Article(id=1322926662744158924, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926492627378659, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.09.042, 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=1793339895186, onlineDateStr=2026-10-30, pubDate=1757433600000, pubDateStr=2025-09-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339895186, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339895186, creator=13701087609, updateTime=1793339895186, updator=13701087609, issue=Issue{id=1322926492627378659, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='9', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1757433600000', pubDateStr='2025-09-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339854628, creator='13701087609', updateTime=1793340762858, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322930302095590169, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926492627378659, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322930302095590170, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926492627378659, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=226, endPage=230, ext={EN=ArticleExt(id=1322926662928708301, articleId=1322926662744158924, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Research Progress of Yinyanghuo(Epimedii Folium)Regulating Immune Function, columnId=1256183365644968140, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Platform of Provincial Project, runingTitle=null, highlight=null, articleAbstract=

Yinyanghuo(Epimedii Folium)is a traditional tonic traditional Chinese medicine. It has significant biological functional activity and a wide range of pharmacological effects on many major organs and tissues of the human body. Themain chemical constituents of Yinyanghuo(Epimedii Folium)are flavonoids,lignans,alkaloids,volatile oils and other trace elements. Flavonoids are the main active ingredients and have significant immunomodulatory effects on the body. The immunomodulatory effects of flavonoids such as icariin(ICA),icaritin(ICT),dehydrated icariin(AHI),icariside I(ICA I),icariin polysaccharide(EPS)and total flavonoids of icariin(EFC)have been widely reported in recent years. A number of studies have shown that the above components have significant regulatory effects on immune organs,immune cells(includingmacrophages,T lymphocytes,B lymphocytes,NK cells,LAK cells,CD3AK cells,etc.),immune factors and tumor immune microenvironment. In recent years,with the continuous deepening of clinical observation and experimental research on the regulation of immune function by Yinyanghuo(Epimedii Folium),it has provided a scientific basis for improving the immune function of the body by traditional Chinese medicine. In this paper,the research status of Yinyanghuo(Epimedii Folium)regulating immune function was reviewed in order to provide reference for the study of the immunomodulatory effect of Yinyanghuo(Epimedii Folium)or other tonic Chinese medicines.

, authors=Pan LI, Peng YU, Aoxue YU, Yulin DAI, Guangyu CHENG, Jia LIU, Tianyang XU, authorsList=Pan LI, Peng YU, Aoxue YU, Yulin DAI, Guangyu CHENG, Jia LIU, Tianyang XU, authorCompany=null, correspAuthors=Jia LIU, Tianyang XU, 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=1322926663318778574, articleId=1322926662744158924, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=淫羊藿调节免疫功能的研究进展, columnId=1256183369033965799, journalTitle=中华中医药学刊, columnName=省级项目平台, runingTitle=null, highlight=null, articleAbstract=

