虫草素药理作用研究进展
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摘要
虫草素是我国传统医药冬虫夏草和蛹虫草的有效成分之一,具有抗菌抗炎、抗肿瘤、免疫调节和抗氧化等作用。还可以用于治疗肺部、肾脏和胃部等疾病,又可用作营养补充剂。随着研究的深入,虫草素的药理作用逐渐被挖掘出来,其作用机制也是逐渐清晰。本文整理了近年来关于虫草素的抗肿瘤、抗菌、抗炎、免疫调节、抗氧化和神经保护与调节等药理作用的最新进展,并加以总结。为后续更加深入地研究虫草素的药理作用奠定了基础。
Cordycepin is one of the active ingredients of traditional Chinese medicine Cordyceps sinensis and Cordyceps militaris. It has antibacterial,antiinflammatory,antitumor,immune regulation and anti-oxidation effects. It can also be used to treat diseases such as the lungs,kidneys and stomach. And it can also be used as a nutritional supplement. With the deepening of research,the pharmacological effects of cordycepin have been gradually excavated,and its mechanism of action has gradually become clear. In this paper,recent advances in the pharmacological effects of cordycepin against anti-tumor,anti-bacterial,anti-inflammatory,immunomodulatory,anti-oxidative and neuroprotective,and regulatory were reviewed and summarized. It laid a foundation for further study on the role of cordycepin pharmacology.
Cordycepin is one of the active ingredients of traditional Chinese medicine Cordyceps sinensis and Cordyceps militaris. It has antibacterial,antiinflammatory,antitumor,immune regulation and anti-oxidation effects. It can also be used to treat diseases such as the lungs,kidneys and stomach. And it can also be used as a nutritional supplement. With the deepening of research,the pharmacological effects of cordycepin have been gradually excavated,and its mechanism of action has gradually become clear. In this paper,recent advances in the pharmacological effects of cordycepin against anti-tumor,anti-bacterial,anti-inflammatory,immunomodulatory,anti-oxidative and neuroprotective,and regulatory were reviewed and summarized. It laid a foundation for further study on the role of cordycepin pharmacology.
引文
[1]Cleaver J H M.Medicinal value of the caterpillar fungi species of the genus cordyceps(Fr)link(Ascomycetes):A review[J].Med Mushrooms,2008,10:219-234.
[2]Yang W S,Nam G S,Kim M Y,et al.Syk-mediated suppression of inflammatory responses by Cordyceps bassiana[J].The American Journal of Chinese Medicine,2017,45(6):1217-1232.
[3]Zhong J J,Xiao J H.Secondary metabolites from medicinal higher fungi[J].Advances in Biochemical Engineering Biotechnology,2009,113(113):79.
[4]Russell R,Paterson M.Cordyceps-a traditional Chinese medicine and another fungal the rapeutic biofactory[J].Phytochemistry,2008,69:1469-1495.
[5]Wu W D,Hu Z M,Shang M J,et al.Cordycepin down-regulates multiple drug resistant(MDR)/HIF-1α through regulating AMPK/m TORC1 signaling in GBC-SD gallbladder cancer cells[J].Int J Mol Sci,2014,15(7):12778-12790.
[6]王延明.九州虫草基因组改组育种与体外抗氧化活性研究[D].济南:山东大学,2013.
[7]李晖,孙佳瑜,廖康汉,等.虫草素抗炎作用及机制研究[J].天津中医药,2016,33(5):303-306.
[8]王征,武雪,刘建利,等.虫草素抗肿瘤活性研究进展[J].中国药学杂志,2015,50(16):1365-1368.
[9]陈丽冰,吴光旭,程薇,等.北虫草培养残基中虫草素的提取纯化及抗肿瘤活性[J].食品科学技术学报,2016,34(4):73-79.
[10]李兵,张文成,付传香,等.蛹虫草中虫草素及腺苷对糖尿病小鼠肾脏氧化应激的影响[J].世界最新医学信息文摘:连续型电子期刊,2016,57(16):1-3.
[11]Kinoshita T,Nakanishi I,Terasaka T,et al.Structural basis of compound recognition by adenosine deaminase[J].Biochemistry,2005,44(31):10562.
