Article(id=1322912310708286117, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322912162913596032, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.01.043, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793336473395, onlineDateStr=2026-10-30, pubDate=1736438400000, pubDateStr=2025-01-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793336473395, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793336473395, creator=13701087609, updateTime=1793336473395, updator=13701087609, issue=Issue{id=1322912162913596032, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='1', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1736438400000', pubDateStr='2025-01-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793336438157, creator='13701087609', updateTime=1793340633627, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929760048906989, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322912162913596032, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929760048906990, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322912162913596032, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=241, endPage=246, ext={EN=ArticleExt(id=1322912311094162086, articleId=1322912310708286117, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Research Progress on Antiviral Substance Basis and Mechanism of Huangqi(Astragali Radix), columnId=1256183365644968140, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Platform of Provincial Project, runingTitle=null, highlight=null, articleAbstract=

Huangqi(Astragali Radix)is a kind of traditional Chinese medicine for strengthening and invigorating Qi,and it is one of the commonly used traditional Chinese medicine in clinic. Huangqi(Astragali Radix)contains a variety of chemical components,including polysaccharides,flavonoids and saponins,which have antiviral,anti-tumor,immune regulation and other pharmacological effects,among which the antiviral effect is prominent. The effect of anti-virus of Huangqi(Astragali Radix)can be achieved in a variety ofways,such as directly killing the virus,blocking the absorption and penetration of the virus into the cell,inhibiting the replication and release of the virus,inhibiting the synthesis and expressions of viral RNA and protein,promoting the development of immune organs,promoting innate immunity,enhancing cellular and humoral immunity and regulating related signaling pathways. The antiviral effectof Huangqi(Astragali Radix)has the characteristics of safety,low toxicity and high efficiency,which isworthy of further development and research. This article summarized the pharmacodynamic material basis and mechanism of Huangqi(Astragali Radix)antiviral effect,and provided theoretical basis for its development,utilization and clinical research of traditional Chinese medicine.

, authors=Haixiao SU1, Jian HOU1, Qifeng LIU2, Lin HOU1, authorsList=Haixiao SU, Jian HOU, Qifeng LIU, Lin HOU, authorCompany=null, correspAuthors=Lin HOU, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, 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=1322912311723307690, articleId=1322912310708286117, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=黄芪抗病毒药效物质基础和作用机制研究进展, columnId=1256183369033965799, journalTitle=中华中医药学刊, columnName=省级项目平台, runingTitle=null, highlight=null, articleAbstract=

黄芪是扶正补气的中药,是临床常用的中药之一。黄芪含有多种化学成分,包括多糖类、黄酮类和皂苷类等,具有抗病毒、抗肿瘤、调节免疫功能等药理作用,其中抗病毒作用突出。黄芪抗病毒可通过多种方式实现,如直接杀灭病毒、阻滞病毒对细胞的吸附穿入、抑制病毒的复制和释放、抑制病毒RNA和蛋白质的合成与表达,还可促进免疫器官的发育、增强先天免疫、增强细胞免疫和体液免疫及调节相关信号通路等。黄芪抗病毒具有安全、低毒、高效等特点,值得进一步开发研究。总结了黄芪抗病毒的药效物质基础及作用机制,为其开发利用及其中药临床研究提供理论依据。

, authors=苏海潇1, 侯建1, 刘启峰2, 侯林1, authorsList=苏海潇, 侯建, 刘启峰, 侯林, authorCompany=null, correspAuthors=侯林, authorNote=

苏海潇(1996-),男,山东济宁人,硕士在读,研究方向:中药新药新制剂。

, correspAuthorsNote=
侯林(1984-),男,山东兰陵人,副教授,博士,研究方向:中药新药。E-mail:。
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苏海潇(1996-),男,山东济宁人,硕士在读,研究方向:中药新药新制剂。

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苏海潇(1996-),男,山东济宁人,硕士在读,研究方向:中药新药新制剂。