淫羊藿(Epimedii Folium)是一种传统补益类中药,具有显著的生物学功能活性,对人体多个主要器官和多种组织均具有广泛的药理作用。淫羊藿的主要化学成分有黄酮类、木脂素类、生物碱类、挥发油类及其他微量元素等。黄酮类化合物是其中主要的活性成分,对机体具有显著的免疫调节作用。黄酮类化合物如淫羊藿苷(ICA)、淫羊藿素(ICT)、脱水淫羊藿素(AHI)、淫羊藿次苷I(ICA I)、淫羊藿多糖(EPS)、淫羊藿总黄酮(EFC)等成分的免疫调节作用近年来被广泛报道。多项研究表明,上述成分在免疫器官、免疫细胞(包括巨噬细胞、T淋巴细胞、B淋巴细胞、NK细胞、LAK细胞、CD3AK细胞等)及免疫因子和肿瘤免疫微环境等方面均具有显著的调节作用。近年来,随着淫羊藿调节机体免疫功能的临床观察和实验研究不断深入,为中医药改善机体免疫功能低下提供了一定的科学依据,就淫羊藿调节机体免疫功能的研究现状进行综述,以期为研究淫羊藿或其他补益类中药的免疫调节作用提供参考。

, authors=李盼, 于澎, 于澳雪, 戴雨霖, 成光宇, 刘佳, 许天阳, authorsList=李盼, 于澎, 于澳雪, 戴雨霖, 成光宇, 刘佳, 许天阳, authorCompany=null, correspAuthors=刘佳, 许天阳, authorNote=

李盼(2000-),女,贵州毕节人,博士在读,研究方向:中药炮制学。

, correspAuthorsNote=
刘佳(1982-),女,吉林长春人,副教授,硕士研究生导师,博士,研究方向:中药药理学。E-mail:。
许天阳(1979-),男,吉林长春人,副教授,硕士,研究方向:中药分析学。E-mail:。
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淫羊藿调节免疫功能的研究进展
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李盼 , 于澎 , 于澳雪 , 戴雨霖 , 成光宇 , 刘佳 , 许天阳
中华中医药学刊 | 省级项目平台 2025,43(9): 226-230
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中华中医药学刊 |省级项目平台 2025 , 43 (9) : 226 -230
淫羊藿调节免疫功能的研究进展
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李盼, 于澎, 于澳雪, 戴雨霖, 成光宇, 刘佳 , 许天阳
作者信息
  • 长春中医药大学,吉林 长春 130117
通讯作者:
刘佳(1982-),女,吉林长春人,副教授,硕士研究生导师,博士,研究方向:中药药理学。E-mail:。
许天阳(1979-),男,吉林长春人,副教授,硕士,研究方向:中药分析学。E-mail:。
作者简介:

李盼(2000-),女,贵州毕节人,博士在读,研究方向:中药炮制学。

Research Progress of Yinyanghuo(Epimedii Folium)Regulating Immune Function
Pan LI, Peng YU, Aoxue YU, Yulin DAI, Guangyu CHENG, Jia LIU , Tianyang XU
Affiliations
  • Changchun University of Chinese Medicine,Changchun 130117,Jilin,China
出版时间: 2025-09-10 doi: 10.13193/j.issn.1673-7717.2025.09.042
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淫羊藿(Epimedii Folium)是一种传统补益类中药,具有显著的生物学功能活性,对人体多个主要器官和多种组织均具有广泛的药理作用。淫羊藿的主要化学成分有黄酮类、木脂素类、生物碱类、挥发油类及其他微量元素等。黄酮类化合物是其中主要的活性成分,对机体具有显著的免疫调节作用。黄酮类化合物如淫羊藿苷(ICA)、淫羊藿素(ICT)、脱水淫羊藿素(AHI)、淫羊藿次苷I(ICA I)、淫羊藿多糖(EPS)、淫羊藿总黄酮(EFC)等成分的免疫调节作用近年来被广泛报道。多项研究表明,上述成分在免疫器官、免疫细胞(包括巨噬细胞、T淋巴细胞、B淋巴细胞、NK细胞、LAK细胞、CD3AK细胞等)及免疫因子和肿瘤免疫微环境等方面均具有显著的调节作用。近年来,随着淫羊藿调节机体免疫功能的临床观察和实验研究不断深入,为中医药改善机体免疫功能低下提供了一定的科学依据,就淫羊藿调节机体免疫功能的研究现状进行综述,以期为研究淫羊藿或其他补益类中药的免疫调节作用提供参考。

淫羊藿  /  免疫调节  /  免疫功能  /  免疫反应

Yinyanghuo(Epimedii Folium)is a traditional tonic traditional Chinese medicine. It has significant biological functional activity and a wide range of pharmacological effects on many major organs and tissues of the human body. Themain chemical constituents of Yinyanghuo(Epimedii Folium)are flavonoids,lignans,alkaloids,volatile oils and other trace elements. Flavonoids are the main active ingredients and have significant immunomodulatory effects on the body. The immunomodulatory effects of flavonoids such as icariin(ICA),icaritin(ICT),dehydrated icariin(AHI),icariside I(ICA I),icariin polysaccharide(EPS)and total flavonoids of icariin(EFC)have been widely reported in recent years. A number of studies have shown that the above components have significant regulatory effects on immune organs,immune cells(includingmacrophages,T lymphocytes,B lymphocytes,NK cells,LAK cells,CD3AK cells,etc.),immune factors and tumor immune microenvironment. In recent years,with the continuous deepening of clinical observation and experimental research on the regulation of immune function by Yinyanghuo(Epimedii Folium),it has provided a scientific basis for improving the immune function of the body by traditional Chinese medicine. In this paper,the research status of Yinyanghuo(Epimedii Folium)regulating immune function was reviewed in order to provide reference for the study of the immunomodulatory effect of Yinyanghuo(Epimedii Folium)or other tonic Chinese medicines.