[12]Gillerman I,Fischer B.Investigations into the origin of the molecular recognition of several adenosine deaminase inhibitors[J].Journal of Medicinal Chemistry,2011,54(1):107-21.
[13]Chiu C P,Liu S C,Tang C H,et al.Anti-inflammatory cerebrosides from cultivated Cordyceps militaris[J].Journal of Agricultural & Food Chemistry,2016,64(7):1540.
[14]Yang X,Li Y,He Y,et al.Cordycepin alleviates airway hyperreactivity in a murine model of asthma by attenuating the inflammatory process[J].Int Immunopharmacol,2015,26(2):401-408.
[15]邓昌,欧阳波,陶然,等.虫草素对小鼠脑缺血再灌注损伤的神经保护作用及炎症调节[J].中国老年学,2014,34(3):687-690.
[16]苏岩.虫草素调血脂作用与上调AMPK 蛋白表达作用机制研究[D].哈尔滨:哈尔滨商业大学,2013.
[17]Cunningham K G,Hutchinson S A,Manson W,et al.Cordycepin,a metabolic product from cultures Cordyceps militaris Link Part I.Isolation and characterization[J].Journal of the Chemical Society,1951,2:2299-2300.
[18]Li D G.,Ren Z X.Cordyceps sinensis promotes immune regulation and enhances bacteriostatic activity of PA-824 via IL-10 in Mycobacterium tuberculosis disease[J].Brazilian Journal of Medical and Biological Research 2017,50(9):6188
[19]韦会平,叶小利,张华英,等.通过化学结构修饰提高虫草素抗菌活性的试验研究[J].天然产物研究与开发,2010(22):29-32.
[20]Vodnala S K,Lundb?ck T,Yeheskieli E,et al.Structure-activity relationships of synthetic cordycepin analogues as experimental therapeutics for African trypanosomiasis[J].Journal of Medicinal Chemistry,2013,56(24):9861-73.
[21]刘阳,王雅玲,袁思杨,等.优化蛹虫草浸提条件对金黄色葡萄球菌的控制效果[J].食品工业科技,2011,32(4):139-142.
[22]Park J G,Cho J Y,Sung G H,et al.Anticancer efficacy of Cordyceps militaris ethanol extract in a xenografted leukemia model[J].Evidence-Based Complementray and Alternative Medicine,2017.
[23]Kim Y S,Kim E K,Hwang J W,et al.Fermented Asterina pectinifera with cordyceps militaris mycelia induced apoptosis in B16F10 melanoma cells[J].Advances in Experimental Medicine and Biology,2017,975(2):1141.
[24]田忠林,赵克明,李季泓.虫草素抑制Ras蛋白表达并诱导非小细胞肺癌H358细胞凋亡研究[J].中华中医药学刊,2016(5):1237-1239.
[25]Mingwei C,Hui R,Tian Y,et al.Pro-apoptotic effects of Paecilomyces hepiali,a Cordyceps sinensis extract on human lung adenocarcinoma A549 cells in vitro[J].Journal of Cancer Research and Therapeutics,2011,7(4):421.
[26]Pao H Y,Pan B S,Leu S F,et al.Cordycepin stimulated steroidogenesis in ma-10 mouse leydig tumor cells through the protein kinase C pathway[J].J Agric Food Chem,2012,60(19):4905-4913.
[27]Chen Y,Chen Y C,Lin Y T,et al.Cordycepin induces apoptosis of CGTH W-2 thyroid carcinoma cells through the calcium-calpain-caspase 7-PARP pathway[J].Journal of Agricultural & Food Chemistry,2010,58(22):11645-11652.
[28]Aramwit P,Porasuphatana S,Srichana T,et al.Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity[J].Nanoscale Research Letters,2015,10(1):152.
[29]Yifan L I,Rong L I,Zhu S,et al.Cordycepin induces apoptosis and autophagy in human neuroblastoma SK-N-SH and BE(2)-M17 cells[J].Oncology Letters,2015,9(6):2541.
