人参免疫调节作用研究进展
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摘要
人参是我国传统中药,具有多种生物活性,现已有大量文献报道人参在癌症、心血管疾病、神经系统疾病的治疗和机体免疫调节系统中发挥着重要作用。人参作为免疫调节剂被应用于调节机体免疫系统,其免疫调节作用及其作用机制已成为研究热点。本文综述了有关人参对固有性免疫应答和适应性免疫应答调节作用方面的研究进展,详述了人参对巨噬细胞、自然杀伤细胞和树突状细胞等几种免疫细胞的调节作用,为进一步对人参及其产品的开发提供一定的科学理论依据。
As a traditional Chinese medicine, ginseng possesses multiple different biological activities. Accumulating evidence indicates that ginseng plays an important role in the treatment of multiple diseases including cancer, cardiovascular diseases and nervous system diseases as well as the regulation of immune system.Ginseng is used in maintaining the immune system as an immunomodulator. It becomes a hot spot for its immune effect and mechanism. This paper reviews the research progress of ginseng on the regulation of innate and adaptive immune responses.And describes the regulatory effects of ginseng on macrophages, natural killer cells, dendritic cells and other immune cells in detail.Which provides a scientific theoretical foundation for the further development of ginseng and its products.
As a traditional Chinese medicine, ginseng possesses multiple different biological activities. Accumulating evidence indicates that ginseng plays an important role in the treatment of multiple diseases including cancer, cardiovascular diseases and nervous system diseases as well as the regulation of immune system.Ginseng is used in maintaining the immune system as an immunomodulator. It becomes a hot spot for its immune effect and mechanism. This paper reviews the research progress of ginseng on the regulation of innate and adaptive immune responses.And describes the regulatory effects of ginseng on macrophages, natural killer cells, dendritic cells and other immune cells in detail.Which provides a scientific theoretical foundation for the further development of ginseng and its products.
引文
[1]国家药典委员会.中华人民共和国药典:一部[K].北京:中国医药科技出版社,2015.
[2]陈霁,屈志炜,许琳,等.人参皂甙Re对多种记忆障碍的改善作用及对海马齿状回LTP的影响[C]//.中国药理学会补益药药理专业委员会.中国药理学会补益药药理专业委员会成立大会暨人参及补益药学术研讨会会议论文集.北京:中国药理学会,2011:2.
[3]许慧.人参皂苷Rgl及其代谢产物Rhl,Ppt生精保护作用的分子机制研究[D].开封:河南大学,2013.
[4]姚根兰,张娅萍,欧阳柳凤,等.人参抗疲劳作用的研究进展[J].世界中西医结合杂志,2015,10(8):1174-1177.
[5]潘鑫鑫,郑卫红.人参总皂甙抗衰老作用的实验研究[J].中国老年学杂志,1995,15(5):288-290.
[6]Song J H,hoi H J,Song H H,et al.Antiviral activity of ginsenosides against coxsackievirus B3,enterovirus 71,and human rhinovirus 3[J].Journal of Ginseng Research,2014,38(3):173-179.
[7]张南,李娜,李佳琳,等.人参、刺五加提取物对链脲佐菌素诱导糖尿病小鼠的降糖作用研究[J].天然产物研究与开发,2014,26(10):1690-1695.
[8]Wang Y,Liu Y,Zhang X Y,et al.Ginsenoside Rg1 regulates innate immune responses in macrophages through differentially modulating the NF-B and PI3K/Akt/mTOR pathways[J].International Immunopharmacology,2014,23(1):77-84.
[9]Singh V K,George C X,Singh N,et al.Combined treatment of mice with Panax ginseng extract and interferon inducer[J].Planta Medica,1983,47(4):234-236.
[10]Singh V K,Agarwal S S,Gupta B M.Immunomodulatory activity of Panax ginseng extract[J].Planta Medica,1984,50(6):462-465.
[11]Ackerknecht E H,Haushofer L.A short history of medicine[M].Maryland:JHU Press,2016.