Yinyanghuo(Epimedii Folium)  /  immunomodulation  /  immune function  /  immune response
李盼, 于澎, 于澳雪, 戴雨霖, 成光宇, 刘佳, 许天阳. 淫羊藿调节免疫功能的研究进展. 中华中医药学刊, 2025 , 43 (9) : 226 -230 . DOI: 10.13193/j.issn.1673-7717.2025.09.042
Pan LI, Peng YU, Aoxue YU, Yulin DAI, Guangyu CHENG, Jia LIU, Tianyang XU. Research Progress of Yinyanghuo(Epimedii Folium)Regulating Immune Function[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (9) : 226 -230 . DOI: 10.13193/j.issn.1673-7717.2025.09.042
近年来,免疫失调在诸多疾病的病理生理学中出现而受到了广泛关注。针对此问题,已经进行了多项药理学研究,旨在评估植物药化学物质的潜在免疫调节作用。机体免疫系统在维持人体内稳态中发挥着重要的作用,而异常的免疫反应会导致机体关键免疫功能监视、防御和稳态失调,进而导致多种疾病的发生和恶化,例如肿瘤、感染性疾病和免疫性血小板减少症等[1]。随着对免疫反应的研究日益深入,免疫疗法已成为预防和治疗多种疾病(包括癌症、传染病、炎性疾病和自身免疫性疾病)的有效策略。因此,对具有免疫调节作用的药物进行全面综合的研究,其成果可能为未来治疗方案的制定提供更多依据。
淫羊藿又名仙灵脾、刚前,是小檗科淫羊藿属Epimedium Linn.植物,始载于《神农本草经》,列为中品,在我国具有悠久的药用历史[2]。淫羊藿化学成分众多、药理作用广泛,具有抗炎、免疫调节、抗肿瘤及神经保护活性[3-4],对生殖系统、免疫系统、心血管系统、骨骼系统、肿瘤及神经系统疾病均具有一定的作用[5-6]。其中淫羊藿苷(ICA)、淫羊藿素(ICT)、脱水淫羊藿素(AHI)、淫羊藿多糖(EPS)、淫羊藿总黄酮(EFC)等成分是淫羊藿参与免疫调节的主要活性成分,其免疫调节作用被广泛报道。本文将总结近年来中药淫羊藿免疫调节作用的研究进展,以期为研究淫羊藿或其他补益类中药的免疫调节作用提供参考。
免疫器官主要由淋巴组织构成,通常位于中枢神经系统和外围组织之间。胸腺和脾脏被视为人体最重要的中枢免疫器官,它们在维持机体免疫力方面起着关键作用。胸腺是人体免疫系统的重要组成部分,是T淋巴细胞分化、发育和成熟的场所;脾脏则是胚胎免疫细胞和成熟淋巴细胞的定居场所,也是机体清除血液性抗原的主要场所。如果胸腺和脾脏发生萎缩,将会影响人体的免疫功能。目前,胸腺指数和脾脏指数被广泛应用于衡量人体免疫功能的水平。
谭莉等[7]研究发现EPS可作为天然的免疫调节剂,促进脾淋巴细胞增殖和巨噬细胞吞噬活性。EPS还可以显著提高胸腺脏器系数[8],暗示了EPS可以促进胸腺释放成熟细胞(T细胞),从而改善细胞增殖及白细胞介素-2(IL-2)的表达。