[30]Chen Y H,Wang J Y,Pan B S,et al.Cordycepin enhances cisplatin apoptotic effect through caspase/MAPK pathways in human head and neck tumor cells[J].Oncotargets & Therapy,2013,6:983-998.
[31]陈琴,姜新,顾欣霞,等.虫草素对鱼藤酮诱导PC12细胞凋亡的保护作用[J].中国药理学通报,2015(11):68.
[32]高青,龙军,简立信,等.复方蛹虫草颗粒对小鼠免疫功能以及脾淋巴细胞增殖的影响[J].中国实验方剂学杂志,2013,19(16):259-263.
[33]孙勇,杨文建,马宁,等.蛹虫草子实体超细粉对小鼠免疫力及抗氧化功能的调节作用[J].食用菌药报,2013,20(1):66-69.
[34]左克源,裘军,李维亮,等.人工蛹虫草子实体对小鼠免疫功能的影响[J].医药导报,2007,26(3):227-229.
[35]程俊丽,马玉良,冯翠萍.北虫草和北虫草根成分测定及水提液的抗氧化活性[J].中国药物与临床,2014(5):602-604.
[36]Olatunji O J,Feng Y,Olatunji O O,et al.Cordycepin protects PC12 cells against 6-hydroxydopamine induced neurotoxicity via its antioxidant properties[J].Biomedicine & Pharmacotherapy,2016,81:7.
[37]Jin M L,Park S Y,Kim Y H,et al.The neuroprotective effects of cordycepin inhibit glutamate-induced oxidative and ER stress-associated apoptosis in hippocampal HT22 cells[J].Neurotoxicology,2014,41(3):102-111.
[38]Chen C,Liu X P,Jiang W,et al.Anti-effects of cordycepin to hypoxia-induced membrane depolarization on hippocampal CA1 pyramidal neuron[J].European Journal of Pharmacology,2016,796:1-6.
[39]Cheng Y,Wei Y,Yang W,et al.Cordycepin confers neuroprotection in mice models of intracerebral hemorrhage via suppressing NLRP3 inflammasome activation[J].Metabolic Brain Disease,2017,32(4):1-13.
[40]孟雪莲,陈长兰,孔维娟,等.虫草素抑制脂多糖诱导的小胶质细胞活化及神经保护作用[J].食品科学,2014,35(19):224-230.
[41]Jung K D,Hwan K Y,Kon K K,et al.Increased glucose metabolism and alpha-glucosidase inhibition in Cordyceps militaris water extract-treated HepG2 cells[J].Nutrition Research and Practice,2017,11(3):180-189.
[42]王洪军,李艳芳,孙克妍,等.北虫草提取物影响去势大鼠附性腺与血清睾酮的实验研究[J].解放军药学学报,2009,25(4):323-325.
[43]Goubran H A,Burnouf T.Platelets,Coagulation and cancer:Multifaceted interactions[J].American Medical Journal,2012,3:130-140.
[44]Ko B S,Lu Y J,Yao W L,et al.Cordycepin Regulates GSK-3?2/?2-catenin signaling in human leukemia cells[J].PLoS ONE,2013,8(9):e76320.
[45]韦会平.虫草素的生物合成及化学结构修饰[D].重庆:西南大学,2009.
[2]Yang W S,Nam G S,Kim M Y,et al.Syk-mediated suppression of inflammatory responses by Cordyceps bassiana[J].The American Journal of Chinese Medicine,2017,45(6):1217-1232.
[3]Zhong J J,Xiao J H.Secondary metabolites from medicinal higher fungi[J].Advances in Biochemical Engineering Biotechnology,2009,113(113):79.
[4]Russell R,Paterson M.Cordyceps-a traditional Chinese medicine and another fungal the rapeutic biofactory[J].Phytochemistry,2008,69:1469-1495.
[5]Wu W D,Hu Z M,Shang M J,et al.Cordycepin down-regulates multiple drug resistant(MDR)/HIF-1α through regulating AMPK/m TORC1 signaling in GBC-SD gallbladder cancer cells[J].Int J Mol Sci,2014,15(7):12778-12790.