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M,WANG Y,et al.The anti-DHAV activities of Astragalus polysaccharide and its sulfate compared with those of BSRPS and its sulfate[J].Carbohydr Polym,2015,117:339-345., articleTitle=The anti-DHAV activities of Astragalus polysaccharide and its sulfate compared with those of BSRPS and its sulfate, refAbstract=null), Reference(id=1322912760589320927, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912310708286117, doi=null, pmid=null, pmcid=null, year=2017, volume=242, issue=3, pageStart=344, pageEnd=353, url=null, language=null, rfNumber=[74], rfOrder=73, authorNames=WANG Y, CHEN Y, DU H, journalName=Exp Biol Med(Maywood), refType=null, unstructuredReference=WANG Y,CHEN Y,DU H,et al.Comparison of the anti-duck hepatitis A virus activities of phosphorylated and sulfated Astragalus polysaccharides[J].Exp Biol Med(Maywood),2017,242(3):344-353., articleTitle=Comparison of the anti-duck hepatitis A virus activities of phosphorylated and sulfated Astragalus polysaccharides, refAbstract=null), Reference(id=1322912760656429792, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912310708286117, doi=null, pmid=null, pmcid=null, year=2016, volume=34, issue=2, pageStart=399, pageEnd=402, url=null, language=null, rfNumber=[75], rfOrder=74, authorNames=何仙芳, 费霖莉, 宁玉梅, journalName=中华中医药学刊, refType=null, unstructuredReference=何仙芳,费霖莉,宁玉梅.黄芪多糖对沙眼衣原体重组MOMP免疫增效作用的研究[J].中华中医药学刊,2016,34(2):399-402., articleTitle=黄芪多糖对沙眼衣原体重组MOMP免疫增效作用的研究, refAbstract=null), Reference(id=1322912760723538657, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912310708286117, doi=null, pmid=null, pmcid=null, year=2016, volume=2016, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[76], rfOrder=75, authorNames=ABDULLAHIA Y, KALLON S, YU X, journalName=Biomed Res Int, refType=null, unstructuredReference=ABDULLAHIA Y,KALLON S,YU X,et al.Vaccination with Astragalus and ginseng polysaccharides improves immune response of chickens against H5N1 avian influenza virus[J].Biomed Res Int,2016,2016:1510264., articleTitle=Vaccination with Astragalus and ginseng polysaccharides improves immune response of chickens against H5N1 avian influenza virus, refAbstract=null), Reference(id=1322912760786453218, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912310708286117, doi=null, pmid=null, pmcid=null, year=2020, volume=104, issue=6, pageStart=1719, pageEnd=1726, url=null, language=null, rfNumber=[77], rfOrder=76, authorNames=XUE L, WANG D, ZHANG D, journalName=JAnim Physiol Anim Nutr(Berl), refType=null, unstructuredReference=XUE L,WANG D,ZHANG D,et al.The immune adjuvant effect of Astragalus polysaccharide on in ovo injection of Newcastle disease vaccine[J].JAnim Physiol Anim Nutr(Berl),2020,104(6):1719-1726., articleTitle=The immune adjuvant effect of Astragalus polysaccharide on in ovo injection of Newcastle disease vaccine, refAbstract=null), Reference(id=1322912760849367779, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912310708286117, doi=null, pmid=null, pmcid=null, year=2019, volume=135, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[78], rfOrder=77, authorNames=SHAN C, SUN B, DALLOUL R A, journalName=Microb Pathog, refType=null, unstructuredReference=SHAN C,SUN B,DALLOUL R A,et al.Effectof the oral administration of astragalus polysaccharides on jejunum mucosal immunity in chickens vaccinated against Newcastle disease[J].Microb Pathog,2019,135:103621., articleTitle=Effectof the oral administration of astragalus polysaccharides on jejunum mucosal immunity in chickens vaccinated against Newcastle disease, refAbstract=null), Reference(id=1322912760920670948, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912310708286117, doi=null, pmid=null, pmcid=null, year=2007, volume=86, issue=12, pageStart=2530, pageEnd=2535, url=null, language=null, rfNumber=[79], rfOrder=78, authorNames=QIU Y, HU Y L, CUIB A, journalName=Poult Sci, refType=null, unstructuredReference=QIU Y,HU Y L,CUIB A,et al.Immunopotentiating effects of four Chinese herbal polysaccharides administered at vaccination in chickens[J].Poult Sci,2007,86(12):2530-2535., articleTitle=Immunopotentiating effects of four Chinese herbal polysaccharides administered at vaccination in chickens, refAbstract=null), Reference(id=1322912760979391205, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912310708286117, doi=null, pmid=null, pmcid=null, year=2019, volume=37, issue=28, pageStart=3638, pageEnd=3645, url=null, language=null, rfNumber=[80], rfOrder=79, authorNames=YAKUBOĞULLAR N, GENÇR, ÇÖVEN F, journalName=Vaccine, refType=null, unstructuredReference=YAKUBOĞULLAR N,GENÇR,ÇÖVEN F,et al.Developmentof adjuvant nanocarrier systems for seasonal influenza A(H3N2)vaccine based on AstragalosideⅦand gum tragacanth(APS)[J].Vaccine,2019,37(28):3638-3645., articleTitle=Developmentof adjuvant nanocarrier systems for seasonal influenza A(H3N2)vaccine based on AstragalosideⅦand gum tragacanth(APS), refAbstract=null), Reference(id=1322912761042305766, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912310708286117, doi=null, pmid=null, pmcid=null, year=2022, volume=53, issue=15, pageStart=4781, pageEnd=4794, url=null, language=null, rfNumber=[81], rfOrder=80, authorNames=李泽宇, 郝二伟, 曹瑞, journalName=中草药, refType=null, unstructuredReference=李泽宇,郝二伟,曹瑞,等.药食同源中药防治现代病毒性疫病的应用规律及机制分析[J].中草药,2022,53(15):4781-4794., articleTitle=药食同源中药防治现代病毒性疫病的应用规律及机制分析, refAbstract=null)], funds=[Fund(id=1322912751579955860, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912310708286117, awardId=2021CXGC010511; 2020CXGC010505, language=CN, fundingSource=山东省重点研发计划项目(重大科技创新工程)(2021CXGC010511; 2020CXGC010505), fundOrder=null, country=null), 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多糖剂量疫苗实验动物作用效果和机制文献
名称剂量/(μg)
黄芪多糖(百分含量79.50%)100、200、400 mg/kg无活性禽流感疫苗(H5N1亚型)0.3 mL黄羽类肉鸡增加IL-2、IL-10、TNF-α和IFN-β的表达、活化巨噬细胞、升高抗体滴度[76]
黄芪多糖精制1 mg新城疫(ND)疫苗0.3 mL无特定病原体的Leghorn卵提高了血清抗体滴度,增加IFN-γ、IL-2、IL-4和IL-6的浓度来增强的体液和细胞免疫,促进淋巴细胞增殖能力以及改善CD4+和CD8+T细胞的频率[77-78]
水提醇沉法(含量65.10%)0.5 mL新城疫(ND)-传染性支气管炎病毒活疫苗100 μg白罗马公鸡促进CD4+T淋巴细胞的分化或增殖来增强细胞免疫,提高ND抗体滴度,降低病毒滴度[79]
黄芪多糖500 μgHBV疫苗(pcDS2)100 μg6~8周龄雌性Balb/c小鼠诱导CD4+T细胞产生IL-4、IL-2和IFN-γ,并增强CD8+T细胞的IFN-γ表达;增加HBsAg特异性抗体水平以及T细胞的增殖活性;促进DC成熟和抑制Treg频率[65]
黄芪多糖10、25、75 μg甲型流感(H3N2)疫苗瑞士白化病小鼠通过诱导Th1/Th2平衡以及IL-17和IgG1抗体的产生[80]
), ArticleFig(id=1322912751428960915, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912310708286117, language=CN, label=表1, caption=