WANG K等[9]研究通过皮下注射皮质酮建立肾阳虚综合征(KDS)小鼠模型发现,淫羊藿给药可有效提高KDS小鼠的胸腺指数和脾脏指数,降低脾脏中凋亡淋巴细胞的比例,证实淫羊藿可以通过神经内分泌免疫(NEI)网络调节下丘脑-垂体-肾上腺(HPA)轴和激活免疫系统,从而显著改善KDS小鼠的性功能。另一项研究表明,用EFC处理的免疫抑制组小鼠脾脏和胸腺指数显著高于模型组,各项免疫指标较单纯腹腔注射环磷酰胺的免疫抑制组小鼠均有改善,证明EFC对免疫抑制小鼠的免疫系统也具有保护作用[10-11]。EPS不仅可以增强机体免疫,增加成熟骨髓源树突状细胞(chBM-DCs)和脾脏淋巴细胞增殖、提高成熟chBM-DCs的吞噬率以及促进相关免疫细胞因子分泌,还可以促进外周淋巴细胞增殖,增强血液中IFN-γ、白细胞介素-4(IL-4)和IL-2以及十二指肠中白细胞介素-17(IL-17)和分泌型免疫球蛋白A(sIgA)细胞因子的释放[12]。此外,在给予ICA和ICT后,环磷酰胺诱导的免疫抑制小鼠的脾脏指数、胸腺指数和脾淋巴细胞数均显著升高,这表明ICA和ICT能够逆转小鼠化疗后的免疫抑制状态,提高小鼠的免疫功能[13-16]。
巨噬细胞(M)是人体免疫系统中至关重要的免疫调节细胞,它是由单核细胞衍生而来的一种白细胞,在机体免疫反应和防御机制中发挥着关键作用,具有重要的生物学功能。巨噬细胞和单核细胞都属于吞噬细胞,它们在先天性和适应性免疫中都扮演着不可或缺的角色,参与机体的非特异性防御(先天性免疫)和特异性防御(细胞介导的免疫),其主要功能是固定或游离细胞的形式吞噬和消化以及激活淋巴细胞或其他免疫细胞以应对病原体。
近年来的研究表明,ICA能够刺激淋巴细胞分泌IL-2、IL-4、白细胞介素-10(IL-10)和白细胞介素-12(IL-12),提示ICA可能发挥免疫增强作用,激活静止的T细胞和巨噬细胞,诱导其活化,增加巨噬细胞的吞噬能力,同时促进淋巴细胞分化和增殖,产生细胞因子,发挥免疫增强作用[17]。另一项研究表明,给予一定剂量的ICA可刺激感染金黄色葡萄球菌的小鼠的免疫应答,提高巨噬细胞的吞噬能力,促进脾淋巴细胞增殖,促进淋巴细胞分泌IL-2和IL-10,增加淋巴细胞进入S期细胞的比率,该结果证实了ICA在金黄色葡萄球菌感染小鼠中的免疫调节活性[18]。此外,ICA还可以提高环磷酰胺免疫抑制及电离辐射免疫损伤小鼠腹腔巨噬细胞的吞噬功能,恢复其巨噬细胞的吞噬功能,并能通过影响巨噬细胞因子的分泌调节小鼠的免疫功能[15-16]。当ICA和LPS同时暴露于小鼠腹腔巨噬细胞时[19],ICA组巨噬细胞的吞噬作用明显增加,且该作用呈剂量依赖性,提示ICA可通过LPS抑制炎症相关基因表达减少TNF-α和NO的过度表达来发挥免疫调节作用。ICA还能减轻氧化低密度脂蛋白(oxLDL)诱导的巨噬细胞的损伤,并且能够降低caspase-3活性,引发内质网应激(ERS),从而抑制巨噬细胞凋亡[20]。赖新强等[21]研究发现AHI不会明显影响静息状态巨噬细胞产生一氧化氮(NO)的量,但能明显抑制LPS刺激后的巨噬细胞产生NO,表明AHI可能通过抑制巨噬细胞的活化,减少了与诱导型一氧化氮合酶(iNOS)表达有关的炎症因子的释放,从而减少了NO的产生,是一种潜在的免疫抑制剂。
T淋巴细胞(T细胞)是淋巴细胞的重要组成部分,来源于骨髓的淋巴多能干细胞,在胸腺中成熟为T细胞。T细胞在体内进行特异性的细胞免疫应答,并对体液免疫应答起到重要的调节作用,它具有广泛的生物学功能,包括直接杀伤靶细胞、刺激或抑制B细胞分泌抗体、响应特异性抗原和促有丝分裂原的免疫应答,以及生成细胞因子等。B淋巴细胞(B细胞)由骨髓中的造血干细胞在抗原刺激后分化成浆细胞,合成并分泌抗体(免疫球蛋白),是体内参与免疫应答并以体液免疫为主的一个重要的细胞类群。