[6]王延明.九州虫草基因组改组育种与体外抗氧化活性研究[D].济南:山东大学,2013.
[7]李晖,孙佳瑜,廖康汉,等.虫草素抗炎作用及机制研究[J].天津中医药,2016,33(5):303-306.
[8]王征,武雪,刘建利,等.虫草素抗肿瘤活性研究进展[J].中国药学杂志,2015,50(16):1365-1368.
[9]陈丽冰,吴光旭,程薇,等.北虫草培养残基中虫草素的提取纯化及抗肿瘤活性[J].食品科学技术学报,2016,34(4):73-79.
[10]李兵,张文成,付传香,等.蛹虫草中虫草素及腺苷对糖尿病小鼠肾脏氧化应激的影响[J].世界最新医学信息文摘:连续型电子期刊,2016,57(16):1-3.
[11]Kinoshita T,Nakanishi I,Terasaka T,et al.Structural basis of compound recognition by adenosine deaminase[J].Biochemistry,2005,44(31):10562.
[12]Gillerman I,Fischer B.Investigations into the origin of the molecular recognition of several adenosine deaminase inhibitors[J].Journal of Medicinal Chemistry,2011,54(1):107-21.
[13]Chiu C P,Liu S C,Tang C H,et al.Anti-inflammatory cerebrosides from cultivated Cordyceps militaris[J].Journal of Agricultural & Food Chemistry,2016,64(7):1540.
[14]Yang X,Li Y,He Y,et al.Cordycepin alleviates airway hyperreactivity in a murine model of asthma by attenuating the inflammatory process[J].Int Immunopharmacol,2015,26(2):401-408.
[15]邓昌,欧阳波,陶然,等.虫草素对小鼠脑缺血再灌注损伤的神经保护作用及炎症调节[J].中国老年学,2014,34(3):687-690.
[16]苏岩.虫草素调血脂作用与上调AMPK 蛋白表达作用机制研究[D].哈尔滨:哈尔滨商业大学,2013.
[17]Cunningham K G,Hutchinson S A,Manson W,et al.Cordycepin,a metabolic product from cultures Cordyceps militaris Link Part I.Isolation and characterization[J].Journal of the Chemical Society,1951,2:2299-2300.
[18]Li D G.,Ren Z X.Cordyceps sinensis promotes immune regulation and enhances bacteriostatic activity of PA-824 via IL-10 in Mycobacterium tuberculosis disease[J].Brazilian Journal of Medical and Biological Research 2017,50(9):6188
[19]韦会平,叶小利,张华英,等.通过化学结构修饰提高虫草素抗菌活性的试验研究[J].天然产物研究与开发,2010(22):29-32.
[20]Vodnala S K,Lundb?ck T,Yeheskieli E,et al.Structure-activity relationships of synthetic cordycepin analogues as experimental therapeutics for African trypanosomiasis[J].Journal of Medicinal Chemistry,2013,56(24):9861-73.
[21]刘阳,王雅玲,袁思杨,等.优化蛹虫草浸提条件对金黄色葡萄球菌的控制效果[J].食品工业科技,2011,32(4):139-142.
[22]Park J G,Cho J Y,Sung G H,et al.Anticancer efficacy of Cordyceps militaris ethanol extract in a xenografted leukemia model[J].Evidence-Based Complementray and Alternative Medicine,2017.
[23]Kim Y S,Kim E K,Hwang J W,et al.Fermented Asterina pectinifera with cordyceps militaris mycelia induced apoptosis in B16F10 melanoma cells[J].Advances in Experimental Medicine and Biology,2017,975(2):1141.
[24]田忠林,赵克明,李季泓.虫草素抑制Ras蛋白表达并诱导非小细胞肺癌H358细胞凋亡研究[J].中华中医药学刊,2016(5):1237-1239.
[25]Mingwei C,Hui R,Tian Y,et al.Pro-apoptotic effects of Paecilomyces hepiali,a Cordyceps sinensis extract on human lung adenocarcinoma A549 cells in vitro[J].Journal of Cancer Research and Therapeutics,2011,7(4):421.