[12]吴皓,林洪生,裴迎霞,等.人参皂甙Rg3对荷瘤及环磷酰胺化疗小鼠黏膜免疫力影响[J].中国肿瘤,2006,(6):369-371.
[13]刘艳艳,张凯,关家伟,等.人参皂苷对BALB/c小鼠肠道菌群的影响[J].现代生物医学进展,2015,(6):1041-1045.
[14]刘伟宏,龚守良.人参三醇组甙对雄性大鼠免疫器官的辐射防护作用[J].白求恩医科大学学报,1994,20(1):32-34.
[15]王庭富,孟正木.人参皂甙Rg3对免疫功能的影响[J].中国药科大学学报,1999,(2):55-57.
[16]Gordon S.The macrophage[J].Bioessays,1995,17(11):977-986.
[17]Medzhitov R,Janeway C A.Innate immunity:impact on the adaptive immune response[J].Current Opinion in Immunology,1997,9(1):4-9.
[18]Guzik T,Korbut R,Adamek-Guzik T.Nitric oxide and superoxide in inflammation[J].Physiol Pharmacol,2003,54(4):469-487.
[19]张才军,郭民,柳波,等.人参皂苷Rh1对免疫功能降低小鼠的免疫调节作用研究[J].昆明医学院学报,2009,30(11):51-54,58.
[20]管蓓蓓,曹丽,朱昌来,等.人参皂苷对巨噬细胞超微结构及MHC-II表达的影响[J].中国交通医学杂志,2008,22(3):218-220.
[21]Baek K S,Yi Y S,Son Y J,et al.In vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components[J].Journal of Ginseng Research,2016,40(4):437-444.
[22]Kang S,Park S J,Lee A Y,et al.Ginsenoside Rg3 promotes inflammation resolution through M2 macrophage polarization[J].Journal of Ginseng Research,2018,42(1):68-74.
[23]Lim T G,Jang M,Cho C W,et al.White ginseng extract induces immunomodulatory effects via the MKK4-JNK pathway[J].Food Science&Biotechnology,2016,25(6):1737-1744.
[24]Ueno H,Klechevsky E,Schmitt N,et al.Targeting human dendritic cell subsets for improved vaccines[J].Seminars Immunol,Academic Press,2011,23(1):21-27.
[25]Li J Y,Li J,Zhang F.The immunoregulatory effects of Chinese herbal medicine on the maturation and function of dendritic cells[J].J Ethnopharmacol,2015,171:184-195.
[26]王毅,郝钰,邱全瑛,等.人参皂苷Rg1与Rh1对树突状细胞表达HLA-DR、CD25、CD44、CD54、CD11c及E-selectin的影响[J].中国免疫学杂志,2007,(1):46-48,52.
[27]Takei M,Tachikawa E,Hasegawa H,et al.Dendritic cells maturation promoted by M1 and M4,end products of steroidal ginseng saponins metabolized in digestive tracts,drive a potent Th1 polarization[J].Biochemical Pharmacology,2004,68(3):441-452.
[28]Tung N H,Quang T H,Son J H,et al.Inhibitory effect of ginsenosides from steamed ginseng-leaves and flowers on the LPS-stimulated IL-12 production in bone marrow-derived dendritic cells[J].Archives of Pharmacal Research,2011,34(4):681-685.
[29]孙宏伟,王守岩,吴素琴,等.不同产地人参对小鼠NK细胞活性影响随机对照研究[J].实用中医内科杂志,2012,26(4):4-5.
[30]Sun Y,Guo M,Feng Y,et al.Effect of ginseng polysaccharides on NK cell cytotoxicity in immunosuppressed mice[J].Experimental and Therapeutic Medicine,2016,12(6):3773-3777.
[31]Shin M S,Hwang S H,Yoon T J,et al.Polysaccharides from ginseng leaves inhibit tumor metastasis via macrophage and NK cell activation[J].International Journal of Biological Macromolecules,2017,103:1327-1333.