黄芪多糖对不同疫苗佐剂的应用

, figureFileSmall=null, figureFileBig=null, tableContent=
多糖剂量疫苗实验动物作用效果和机制文献
名称剂量/(μg)
黄芪多糖(百分含量79.50%)100、200、400 mg/kg无活性禽流感疫苗(H5N1亚型)0.3 mL黄羽类肉鸡增加IL-2、IL-10、TNF-α和IFN-β的表达、活化巨噬细胞、升高抗体滴度[76]
黄芪多糖精制1 mg新城疫(ND)疫苗0.3 mL无特定病原体的Leghorn卵提高了血清抗体滴度,增加IFN-γ、IL-2、IL-4和IL-6的浓度来增强的体液和细胞免疫,促进淋巴细胞增殖能力以及改善CD4+和CD8+T细胞的频率[77-78]
水提醇沉法(含量65.10%)0.5 mL新城疫(ND)-传染性支气管炎病毒活疫苗100 μg白罗马公鸡促进CD4+T淋巴细胞的分化或增殖来增强细胞免疫,提高ND抗体滴度,降低病毒滴度[79]
黄芪多糖500 μgHBV疫苗(pcDS2)100 μg6~8周龄雌性Balb/c小鼠诱导CD4+T细胞产生IL-4、IL-2和IFN-γ,并增强CD8+T细胞的IFN-γ表达;增加HBsAg特异性抗体水平以及T细胞的增殖活性;促进DC成熟和抑制Treg频率[65]
黄芪多糖10、25、75 μg甲型流感(H3N2)疫苗瑞士白化病小鼠通过诱导Th1/Th2平衡以及IL-17和IgG1抗体的产生[80]
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黄芪抗病毒药效物质基础和作用机制研究进展
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苏海潇 1 , 侯建 1 , 刘启峰 2 , 侯林 1
中华中医药学刊 | 省级项目平台 2025,43(1): 241-246
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中华中医药学刊 |省级项目平台 2025 , 43 (1) : 241 -246
黄芪抗病毒药效物质基础和作用机制研究进展
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苏海潇1, 侯建1, 刘启峰2, 侯林1
作者信息
  • 1.山东中医药大学青岛中医药科学院,山东 青岛 266000
  • 2.泰安市立医院,山东 泰安 271000
通讯作者:
侯林(1984-),男,山东兰陵人,副教授,博士,研究方向:中药新药。E-mail:。
作者简介:

苏海潇(1996-),男,山东济宁人,硕士在读,研究方向:中药新药新制剂。

Research Progress on Antiviral Substance Basis and Mechanism of Huangqi(Astragali Radix)
Haixiao SU1, Jian HOU1, Qifeng LIU2, Lin HOU1
Affiliations
  • 1.Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Qingdao 266000, Shandong, China
  • 2.Taian Hospital, Taian 271000, Shandong, China
出版时间: 2025-01-10 doi: 10.13193/j.issn.1673-7717.2025.01.043
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黄芪是扶正补气的中药,是临床常用的中药之一。黄芪含有多种化学成分,包括多糖类、黄酮类和皂苷类等,具有抗病毒、抗肿瘤、调节免疫功能等药理作用,其中抗病毒作用突出。黄芪抗病毒可通过多种方式实现,如直接杀灭病毒、阻滞病毒对细胞的吸附穿入、抑制病毒的复制和释放、抑制病毒RNA和蛋白质的合成与表达,还可促进免疫器官的发育、增强先天免疫、增强细胞免疫和体液免疫及调节相关信号通路等。黄芪抗病毒具有安全、低毒、高效等特点,值得进一步开发研究。总结了黄芪抗病毒的药效物质基础及作用机制,为其开发利用及其中药临床研究提供理论依据。