[26]Pao H Y,Pan B S,Leu S F,et al.Cordycepin stimulated steroidogenesis in ma-10 mouse leydig tumor cells through the protein kinase C pathway[J].J Agric Food Chem,2012,60(19):4905-4913.
[27]Chen Y,Chen Y C,Lin Y T,et al.Cordycepin induces apoptosis of CGTH W-2 thyroid carcinoma cells through the calcium-calpain-caspase 7-PARP pathway[J].Journal of Agricultural & Food Chemistry,2010,58(22):11645-11652.
[28]Aramwit P,Porasuphatana S,Srichana T,et al.Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity[J].Nanoscale Research Letters,2015,10(1):152.
[29]Yifan L I,Rong L I,Zhu S,et al.Cordycepin induces apoptosis and autophagy in human neuroblastoma SK-N-SH and BE(2)-M17 cells[J].Oncology Letters,2015,9(6):2541.
[30]Chen Y H,Wang J Y,Pan B S,et al.Cordycepin enhances cisplatin apoptotic effect through caspase/MAPK pathways in human head and neck tumor cells[J].Oncotargets & Therapy,2013,6:983-998.
[31]陈琴,姜新,顾欣霞,等.虫草素对鱼藤酮诱导PC12细胞凋亡的保护作用[J].中国药理学通报,2015(11):68.
[32]高青,龙军,简立信,等.复方蛹虫草颗粒对小鼠免疫功能以及脾淋巴细胞增殖的影响[J].中国实验方剂学杂志,2013,19(16):259-263.
[33]孙勇,杨文建,马宁,等.蛹虫草子实体超细粉对小鼠免疫力及抗氧化功能的调节作用[J].食用菌药报,2013,20(1):66-69.
[34]左克源,裘军,李维亮,等.人工蛹虫草子实体对小鼠免疫功能的影响[J].医药导报,2007,26(3):227-229.
[35]程俊丽,马玉良,冯翠萍.北虫草和北虫草根成分测定及水提液的抗氧化活性[J].中国药物与临床,2014(5):602-604.
[36]Olatunji O J,Feng Y,Olatunji O O,et al.Cordycepin protects PC12 cells against 6-hydroxydopamine induced neurotoxicity via its antioxidant properties[J].Biomedicine & Pharmacotherapy,2016,81:7.
[37]Jin M L,Park S Y,Kim Y H,et al.The neuroprotective effects of cordycepin inhibit glutamate-induced oxidative and ER stress-associated apoptosis in hippocampal HT22 cells[J].Neurotoxicology,2014,41(3):102-111.
[38]Chen C,Liu X P,Jiang W,et al.Anti-effects of cordycepin to hypoxia-induced membrane depolarization on hippocampal CA1 pyramidal neuron[J].European Journal of Pharmacology,2016,796:1-6.
[39]Cheng Y,Wei Y,Yang W,et al.Cordycepin confers neuroprotection in mice models of intracerebral hemorrhage via suppressing NLRP3 inflammasome activation[J].Metabolic Brain Disease,2017,32(4):1-13.
[40]孟雪莲,陈长兰,孔维娟,等.虫草素抑制脂多糖诱导的小胶质细胞活化及神经保护作用[J].食品科学,2014,35(19):224-230.
[41]Jung K D,Hwan K Y,Kon K K,et al.Increased glucose metabolism and alpha-glucosidase inhibition in Cordyceps militaris water extract-treated HepG2 cells[J].Nutrition Research and Practice,2017,11(3):180-189.
[42]王洪军,李艳芳,孙克妍,等.北虫草提取物影响去势大鼠附性腺与血清睾酮的实验研究[J].解放军药学学报,2009,25(4):323-325.
[43]Goubran H A,Burnouf T.Platelets,Coagulation and cancer:Multifaceted interactions[J].American Medical Journal,2012,3:130-140.
[44]Ko B S,Lu Y J,Yao W L,et al.Cordycepin Regulates GSK-3?2/?2-catenin signaling in human leukemia cells[J].PLoS ONE,2013,8(9):e76320.
[45]韦会平.虫草素的生物合成及化学结构修饰[D].重庆:西南大学,2009.