程、炎症反应中细胞因子生成、RNA聚合酶II介导的转录及基因表达的负调控;GO-CC富集的条目包括细胞质基质、细胞质、线粒体、细胞外空间及线粒体呼吸链复合体Ⅰ;GO-MF富集靶点数前10的条目分别为蛋白质、血红素、蛋白激酶、同源蛋白质、金属离子结合,蛋白质同源二聚化、电子转移和激酶、组蛋白激酶、蛋白质酪氨酸激酶活性。
KEGG通路分析鉴定出25条显著相关信号通路(P<0.05),按照P值从小到大排序,取前20条通路绘制KEGG气泡图,结果如图5所示,与食物过敏机制密切相关的通路有Th17细胞分化、JAK-STAT及炎症性肠病通路等,而NFKB1、STAT3、IL2、JAK2等关键靶点均富集于上述通路中。Th17细胞及其产生的细胞因子在过敏疾病中发挥重要的作用[22];JAK-STAT信号通路参与调控细胞免疫、增殖和凋亡等生物学过程,与多种自身免疫性疾病的发病机制相关[23];Sadar等[24]发现阿魏酸可提高结肠炎小鼠结肠中的抗氧化能力,降低丙二醛和一氧化氮的表达水平,对肠上皮损伤及细胞凋亡有保护作用。这些研究发现阿魏酸具有调控免疫-炎症网络中的关键靶点的能力。
基于KEGG通路分析,采用Autodock工具对PPI网络筛选出的关键核心靶点NFKB1、STAT3、IL2、JAK2与阿魏酸进行分子对接。再结合PyMOL平台完成三维构象可视化呈现,结果如表1及图6所示,图中的黄色虚线表示氢键。阿魏酸与NFKB1、STAT3、IL2、JAK2的结合能分别为−4.9、−5.9、−5.2、−6.7 kJ/mol,均低于−4 kJ/mol,证实阿魏酸与靶蛋白具有稳定的结合能力;阿魏酸分别与NFKB1氨基酸Gln63和Ser67、STAT3氨基酸Asn86、IL2氨基酸Asn33、Lys76和Phe78以及JAK2氨基酸Leu932发生相互作用,主要通过氢键结合,氢键个数分别为2、1、3、1。阿魏酸与JAK2的结合能最低(−6.7 kJ/mol),与IL2的氢键结合数量最多(3个)。结果表明,阿魏酸可与各个靶点蛋白的关键氨基酸结合形成氢键网络,能够形成稳定的复合物。
建立鱼过敏患者血清引起的KU812细胞致敏模型评价阿魏酸缓解过敏反应的效果。结果如图7所示,与Normal组相比,PV刺激后的KU812细胞释放组胺和IL-6的含量显著增加(P<0.05),表明PV可以诱导KU812细胞进行脱颗粒。而与PV相比,FA组的组胺和IL-6释放水平显著降低(P<0.05),这与贾斌梅[20]报道的结果类似,说明阿魏酸可以有效缓解敏化细胞的致敏性。
FA对小鼠过敏评分、体温、脾脏和胸腺指数的影响结果见图8。在第5次灌胃后,Control组的小鼠均未出现任何过敏症状,而PV组小鼠的过敏评分显著上升(P<0.05),小鼠的体温显著下降(P<0.05)。与PV组相比,FA干预的小鼠过敏评分显著降低(P<0.05),体温有显著回升趋势(P<0.05),这是由于小鼠过敏后,大量接触过敏原会导致小鼠体温骤降[25];FA干预后,缓解了体温的降低,这是由于FA影响了炎症介质的释放或下丘脑体温调节中枢,缓解过敏反应进而影响体温;脾脏和胸腺指数结果如图8C~图8D所示,与Control组和FA组相比,PV组的脾脏指数有所升高,这可能是由于过敏反应引起的脾脏肥大所致;PV组和FA组脾脏和胸腺指数有差异,但无统计学意义(P>0.05)。说明阿魏酸可以有效减轻小鼠的过敏症状和减少体温变化,缓解其过敏反应,使过敏小鼠更趋向于对照组小鼠的状况。
如图9所示,PV组小鼠的血清IgE和IgG含量显著升高(P<0.05),表明PV可以使小鼠过敏,产生了IgE和IgG抗体[25]。与PV组相比,FA组IgE和IgG的含量均显著下降(P<0.05),这表明FA可以显著降低小清蛋白诱导的过敏小鼠血清中特异抗体的含量、缓解其过敏反应,这结果与小鼠过敏症状(图8)结果一致。PV组的小鼠过敏情况最严重,FA组的小鼠次之,而Control组的小鼠没有产生过敏反应。
获得548个阿魏酸作用靶点和2834个食物过敏相关的靶点,筛选到46个阿魏酸干预食物过敏的重要潜在靶点,阿魏酸可能通过Th17细胞分化、JAK-STAT信号通路及炎症性肠病通路等途径调节炎症水平来影响食物过敏,阿魏酸与多个关键靶点有较好的结合活性,结合能均低于−4.0 kJ/mol,表明阿魏酸与关键靶点蛋白可形成稳定复合物;阿魏酸使敏化KU812细胞释放的组胺和IL-6表达水平降低,有效缓解PV对细胞的敏化作用;同时阿魏酸可以减轻小清蛋白致敏引起的小鼠过敏反应症状、减少器官指数的变化,降低血清特异性IgE和IgG分泌水平。结果表明,阿魏酸对蛋白质致敏引起的食物过敏反应具有很好的干预效果,但干预效果的评价不全面,后期还需要实验对其进行全面评价。

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2026年第47卷第11期
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doi: 10.13386/j.issn1002-0306.2025060021
  • 接收时间:2025-06-05
  • 首发时间:2026-10-22
  • 出版时间:2026-06-01
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  • 收稿日期:2025-06-05
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    1江西省肿瘤医院药学部,江西南昌 330029
    2江西师范大学生命科学学院,江西南昌 330022

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刘俊(1989−)(ORCID:0000−0002−8570−5741),男,博士,副教授,研究方向:食品营养组分相互作用,E-mail:。
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2种不同金属材料的力学参数
科
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属数
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genus
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species
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Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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