黄芪  /  抗病毒  /  免疫调节  /  物质基础  /  作用机制

Huangqi(Astragali Radix)is a kind of traditional Chinese medicine for strengthening and invigorating Qi,and it is one of the commonly used traditional Chinese medicine in clinic. Huangqi(Astragali Radix)contains a variety of chemical components,including polysaccharides,flavonoids and saponins,which have antiviral,anti-tumor,immune regulation and other pharmacological effects,among which the antiviral effect is prominent. The effect of anti-virus of Huangqi(Astragali Radix)can be achieved in a variety ofways,such as directly killing the virus,blocking the absorption and penetration of the virus into the cell,inhibiting the replication and release of the virus,inhibiting the synthesis and expressions of viral RNA and protein,promoting the development of immune organs,promoting innate immunity,enhancing cellular and humoral immunity and regulating related signaling pathways. The antiviral effectof Huangqi(Astragali Radix)has the characteristics of safety,low toxicity and high efficiency,which isworthy of further development and research. This article summarized the pharmacodynamic material basis and mechanism of Huangqi(Astragali Radix)antiviral effect,and provided theoretical basis for its development,utilization and clinical research of traditional Chinese medicine.

Huangqi(Astragali Radix)  /  antiviral  /  immune regulation  /  material basis  /  mechanism of action
苏海潇, 侯建, 刘启峰, 侯林. 黄芪抗病毒药效物质基础和作用机制研究进展. 中华中医药学刊, 2025 , 43 (1) : 241 -246 . DOI: 10.13193/j.issn.1673-7717.2025.01.043
Haixiao SU, Jian HOU, Qifeng LIU, Lin HOU. Research Progress on Antiviral Substance Basis and Mechanism of Huangqi(Astragali Radix)[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (1) : 241 -246 . DOI: 10.13193/j.issn.1673-7717.2025.01.043
由病毒引起的感染性疾病一直以来威胁着人类的健康和生命,据世界卫生组织(WHO)统计数据显示,全球每年约有1500万人死于病毒性感染,约占全球每年总病死率的25.5%[1]。病毒感染的预防和治疗一直以来是医学界的挑战,因此探究病毒感染的发病机制和寻找一种安全、有效的抗病毒药物尤为重要。研究发现,中医药在改善病毒感染患者临床症状、提高生活质量、改善预后等方面疗效显著,逐渐成为病毒防治的重要手段[2]。目前针对病毒性疾病,主要采用抗病毒药物如奥司他韦、利巴韦林等的治疗和疫苗防治,但抗病毒类化学合成药物长期服用后,病毒易形成逃避机制,现已成为临床上治疗病毒性疾病的棘手问题[3]。目前针对黄芪发现安全有效的抗病毒药物相对较少,明确黄芪抗病毒活性成分,发现新的有效成分以及探究其作用机制仍是黄芪抗病毒研究的主要任务之一。