淋巴细胞增殖是反映机体细胞免疫最直接的指标,淫羊藿可通过T淋巴细胞和B淋巴细胞在免疫系统发挥调节作用[22]。在自身免疫性脑脊髓炎实验中[23],ICA可抑制脾细胞、淋巴结细胞和中枢神经系统单核细胞中Th1和Th17细胞的频率,抑制体外T细胞增殖和Th1、Th17细胞分化。相关动物实验研究表明ICA可抑制T细胞中STAT3的活化,使Th17细胞减少并受到抑制[24],在体内应用ICA还可抑制PI3K/AKT信号通路的转导[25],促进成纤维细胞样滑膜细胞(FLS)的凋亡,提示ICA在类风湿性关节炎的治疗中具有潜在应用价值。ZHANG X D等[26]的研究显示,ICA可以提高免疫佐剂对荷瘤DBA/2J小鼠细胞毒性T淋巴细胞的反应,使肿瘤小鼠脾细胞中阳性细胞比例明显增加,提示ICA能增强免疫佐剂的免疫原性,增强T细胞及细胞毒性T淋巴细胞(CTL)识别肿瘤细胞的能力,并为清除肿瘤细胞提供依据。EPS还能够促进鸡脾淋巴细胞增殖[27],刺激细胞因子(IL-2、IL-4、IFN-γ、IL-10、IL-12和TNF-α)的分泌,增加NO的分泌,促进骨髓来源的树突状细胞(chBM-DCs)的成熟,并增强其刺激能力、吞噬率和促进ch BM-DCs的成熟,增强MHC I类分子的表达。其他研究表明,EPS对T细胞和B细胞具有有丝分裂原样作用,并能增加裸鼠脾脏细胞的DNA合成,表明EPS是淫羊藿补肾助阳作用的重要活性成分,是一种有效的免疫系统增强剂[28]。除此之外,EPS还能促进鸡脾脏淋巴细胞和腹腔巨噬细胞的增殖,表现出良好的免疫调节活性[29-30]。
WANG C C等[31]的研究中还观察到EPS激活的巨噬细胞刺激CD4+T细胞分化并促进INF-γ的产生增加,且EPS通过调节宿主免疫系统功能在荷瘤小鼠中表现出显著的抗肿瘤活性。另一项研究发现,ICA I具有强大的抑制肿瘤生长的作用[32],它不仅能够增加荷瘤小鼠外周血和肿瘤组织中的CD8+T细胞的数量,还能够促进肿瘤细胞的凋亡,因此,EPS和ICA I被证明是一种高效的、安全的、抑制肿瘤生长的小分子化合物。此外,添加酸性淫羊藿多糖使哺乳仔猪外周血淋巴细胞免疫功能增强和特异性抗体表达增强[33],还改善其肠道形态发育,增加小肠体液免疫反应的活性。LIX J等的研究[34]还发现ICT能够抑制T细胞的活化并延长皮肤移植小鼠的存活时间,说明ICT可以作为一种潜在的免疫抑制剂。
自然杀伤细胞(natural killer cell,NK)是先天性免疫系统中的细胞毒性淋巴细胞,NK细胞不表达机体细胞重组的抗原受体,而是表达活化受体和抑制受体的随机组合;通过这些不同受体的刺激信号和抑制信号的净平衡导致对靶细胞的反应或耐受。与T细胞不同,NK细胞可能不需要MHC分子呈现抗原来识别和杀死靶细胞,在免疫监视和早期感染控制中发挥重要作用。此外,NK细胞可通过抑制活化的B细胞来抑制骨髓干细胞,并通过释放IL-2、IFN-γ和TNF-β等细胞因子、刺激粒细胞和吞噬细胞集落的形成,从而发挥免疫调节功能。淋巴因子激活的杀伤细胞(LAK)和CD3AK细胞在抗癌领域的重要作用已经被证实,它们的无毒、无免疫抑制并能特异性杀伤肿瘤细胞等优点,使其在多种抗癌方法的研究与实践中变得越来越重要,具有很高的开发潜力和良好的应用前景,成为多细胞治疗当中不可缺少的组成部分。