[32]Kim Y J,Chung J W,Lee S J,et al.Progression from chronic atrophic gastritis to gastric cancer;tangle,toggle,tackle with Korea red ginseng[J].Journal of Clinical Biochemistry and Nutrition,2010,46(3):195-204.
[33]Zhang C,Xu W,Chen J,et al.Soybean oil containing ginseng saponins as adjuvants promotes production of cytokines and enhances immune responses to foot-and-mouth disease vaccine[J].Microbiology and Immunology,2017,62(3):187-194.
[34]Yang Z,Chen A,Sun H,et al.Ginsenoside Rd elicits Th1 and Th2 immune responses to ovalbumin in mice[J].Vaccine,2007,25(1):161-169.
[35]Hong C E,Lyu S Y.Anti-inflammatory and anti-oxidative effects of Korean red ginseng extract in human keratinocytes[J].Immune Network,2011,11(1):42-49.
[36]Vinh L B,Lee Y,Han Y K,et al.Two new dammarane-type triterpene saponins from Korean red ginseng and their anti-inflammatory effects[J].Bioorganic&Medicinal Chemistry Letters,2017,27(23):5149-5153.
[37]Yang Y,Yang W S,Yu T,et al.ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract[J].Journal of Ethnopharmacology,2014,154(1):218-228.
[38]Qu D F,Yu H J,Liu Z,et al.Ginsenoside Rg1 enhances immune response induced by recombinant Toxoplasma gondii SAG1antigen[J].Veterinary Parasitology,2011,179(1):28-34.
[39]储岳峰,颜新敏,胡元亮,等.几种中药成分的免疫增强活性及其作用效果[J].中国兽医科技,2005,35(1):67-70.
[40]Yu J,Shi F S,Hu S.Improved immune responses to a bivalent vaccine of Newcastle disease and avian influenza in chickens by ginseng stem-leaf saponins[J].Veterinary Immunology and Immunopathology,2015,167(3-4):147-155.
[41]Yu X,Zhang N,Lin W,et al.Regulatory effects of four ginsenoside monomers in humoral immunity of systemic lupus erythematosus[J].Experimental and Therapeutic Medicine,2018,15(2):2097-2103.
[42]Behrens G,Li M,Smith C M,et al.Helper T cells,dendritic cells and CTL Immunity[J].Immunology and Cell Biology,2004,82(1):84-90.
[43]Russell J H,Ley T J.Lymphocyte-mediated cytotoxicity[J].Annual Review of Immunology,2002,20(1):323-370.
[44]See D M,Broumand N,Sahl L,et al.In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients[J].Immunopharmacology,1997,35(3):229-235.
[45]Kenarova B,Neychev H,Hadjiivanova C,et al.Immunomodulating activity of ginsenoside Rg1 from Panax ginseng[J].The Japanese Journal of Pharmacology,1990,54(4):447-454.
[46]Lee H,Lee S,Jeong D,et al.Ginsenoside Rh2 epigenetically regulates cell-mediated immune pathway to inhibit proliferation of MCF-7 breast cancer cells[J].Journal of Ginseng Research,2018,42(4):455-462.
[2]陈霁,屈志炜,许琳,等.人参皂甙Re对多种记忆障碍的改善作用及对海马齿状回LTP的影响[C]//.中国药理学会补益药药理专业委员会.中国药理学会补益药药理专业委员会成立大会暨人参及补益药学术研讨会会议论文集.北京:中国药理学会,2011:2.
[3]许慧.人参皂苷Rgl及其代谢产物Rhl,Ppt生精保护作用的分子机制研究[D].开封:河南大学,2013.
[4]姚根兰,张娅萍,欧阳柳凤,等.人参抗疲劳作用的研究进展[J].世界中西医结合杂志,2015,10(8):1174-1177.
[5]潘鑫鑫,郑卫红.人参总皂甙抗衰老作用的实验研究[J].中国老年学杂志,1995,15(5):288-290.
[6]Song J H,hoi H J,Song H H,et al.Antiviral activity of ginsenosides against coxsackievirus B3,enterovirus 71,and human rhinovirus 3[J].Journal of Ginseng Research,2014,38(3):173-179.