中药黄芪为豆科植物蒙古黄芪Astragalus membranaceus(Fisch.)Bge. var. mongholicus(Bge.)Hsiao或膜荚黄芪Astragalus membranaceus(Fisch.)Bge.的干燥根[4],作为传统中药之一,黄芪味甘,性微温,具有补中益气、利水消肿、固汗止表、生津养血、行滞通痹等功效。黄芪首载于《神农本草经》,被位列上品,被称为“补气之最”,因具有丰富的化学成分以及强大的药理作用而备受国内外专家学者所关注[5]。近年来黄芪提纯工艺取得了很大进步,已经从黄芪中分离和鉴定出200多种化合物,主要分为多糖类、黄酮类、皂苷类、氨基酸类,还包括少量的生物碱类、木脂素类、甾醇类化合物及多种微量元素[6-7]。现代研究表明,黄芪具有抗病毒[8]、抗炎[9]、抗肿瘤[10]、抗氧化[11]和提高机体免疫力[12]等功能。在抗病毒方面对黄芪的活性成分研究主要集中在多糖和皂苷上,黄芪不仅对人患病毒,如疱疹病毒(HSV)、乙型肝炎病毒(HBV)等具有较好地抑制作用,而且对禽畜感染病毒如禽流感病毒、猪圆环病毒(PCV)等也具有良好的抑制作用[13]。本文旨在总结黄芪抗病毒活性成分及作用机制,为中药临床研究提供支持,进而为其开发利用提供依据。
黄芪多糖(APS)是从黄芪中提取的天然有效活性成分,是黄芪药理作用中起决定性作用的一类大分子物质,具有抗病毒、免疫调节、抗氧化、抗炎、抗肿瘤等生物活性[14]。黄芪多糖的提取溶剂多采用水溶液和醇溶液,纯化多采用凝胶柱色谱和DEAE纤维吸附柱进行纯化,此外,微生物发酵和酶辅助提取已成为近年来的研究热点[15]。SOLTANIM等[16]将黄芪经热水提取后用不同浓度的乙醇沉淀得到4种多糖(APS1~APS4),单糖分析表明APS1仅由葡萄糖组成,APS2均由阿拉伯糖组成,APS3由鼠李糖、葡萄糖、半乳糖和阿拉伯糖组成,APS4由半乳糖和阿拉伯糖组成。这些单糖通过不同位点所连接的多糖组分是发挥抗病毒的物质基础之一[17]。
黄芪皂苷(AS)也是黄芪所含的重要药效成分之一,目前发现的黄芪中的皂苷,常以游离态存在,具有相对的药理作用和较强的生物活性。但是皂苷很难分离,对于黄芪皂苷的研究比较缓慢。皂苷类化合物具有抗病毒、抗肿瘤、免疫调节等生物活性[18]。皂苷类提取方法和多糖类和黄酮类类似,目前,黄芪皂苷类成分主要有黄芪皂苷Ⅰ~Ⅷ,异黄芪皂苷Ⅰ、Ⅱ和Ⅳ,环黄芪苷E、F和G和黄芪甲苷Ⅰ~Ⅳ等[19]。其中黄芪甲苷(AstragalosideⅣ)是黄芪质量控制成分标志物,是黄芪发挥抗病毒等药理活性的主要物质之一,在2020版《中华人民共和国药典》中规定黄芪的干燥品中,黄芪甲苷含量不得低于0.080%[4]。
黄酮类化合物作为次级代谢产物广泛分布于各种植物中,是黄芪中最丰富的一类化学成分。研究发现,可从黄芪的根、茎、叶和花中提取分离出80余种黄酮类成分,种类繁多,主要为黄酮、异黄酮、异黄烷和紫檀素型黄酮,异黄酮种类最多,其中芒柄花素、毛蕊异黄酮和毛蕊异黄酮-7-O-甲基-D-吡喃葡萄糖苷是黄芪的重要活性成分[20-21]。其中黄芪黄酮类物质主要具有增强免疫、抗肿瘤和抑制动脉粥样硬化等作用[22],对病毒性心肌炎亦有较好的心脏保护作用。
黄芪生物碱具有多种功效,包括免疫调节、抗氧化、抗炎等生物活性[23],斜茎黄芪含有多种生物碱,且以别隐品碱、原阿片碱、坎那定碱和Oxyhydrostinine为主[24]。马晓丰等从蒙古黄芪中分离出6种生物碱成分[25]。
黄芪中含有多种有机酸类和氨基酸成分,阿魏酸、异阿魏酸、天门冬氨酸、丝氨酸、脯氨酸和精氨酸[26-27];此外,黄芪还含有Ca、Mg、Fe、Cu、Mn、Cr和Zn等多种微量元素[28]。
黄芪对病毒可起到直接杀灭作用,常用的体外细胞实验方法用于评估药物对病毒的直接灭杀作用主要包括,细胞毒性检测(MTT比色法、细胞凋亡检测、细胞毒性试剂盒等)、细胞复制抑制测定(病毒滴度测定、实时荧光定量PCR等)、细胞保护实验(细胞存活率评估和细胞凋亡程度测定等)。商蕾等[29]通过MTT比色法发现黄芪甲苷对腺病毒(HAdV3)有直接灭活作用,且病毒抑制率与药物浓度呈正相关。王志洁等[30]发现黄芪总多糖、黄芪总皂苷、黄芪总黄酮直接作用于人HSV药效显著优于阳性对照组阿昔洛韦(ACV),其中黄芪总皂苷抗单纯疱疹病毒1型(HSV-1)效果最好。刘巍等[31]探讨了黄芪溶液、葡萄糖酸锌以及二者复方对流感病毒H3N3的抑制作用,发现黄芪以直接给药形式,直接灭杀流感病毒抑制率为58.93%。刘樱等[32]发现黄芪及其提取物具有抑制、阻断和直接灭杀猪繁殖和呼吸综合征病毒(PRRSV)的能力,直接灭杀PRRSV的能力显著且稳定,黄芪单药在安全浓度6.25 mg/mL下细胞保护率能达100%以上。综上,黄芪多糖对多种病毒具有直接杀灭作用,效果显著且具有一定临床意义。