ICA可明显提高化疗、辐射所致的免疫抑制小鼠的NK细胞活性,并具有一定的调节作用[35]。HEW等研究[36]报道一定浓度的ICA可以提高健康受试者和肿瘤患者的LAK细胞和NK细胞活性,且ICA与IL-2具有协同作用,IL-2与适当剂量的ICA联合使用对LAK细胞的细胞活性优于单独使用IL-2对LAK细胞的活性。李晓燕等[37]的进一步探索发现,ICA不仅可逆转转化生长因子β2(TGF-β2)对LAK和CD3AK细胞的免疫抑制作用,而且能够有效提高CD3AK细胞的增殖活性,表明ICA可以通过增强免疫效应细胞的杀伤活性等方式抵御肿瘤的侵袭。
另一项研究表明,EPS对小鼠灭活猪圆环病毒(PCV)疫苗具有显著的佐剂作用[38],促进了淋巴细胞增殖,并增加了IFN-γ和IL-6的mRNA表达,显著提高了免疫小鼠的淋巴细胞转化率和抗体滴度。胡月琴[39]探究EFC对中枢免疫系统的调节作用结果显示,EFC明显增加了免疫缺陷小鼠的体质量,且低剂量的EFC明显增加了骨髓中NK细胞的数量,说明EFC对小鼠的中枢免疫系统有明显的调节作用,且不同剂量EFC的免疫调节作用是不同的。此外,CHEN G等[40]研究发现ICA I表现出较强的免疫抗肿瘤活性,直接表现为上调荷瘤小鼠外周血中包括CD4+和CD8+T细胞或NK和NKT细胞在内的多个淋巴细胞亚群,这些结果表明,ICA I通过其微生物组重塑和宿主免疫调节特性,具有明显的免疫调节功能。
免疫反应的进行不仅依赖于免疫细胞之间的相互作用,而且还受到许多其他因素的影响,其中包括抗原、补体、细胞因子和膜表面分子。这些分子可以促进机体的免疫反应,从而提高机体的抵御力,保护机体的健康。
最近的研究发现,对环磷酰胺诱导的小鼠膀胱炎模型应用ICA后[41],环磷酰胺引起的中性粒细胞增多/淋巴细胞减少现象被有效逆转,且膀胱中的抗氧化酶水平得到了明显改善,肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的产生也得到了相应减少。Toll样受体(TLR)在先天免疫系统中起着重要的作用,是ICA作用的靶点[42],ICA可以通过Ana-1鼠巨噬细胞的刺激来诱导TLR9的显著表达[43],同时还可以显著上调TLR9的下游信号通路中IL-6和TNF-α来促进TLR9的活性。此外,还有研究通过检测HaCaT细胞中炎症细胞因子TNF-α/IFN-γ的水平探究ICA的免疫调节作用,结果表明,ICA治疗阻止了炎症细胞因子的分泌和类固醇的生成,通过体外皮肤下丘脑-垂体-肾上腺轴的免疫调节来抑制炎症[44]。SAIX等[45]通过HO-1/Nrf2途径研究了心肌梗死(MI)中ICA的免疫调节机制,发现ICA可以降低TNF-α、IL-17、INF-γ和IL-6水平,通过缓解炎症因素来最大限度地减少急性心肌梗死后小鼠的心肌细胞损伤和免疫抑制反应。ICA治疗还可以扩大复发性自然流产小鼠(RSA)的调节性T细胞(Treg)数量,显著减少Th1细胞数量,降低胎盘中雷帕霉素机械靶标(mTOR)的表达,表明ICA可能通过mTOR途径增加Treg细胞扩增并减少促炎因子表达,发挥免疫调节作用[46],HUANG S Q等[47]的另一项研究还发现ICT可能通过激活TGF-β/SMAD信号通路调控Treg/Th17失衡对RSA发挥其治疗作用,这些结果凸显了ICA和ICT可作为RSA的治疗药物的潜力。