[7]张南,李娜,李佳琳,等.人参、刺五加提取物对链脲佐菌素诱导糖尿病小鼠的降糖作用研究[J].天然产物研究与开发,2014,26(10):1690-1695.
[8]Wang Y,Liu Y,Zhang X Y,et al.Ginsenoside Rg1 regulates innate immune responses in macrophages through differentially modulating the NF-B and PI3K/Akt/mTOR pathways[J].International Immunopharmacology,2014,23(1):77-84.
[9]Singh V K,George C X,Singh N,et al.Combined treatment of mice with Panax ginseng extract and interferon inducer[J].Planta Medica,1983,47(4):234-236.
[10]Singh V K,Agarwal S S,Gupta B M.Immunomodulatory activity of Panax ginseng extract[J].Planta Medica,1984,50(6):462-465.
[11]Ackerknecht E H,Haushofer L.A short history of medicine[M].Maryland:JHU Press,2016.
[12]吴皓,林洪生,裴迎霞,等.人参皂甙Rg3对荷瘤及环磷酰胺化疗小鼠黏膜免疫力影响[J].中国肿瘤,2006,(6):369-371.
[13]刘艳艳,张凯,关家伟,等.人参皂苷对BALB/c小鼠肠道菌群的影响[J].现代生物医学进展,2015,(6):1041-1045.
[14]刘伟宏,龚守良.人参三醇组甙对雄性大鼠免疫器官的辐射防护作用[J].白求恩医科大学学报,1994,20(1):32-34.
[15]王庭富,孟正木.人参皂甙Rg3对免疫功能的影响[J].中国药科大学学报,1999,(2):55-57.
[16]Gordon S.The macrophage[J].Bioessays,1995,17(11):977-986.
[17]Medzhitov R,Janeway C A.Innate immunity:impact on the adaptive immune response[J].Current Opinion in Immunology,1997,9(1):4-9.
[18]Guzik T,Korbut R,Adamek-Guzik T.Nitric oxide and superoxide in inflammation[J].Physiol Pharmacol,2003,54(4):469-487.
[19]张才军,郭民,柳波,等.人参皂苷Rh1对免疫功能降低小鼠的免疫调节作用研究[J].昆明医学院学报,2009,30(11):51-54,58.
[20]管蓓蓓,曹丽,朱昌来,等.人参皂苷对巨噬细胞超微结构及MHC-II表达的影响[J].中国交通医学杂志,2008,22(3):218-220.
[21]Baek K S,Yi Y S,Son Y J,et al.In vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components[J].Journal of Ginseng Research,2016,40(4):437-444.
[22]Kang S,Park S J,Lee A Y,et al.Ginsenoside Rg3 promotes inflammation resolution through M2 macrophage polarization[J].Journal of Ginseng Research,2018,42(1):68-74.
[23]Lim T G,Jang M,Cho C W,et al.White ginseng extract induces immunomodulatory effects via the MKK4-JNK pathway[J].Food Science&Biotechnology,2016,25(6):1737-1744.
[24]Ueno H,Klechevsky E,Schmitt N,et al.Targeting human dendritic cell subsets for improved vaccines[J].Seminars Immunol,Academic Press,2011,23(1):21-27.
[25]Li J Y,Li J,Zhang F.The immunoregulatory effects of Chinese herbal medicine on the maturation and function of dendritic cells[J].J Ethnopharmacol,2015,171:184-195.
[26]王毅,郝钰,邱全瑛,等.人参皂苷Rg1与Rh1对树突状细胞表达HLA-DR、CD25、CD44、CD54、CD11c及E-selectin的影响[J].中国免疫学杂志,2007,(1):46-48,52.
[27]Takei M,Tachikawa E,Hasegawa H,et al.Dendritic cells maturation promoted by M1 and M4,end products of steroidal ginseng saponins metabolized in digestive tracts,drive a potent Th1 polarization[J].Biochemical Pharmacology,2004,68(3):441-452.