阻止病毒对细胞的吸附和穿入是一种重要抗病毒策略,通过干扰病毒与宿主细胞之间的相互作用来阻止病毒感染。病毒在体内需要经历多个环节,吸附、脱壳、复制、成熟、释放等[33]。黄芪则可以在病毒的吸附、穿入复制和释放等环节发挥抗病毒作用。卫文强等[34]通过研究发现黄芪体外抗猪传染性胃肠炎病毒(TGEV)吸附作用在黄芪浓度不低于12.50 mg/mL时显著高于对照组。商蕾等[29]发现黄芪甲苷通过破坏Had V3S的纤突阻止病毒吸附,抑制病毒对细胞的穿入。血凝素是与流感病毒的受体结合和膜融合的糖蛋白,它可以使病毒与被感染细胞相互吸附结合,在病毒入侵宿主细胞时发挥重要作用。因此,对病毒血凝素的抑制是发挥阻断病毒吸附穿入的重要方式[35]。舒莉萍探究[36]不同浓度的黄芪水提液对流感病毒血凝效价的影响,体外直接抑毒实验以及预防和治疗实验都显示黄芪A6组分(主要成分为黄芪黄酮类)能明显降低流感病毒的血凝效价。杭小英等[37]发现黄芪多糖抗大口黑鲈弹状病毒(MSRV)的作用机制可能与上调血凝素基因的表达和干扰病毒血凝素和细胞受体之间的结合有关。以上结果表明,黄芪及其提取物对病毒的吸附和穿入有一定抑制效果,且与浓度有关。
人呼吸道合胞病毒(RSV)是一种常见的呼吸道病毒,主要感染婴儿、幼儿和老年人,尤其是免疫系统较弱的人群,是导致婴幼儿急性和严重下呼吸道感染最常见的RNA病毒之一[38]。吴振波等[39]通过小鼠体内实验发现黄芪多糖可抑制RSV诱导小鼠体质量减轻,并可降低肺指数,改善肺水肿,当给药剂量为100~300 mg/(kg·d)时可通过抑制RSV复制来降低病毒滴度,且呈剂量依赖性。苏琦华等[40]发现经黄芪水提液作用的柯萨奇B病毒(CVB)在细胞模型内的病毒抗原表达减少,使Vero细胞病变程度减轻,可体外抑制持续感染细胞模型中CVB3、CVB5的增殖。ZHANG X Y等[18]研究发现总黄芪甲苷(ASTs)通过抑制EV71的复制和释放以保护ges 1细胞免受EV71病毒诱导的细胞凋亡。黄芪甲苷还可以通过抑制流感病毒(H1N1)的早期复制而发挥抗病毒活性[41-42]。另有研究者采用荧光定量PCR等技术发现黄芪多糖通过减少氧化应激和阻断NF-κB途径来抑制猪圆环病毒2型(PCV2)复制,且和浓度呈相关性[43]。综上所述,尽管黄芪及其提取物在研究中显示出对多种病毒复制和释放具有明显的抑制作用,但具体的抗病毒机制和效果可能因病毒的种类、研究条件和使用黄芪提取物的类型和浓度而有所差异。
黄芪除了通过抑制病毒的吸附和释放来发挥抗病毒作用外,还可通过抑制病毒RNA和蛋白质的合成和表达来起作用。具体来说,黄芪中的活性成分可干扰病毒复制过程中的RNA聚合酶和蛋白质翻译过程,从而抑制病毒RNA和蛋白质的合成和表达。XUE H X等[44]将采用0、100、200或400 mg/kg黄芪多糖处理PCV2感染小鼠,发现黄芪多糖(200和400 mg/kg)显著抑制PCV2病毒mRNA的表达和蛋白质的合成。为了进一步证实黄芪抗病毒的作用机制,ZHANG P等[8]采用实时qRT-PCR检测模拟细胞和病毒感染的CEK细胞中IBV基因组和亚基因组RNA水平,并以不同浓度的黄芪多糖处理,发现黄芪多糖处理的感染CEK细胞呈现出病毒RNA水平的整体降低,证实了黄芪抗病毒的作用;WU Y等[45]通过研究黄芪多糖对HP-PRRSV HN株感染猪肺微血管内皮细胞作用,发现黄芪多糖可以抑制PRRSV NmRNA的表达。GUOQ等[46]研究表明,30 μg/mL黄芪多糖显著降低了EB病毒早期蛋白Zta、Rta和eea-D的表达,显著抑制了病毒的裂解;除抑制病毒RNA和蛋白合成与表达之外,黄芪被报道可通过免疫调节方式间接发挥抗病毒作用。
黄芪还被发现可以促进免疫器官的发育,如脾脏和胸腺。它可以增加免疫细胞在这些器官中的生成和分化,并提高器官的功能。这有助于加强整体免疫系统的效能,并提高机体对病毒的免疫应答[47]。胸腺是免疫细胞(主要是T细胞)发育成熟的场所,脾具有非特异性和特异性免疫功能,含有大量的自然杀伤细胞(NK细胞)和淋巴细胞[48]。胸腺指数、脾指数、NK细胞活性、淋巴细胞增殖能力均可较好地反映免疫器官的发育程度和免疫细胞的生理功能[49]。研究表明,黄芪多糖能促进免疫器官成熟,可显著增强脾脏T细胞的增殖能力,且对于小鼠的免疫功能有明显促进作用,小鼠在感染HSV-1后,黄芪多糖组小鼠的脾脏大小明显大于模型组[50-51],这表明黄芪多糖能够增强小鼠的免疫反应,并可能对病毒感染起到保护作用。这些研究结果表明,黄芪具有调节免疫系统功能的能力,促进免疫器官发育成熟,增强T细胞增殖能力,并对免疫功能产生积极影响。