除此之外,关于ICA对支气管哮喘过程影响的研究结果表明[48-49],ICA可通过调节Th1/Th2平衡衍生的细胞因子和多种免疫相关促炎细胞因子的分泌,从而改善动物模型中哮喘诱导的气道炎症。同样地,雾化吸入ICT可显著减少支气管哮喘小鼠气道和肺血管周围的炎症细胞浸润,并抑制哮喘小鼠的杯状细胞增生[50]。另一项研究表明[51],EPS可通过上调MHCⅡ和共刺激因子(CD40、CD80、CD86)的表达,提高BMDC细胞中炎性细胞因子(IL-6、TNF-α、IL-12)的水平,促进小鼠骨髓源性树突状细胞(BMDC)的成熟和功能,表明EPS具有良好的免疫调节作用。EPS还能抑制一些细胞因子的产生,并促进chBM-DCs的活性,进而降低IL-10和TNF-α的水平,从而影响细胞介导的免疫反应[12]。
机体各系统是一个相互协调、相互制约的有机整体,每个系统都会受到其他系统的调节和影响。当肿瘤发生的时候,免疫系统也会受到其他系统的影响。在肿瘤的发生和发展过程中,免疫系统的功能也会受到不同程度的影响。例如,肿瘤细胞会通过释放免疫抑制分子来抑制免疫系统的功能,从而逃避免疫系统的识别和攻击。此外,肿瘤细胞还会通过表达免疫抑制分子来招募免疫细胞,从而进一步抑制免疫系统的功能。
ICA可通过促进肿瘤免疫、抑制肿瘤细胞增殖、侵袭、转移等多种途径对乳腺癌、结直肠癌、食管癌等多种癌症发挥抗癌作用[52-53]。陈德森等[54]在SCID小鼠前列腺癌原位移植瘤实验中发现,ICA不仅能够阻止前列腺癌的发展,还能够促进雄激素受体(AR)的磷酸化,进一步降低PTEN的表达,最终实现抗前列腺癌的目的。ICA还能明显抑制AR蛋白的表达,抑制AR在LNCaP细胞中的肿瘤易位,并显著降低LNCaP细胞中PSA蛋白的表达[55]。此外,ICA不仅有助于提高C57BL/6小鼠Lewis肺癌患者血清中IL-2的水平[56],还有助于抑制TNF-α、IL-10以及IL-17的活性,这些结果证实了ICA具有显著的免疫调控作用,从而提升了患者的抗病毒活性。在功能上,ICA可以有效地阻止IKK复合物的产生,进而抑制NFκB信号通路的传递,进一步降低肝肿瘤细胞及其他免疫抑制细胞中程序性细胞死亡配体1(PD-L1)的表达,从而增强免疫治疗的效果[57],在晚期肝细胞癌(HCC)患者中表现出安全性、持久性和抗髓系细胞免疫抑制,这与其免疫调节活性和免疫生物标志物相关[58]。ICA还可靶向EMH,阻断MDSCs的形成和激活,以此来改变肿瘤患者的免疫系统[59],增强T细胞对肿瘤细胞的杀伤力,提示ICA可通过抑制HCC小鼠脾脏MDSCs的产生,促进CTL的抗肿瘤功能,证明ICA在改善患者的免疫系统方面的潜力,表明其可能发展成为有效治疗HCC的新型配伍药物甚至独立治疗药物。侯曼婷等[60]探讨淫羊藿醇提物对体外巨噬细胞极化调控机制及对M2样巨噬细胞促进4T1乳腺癌细胞迁移和集落形成的影响时发现淫羊藿醇提物通过体外调节巨噬细胞极化减弱4T1细胞迁移和集落形成,表明淫羊藿治疗乳腺癌可能与调节肿瘤微环境有关。栾玉玲等[61]从髓系细胞角度探讨了ICA的免疫调控作用,验证ICA可通过调控MDSCs细胞凋亡及分化抑制其免疫抑制活性,抑制大肠癌转移。