[28]Tung N H,Quang T H,Son J H,et al.Inhibitory effect of ginsenosides from steamed ginseng-leaves and flowers on the LPS-stimulated IL-12 production in bone marrow-derived dendritic cells[J].Archives of Pharmacal Research,2011,34(4):681-685.
[29]孙宏伟,王守岩,吴素琴,等.不同产地人参对小鼠NK细胞活性影响随机对照研究[J].实用中医内科杂志,2012,26(4):4-5.
[30]Sun Y,Guo M,Feng Y,et al.Effect of ginseng polysaccharides on NK cell cytotoxicity in immunosuppressed mice[J].Experimental and Therapeutic Medicine,2016,12(6):3773-3777.
[31]Shin M S,Hwang S H,Yoon T J,et al.Polysaccharides from ginseng leaves inhibit tumor metastasis via macrophage and NK cell activation[J].International Journal of Biological Macromolecules,2017,103:1327-1333.
[32]Kim Y J,Chung J W,Lee S J,et al.Progression from chronic atrophic gastritis to gastric cancer;tangle,toggle,tackle with Korea red ginseng[J].Journal of Clinical Biochemistry and Nutrition,2010,46(3):195-204.
[33]Zhang C,Xu W,Chen J,et al.Soybean oil containing ginseng saponins as adjuvants promotes production of cytokines and enhances immune responses to foot-and-mouth disease vaccine[J].Microbiology and Immunology,2017,62(3):187-194.
[34]Yang Z,Chen A,Sun H,et al.Ginsenoside Rd elicits Th1 and Th2 immune responses to ovalbumin in mice[J].Vaccine,2007,25(1):161-169.
[35]Hong C E,Lyu S Y.Anti-inflammatory and anti-oxidative effects of Korean red ginseng extract in human keratinocytes[J].Immune Network,2011,11(1):42-49.
[36]Vinh L B,Lee Y,Han Y K,et al.Two new dammarane-type triterpene saponins from Korean red ginseng and their anti-inflammatory effects[J].Bioorganic&Medicinal Chemistry Letters,2017,27(23):5149-5153.
[37]Yang Y,Yang W S,Yu T,et al.ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract[J].Journal of Ethnopharmacology,2014,154(1):218-228.
[38]Qu D F,Yu H J,Liu Z,et al.Ginsenoside Rg1 enhances immune response induced by recombinant Toxoplasma gondii SAG1antigen[J].Veterinary Parasitology,2011,179(1):28-34.
[39]储岳峰,颜新敏,胡元亮,等.几种中药成分的免疫增强活性及其作用效果[J].中国兽医科技,2005,35(1):67-70.
[40]Yu J,Shi F S,Hu S.Improved immune responses to a bivalent vaccine of Newcastle disease and avian influenza in chickens by ginseng stem-leaf saponins[J].Veterinary Immunology and Immunopathology,2015,167(3-4):147-155.
[41]Yu X,Zhang N,Lin W,et al.Regulatory effects of four ginsenoside monomers in humoral immunity of systemic lupus erythematosus[J].Experimental and Therapeutic Medicine,2018,15(2):2097-2103.
[42]Behrens G,Li M,Smith C M,et al.Helper T cells,dendritic cells and CTL Immunity[J].Immunology and Cell Biology,2004,82(1):84-90.
[43]Russell J H,Ley T J.Lymphocyte-mediated cytotoxicity[J].Annual Review of Immunology,2002,20(1):323-370.
[44]See D M,Broumand N,Sahl L,et al.In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients[J].Immunopharmacology,1997,35(3):229-235.
[45]Kenarova B,Neychev H,Hadjiivanova C,et al.Immunomodulating activity of ginsenoside Rg1 from Panax ginseng[J].The Japanese Journal of Pharmacology,1990,54(4):447-454.
[46]Lee H,Lee S,Jeong D,et al.Ginsenoside Rh2 epigenetically regulates cell-mediated immune pathway to inhibit proliferation of MCF-7 breast cancer cells[J].Journal of Ginseng Research,2018,42(4):455-462.