先天免疫是抵御病原体入侵的第一道防线,I型干扰素(IFN-α/β)是先天免疫反应最有效的抗病毒细胞因子之一,可诱导分泌白细胞介素,阻碍病毒蛋白合成,促进抗病毒蛋白的产生,进而发挥显著的抗病毒作用[52]。干扰素诱导的四肽重复蛋白(IFITs)对抑制病毒增殖和调节先天免疫也至关重要[53]。黄芪多糖可以上调IFI3和IFI5的表达来抑制HP-PRRSV的增殖[54]。在HSV-1感染的小鼠模型中,黄芪多糖治疗后,据报道可能导致白细胞介素-12(IL-12)和干扰素-γ(IFN-γ)水平升高,从而增强机体对病毒的抵抗力[50,55]。IL-15可诱导B细胞增殖和分化,促进T细胞和NK细胞增殖,还能协同IL-12刺激NK细胞产生IFN-γ[56]。最近的研究报道了黄芪多糖显著提高了IL-15、TNF-α、IFN-γ产生,从而可有效地抑制番鸭免受番鸭呼肠弧病毒(MDRV)感染[57]。研究表明,黄芪可以通过激活体内的吞噬细胞(MΦ)、NK细胞和补体系统,诱导多种细胞因子,如IFN-γ、TNF-α,提高对病原体的抵抗能力,从而起到增强机体的先天免疫的作用。
体液免疫作为特异性免疫应答的重要因素之一,其主要通过B细胞对抗原的识别、活化并分化为浆细胞而产生抗体来抵抗感染性疾病,抗体作为体液免疫反应的免疫分子,可以阻止病原体的入侵,中和毒素,促进病原体的吞噬和破坏,其滴度可间接反映体液免疫的状态[58]。提高B淋巴细胞的数量与活性,可促进B淋巴细胞介导的体液免疫抗体的产生,以中和并消除细胞外微生物和微生物毒素[59]。ZHANG N W等[60]研究表明,口服黄芪多糖能显著增强口蹄疫病毒小鼠的体液免疫,其机制包括增强腹腔巨噬细胞的吞噬能力,促进脾淋巴细胞的增殖和IL-4和IL-10等细胞因子的产生和抗体变化。
细胞免疫是由T淋巴细胞发挥关键作用,包括细胞毒性T细胞(CD8+ T细胞)和辅助T细胞(CD4+ T细胞),已被认为是对接种疫苗的动物进行保护并有助于病毒清除的重要因素[61],因此,T淋巴细胞增殖可作为评价细胞免疫状态的重要指标。黄芪多糖对免疫反应的调节作用,包括细胞免疫,如将Th2转移到Th1来改善免疫功能及调节因子的释放,这种转变可以增强细胞免疫功能,提高机体对细胞病原体的抵抗能力[62]。SHI L等[50]研究发现黄芪多糖和HSV-1在小鼠体内的共刺激可在8 d内显著增加局部CD8+细胞的产生,平衡T细胞亚群,改善病理变化并增强免疫力。侯明英等[63]研究表明黄芪注射液对病毒性心肌炎治疗效果的影响,结果表明,病毒性心肌炎常规治疗合用黄芪注射液组痊愈率为33.3%,有效率为91.7%,均优于仅常规治疗对照组。董湘玉等[64]发现黄芪通过提高CD8+ T细胞和CD4+ T细胞作用,抑制病毒的复制,增强T细胞、NK细胞和吞噬细胞的活性来平衡细胞因子,起到减轻病毒性心肌炎的作用,黄芪注射液能提高病毒性心肌炎的治疗效果,值得临床推广。DU X等[65]研究发现,黄芪多糖可以增加乙肝表面抗原(HBsAg)的抗体水平以及T细胞的增殖活性,诱导CD4+ T细胞产生IL-4、IL-2及IFN-γ,提高CD8+ T细胞IFN-γ的表达,诱导T细胞的活性,从而增强细胞免疫。
黄芪发挥抗病毒作用的主要信号通路是Toll样受体信号通路。Toll样受体识别病原相关分子模式,是机体抵抗感染性疾病的第一道防线[66]。TLR3、TLR4和TLR7是Toll样受体家族的3个重要成员,TLR3的激活可诱导干扰素INFs的产生,这些干扰素对抗病毒起重要作用,其激活还能促使细胞产生促炎因子和趋化因子,这些因子有助于加强机体抗病毒的宿主反应[67]。黄芪注射液(AMI)可能影响细胞增殖周期、SOD和MAD含量以及TLR3介导的信号通路中相关因子的表达而发挥抗病毒作用,能有效抑制甲型流感(H1N1)诱导的TLR3蛋白水平的上调,依赖TRIF途径可以与各种下游靶点(TBK1、TAK1、IKKα等)结合,通过这种方式,IRF3和NF-kB信号通路被激活以起到抗流感病毒的作用[68]。卢春化等[69]研究发现,黄芪多糖可通过介导TLR4/7-MyD88-NF-κB信号通路下调炎性因子TNF-α、IFN-α、IL-6、IL-β的表达,减轻炎症反应,进而缓解流感病毒所致的急性肺损伤。黄芪抗病毒作用机制见插页Ⅺ图1。
由于黄芪多糖分子量大、溶解度低等特点限制了临床应用,近年来发现适度的结构改变或加工可以极大提高黄芪多糖的生物利用度。黄芪多糖脂质体(APSL)不仅可以增强巨噬细胞的吞噬能力,提高IL-6和IL-12的含量,还能促进树突状前体细胞的增殖,增强树突状刺激T细胞增殖和呈递抗原的能力,上调IFN-γ和DC的IL-2产生,并调节了DC中CD80和CD86的表达,提高抗体滴度,提高黄芪多糖的佐剂性和药物作用。黄芪多糖脂质体可以调节免疫应答机制,有望开发成黄芪多糖的新型制剂[70-71]。通过化学修饰的手段在多糖结构中引入硫酸基团和羟基形成硫酸酯,可加强或使原多糖具有抗病毒、调节免疫、抗肿瘤、抗氧化等生物活性[72]。CHEN Y等[73]研究表明,黄芪多糖具有抗DHAV活性,硫酸化修饰可以更有效地增强黄芪多糖的抗DHAV活性。然而,WANG Y等[74]通过三偏磷酸钠、三聚磷酸钠(STMP-STPP)法和氯磺酸-吡啶方法来分别修饰黄芪多糖得到黄芪多糖磷酸(pAPS)和硫酸(sAPS)形式,发现pAPS比APS和sAPS更有效地抑制DHAV增殖,在临床试验中,pAPS显著提高了33.5%的存活率,而在体外和体内试验中,pAPS的抗DHAV活性均高于APS和sAPS。单一的疫苗往往达不到预想的效果,采用低毒高效的佐剂才能提高其免疫效果,近年来发现黄芪多糖可以增强免疫反应,提高免疫效果,黄芪作为抗病毒免疫佐剂的作用机制可能涉及多个方面,它可以增强抗原呈递细胞的活性,促进免疫细胞的增殖和功能,提高免疫细胞对病毒的识别和清除能力,是一种理想的免疫增强剂,也是当今开发疫苗佐剂的热点之一[75]。黄芪多糖作为佐剂的应用见表1。