其他研究表明,淫羊藿黄酮类成分异戊烯类黄酮ICT可以抑制前列腺癌LNCaP细胞系PSA的转录,并通过绑定芳烃受体(AhR)调节蛋白酶体的泛素化降解,从而促进LNCaP细胞AR和ARvs的降解,抑制LNCaP细胞AR的转录[62]。ICA I可以明显提高肿瘤微环境中的CD8+T细胞及IFN-γ[63],同时能够与蛋白吲哚胺2,3-双加氧酶1(IDO1)相互作用,抑制“免疫逃逸”,促进STATI磷酸化,进一步诱导肿瘤细胞的凋亡,是一种安全、高效的免疫抑制剂,可以有效地提升患者的免疫系统,促进机体的健康。
越来越多的证据表明,淫羊藿的主要活性成分,如ICA、ICT、AHI、ICA I、EPS、EFC等成分在免疫调节过程中发挥着至关重要的作用。一方面,这些成分通过各种信号通路下调组织细胞和细胞因子分泌促炎细胞因子,以改善因疾病导致的组织应激和损伤;另一方面这些成分通过多种途径调节LAK、CD3AK、NK细胞和T细胞、B细胞等免疫细胞及其分泌的细胞因子,从而在肿瘤、免疫抑制和细菌感染等情况下的免疫监视、稳态和防御中发挥直接作用。并且,这些成分对各种免疫细胞亚群如Th1、Th2和M2细胞以及其分泌的细胞因子时其免疫调节作用往往因所面对的情况而异。这些结果表明,ICA、ICT、AHI、ICA I、EPS、EFC等成分可以通过调节免疫系统平衡,在不同疾病中发挥着定向调节作用。
淫羊藿野生资源丰富,是临床上常用的一种中药材,迄今为止,体内和体外研究结果表明它们具有作为免疫抑制剂或免疫佐剂的临床潜力。淫羊藿含有多种活性物质,在食品、保健品、药品、化妆品等领域有着很大的应用潜力,现已开发出淫羊藿饮料、片剂、胶囊、注射液等多种产品。随着对淫羊藿中各成分构效关系、药理活性、制剂及临床应用等方面的深入研究,定将发现淫羊藿中各成分及成分群发挥免疫调节的作用机制,这将为进一步开发利用淫羊藿在机体免疫调节方面的作用提供临床依据。
  • 吉林省科技发展计划项目(20210204035YY; 20230204034YY; YDZJ202201ZYTS205)
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2025年第43卷第9期
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doi: 10.13193/j.issn.1673-7717.2025.09.042
  • 首发时间:2026-10-30
  • 出版时间:2025-09-10
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吉林省科技发展计划项目(20210204035YY; 20230204034YY; YDZJ202201ZYTS205)
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    长春中医药大学,吉林 长春 130117

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刘佳(1982-),女,吉林长春人,副教授,硕士研究生导师,博士,研究方向:中药药理学。E-mail:。
许天阳(1979-),男,吉林长春人,副教授,硕士,研究方向:中药分析学。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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