中药因其丰富的化学成分和复杂的作用机制从而体现出多途径、多靶点的特点,已成为挖掘抗病毒药物的重要来源。黄芪药用历史悠久,有“补药之长”之称,为历代中医常用的中药之一。在防治COVID-19的实践中,根据相关纳入标准[81],共收集处方264首,涉及中药255种其中高频药食同源中药以黄芪、甘草、金银花、茯苓等为主,说明这些药食同源中药在防治现代病毒性疾病方面有着巨大潜力。黄芪和其他中药配伍应用也是中医药治疗病毒性疾病的优势所在,相关防治病毒性疾病药食同源中药药对包括黄芪-金银花、黄芪-桔梗、黄芪-藿香等,观察中药间的联合应用是否可以增强抗病毒效果以及相应地扩大应用范围仍需要进一步实验探索和研究。
黄芪中发挥抗病毒能力的化学成分有黄芪多糖、黄芪皂苷、黄芪黄酮等。黄芪多糖具有十分显著的抗病毒效果,而且应用也十分广泛,对多种人感染和动物感染的病毒都有一定的抗病毒效果,是有效的抗病毒药物,然而黄芪多糖抗病毒作用研究大多为体内试验,体外试验较少。黄芪甲苷也在抗病毒方面具有突出的效果,能够对RNA病毒和DNA病毒产生抑制作用。黄芪黄酮类抗病毒的研究并不多,目前只有研究其对CVB、人HSV的报道,但这从另一方面反映出黄芪黄酮作为抗病毒药物具有一定的潜力。黄芪及其提取物抗病毒对免疫系统具有广泛的影响,它不仅能促进脾脏、胸腺等免疫器官的发育,而且能诱导多种细胞因子如IFN-γ、TNF-α等,增强机体的先天免疫。此外,黄芪还显示出对T细胞B细胞的影响,从而增强机体的体液免疫和细胞免疫,通过激活抗病毒免疫信号通路来发挥抗病毒作用。但是不能简单地将免疫系统对病毒的作用进行简单的概括,也暗示着黄芪及其提取物抗病毒机制的复杂性。虽然黄芪各化学成分抗病毒的研究取得了不小的进展,但许多抗病毒机制尚不明确,还有很大的研究前景。
随着科学技术不断发展与完善,对于提高中药单体生物利用度以及通过化学修饰提高单体特异靶向抗病毒作用的研究还很缺乏。经文献检索后发现相关研究中使用的黄芪及其药效物质并没有明确的有效剂量,确定其中有效成分的剂量和作用机制并不容易,因此需要在后续的研究中进一步确定黄芪及其提取物的安全性和有效剂量,制定更安全的用药方案。为了充分挖掘黄芪抗病毒的作用机制,仍需更进一步的实验探索和研究加以佐证。
  • 山东省重点研发计划项目(重大科技创新工程)(2021CXGC010511; 2020CXGC010505)
  • 山东省重点研发计划项目(乡村振兴科技创新提纲行动计划)(2022TZXD0033)
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2025年第43卷第1期
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doi: 10.13193/j.issn.1673-7717.2025.01.043
  • 首发时间:2026-10-30
  • 出版时间:2025-01-10
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山东省重点研发计划项目(重大科技创新工程)(2021CXGC010511; 2020CXGC010505)
山东省重点研发计划项目(乡村振兴科技创新提纲行动计划)(2022TZXD0033)
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    1.山东中医药大学青岛中医药科学院,山东 青岛 266000
    2.泰安市立医院,山东 泰安 271000

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侯林(1984-),男,山东兰陵人,副教授,博士,研究方向:中药新药。E-mail:。
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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
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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