莲子心生物碱活性成分的药理作用研究进展
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摘要
莲子心中的生物碱类活性成分主要有莲心碱、异莲心碱、甲基莲心碱等,具有一系列药用价值和保健功能,如抗癌、降血压、抗心律失常、抗氧化和清除自由基、抗纤维化、抗代谢综合征、神经保护及抗炎等.文章对莲子心生物碱的药理作用研究进展进行综述,为进一步研究莲子心生物碱的药用价值及合理开发利用提供依据.
The main alkaloids inlotus plumule include liensinine,isoliensinine,and neferine,which have a series of medicinal value and health function,such as anticarcinogenesis,anti-hypertension,anti-arrhythmia,antioxidation,free radical scavenging activity,anti-fibrosis,anti-metabolic syndrome,neuroprotection,and anti-inflammation.This article summarizes the pharmacological effects of alkaloids from lotus plumule,which may help to lay a foundation for future studies on their medicinal value and rational development and utilization.
The main alkaloids inlotus plumule include liensinine,isoliensinine,and neferine,which have a series of medicinal value and health function,such as anticarcinogenesis,anti-hypertension,anti-arrhythmia,antioxidation,free radical scavenging activity,anti-fibrosis,anti-metabolic syndrome,neuroprotection,and anti-inflammation.This article summarizes the pharmacological effects of alkaloids from lotus plumule,which may help to lay a foundation for future studies on their medicinal value and rational development and utilization.
引文
[1] 李文阳,杨世平,何平均.莲心保健茶的研制[J].湖南农业科学,2000,3:56.
[2] 中国药典一部,1990版.248.
[3] Tomita M,Furukawa H,Yang TH,et al.On the alkaloids of NelumbonuciferaGaertn.8.Studies on the alkaloids of loti embryo.1.Structure of isoliensinine,a new biscoclaurine type alkaloid[J].Chem Pharm Bull(Tokyo),1965,13(1):39-43.
[4] 潘竞先,陆军,张建军,等.莲子心钙拮抗活性成分的研究[J].北京大学学报(医学版),1989,21(5):401-403.
[5] Wang J,Hu X,Yin W,et al.Alkaloids of plumulanelumbinis[J].Zhong Guo Zhong Yao Za Zhi,1991,16(11):673-675,703.
[6] Erasto P,Omolo J,Sunguruma R,et al.Evaluation of antimycobacterial activity of higenamineusinggalleria mellonella as an in vivo infection model[J].Nat Prod Bioprospect,2018,8(1):63-69.
[7] Crestey F,Jensen A A,Borch M,et al.Design,synthesis,and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists[J].J Med Chem,2013,56(23):9673-9682.
[8] 李萍,杨光明,张玉玲,等.莲子心脂溶性生物碱的分离、鉴定[J].食品与生物技术学报,2016,35(1):19-27.
[9] Mukherjee P K,Mukherjee D,Maji A K,et al.The sacred lotus(Nelumbonucifera)-phytochemical and therapeutic profile[J].J Pharm Pharmacol,2009,61(4):407-422.
[10] 曾建伟,谢勇,林忠宁,等.莲子心抗肿瘤活性部位的筛选研究[J].实用中西医结合临床,2014,14(1):87-88.
[11] Zhang X,Wang X,Wu T,et al.Isoliensinine induces apoptosis in triple-negative human breast cancer cells through ROS generation and p38 MAPK/JNK activation[J].Sci Rep,2015,5(5):12579.
[12] 熊一力,王嘉陵,钱家庆.莲心碱对血管平滑肌细胞增殖及热应激蛋白70T和P53表达的影响[J].中国动脉硬化杂志,1997,5(1):23-26.
[13] Poornima P,Kumar V B,Weng C F,et al.Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima,A549 cells[J].Food Chem Toxicol,2014,68:87-98.
[14] 石书红,张辉,庄英帜,等.甲基莲心碱对长春新碱抑制人胃癌细胞增殖作用的影响[J].海南医学,2008,13(5):113-115.
[15] Zhang X,Liu Z,Xu B,et al.Neferine,an alkaloid ingredient in lotus seed embryo,inhibits proliferation of human osteosarcoma cells by promoting p38 MAPK-mediated p21 stabilization[J].Eur J Pharmacol,2012,677(1-3):47-54.
[16] 李娜,宋金春.甲基莲心碱对人肝星状细胞共培养条件下的人肝癌细胞中的转化生长因子(TGF-β1)的影响[J].中国医院药学杂志,2018,(2):157-160.
[17] Poornima P,Weng C F,Padma V V.Neferine from Nelumbo nucifera induces autophagy through the inhibition of PI3K/Akt/mTOR pathway and ROS hyper generation in A549 cells[J].Food Chem,2013,141(4):3598-3605.
[18] Xu L,Zhang X,Li Y,et al.Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation[J].Tumor Biol,2016,37(7):8721-8729.
[19] Shu G,Yue L,Zhao W,et al.Isoliensinine,a bioactive alkaloid derived from embryos of Nelumbo nucifera,Induces hepatocellular carcinoma cell apoptosis through suppression of NF-κB signaling[J].J Agric Food Chem,2015,63(40):8793-8803.
[20] Shu G,Lang Z,Jiang S,et al.Isoliensinine induces dephosphorylation of NF-κB p65 subunit at Ser536 via a PP2A-dependent mechanism in hepatocellular carcinoma cells:roles of impairing PP2A/I2PP2A interaction[J].Oncotarget,2016,7(26):40285-40296.
[21] 胡文淑,郭莲军,冯秀玲,等.甲基莲心碱的降压作用[J].中国药理学与毒理学杂志,1990,4(2):107-110.
[22] 姚伟,朱铨英.粉防己碱和甲基莲心碱对大鼠离体胸主动脉[J].第二军医大学学报,1991,7(5):357-359.
[23] 王永信.甲基莲心碱对血管平滑肌α受体引起45Ca外溢与内流的影响[J].中国中药杂志,1996,29(2):117-118.
[24] 杨健,何文.莲心季胺碱药理作用研究[J].广东药学院学报,1999,15(3):183-185.
[25] 陆曙,潘扬,陶冉,等.莲心碱与莲心季铵碱对肾性高血压大鼠左室肥厚逆转作用的比较[J].南京中医药大学学报,2008,24(5):327-329.
[26] Xiao J H,Zhang Y L,Feng X L,et al.Effects of isoliensinine on angiotensin II-induced proliferation of porcine coronary arterial smooth muscle cells[J].J Asian Nat Prod Res,2006,8(3):209-216.
[27] 张京梅,李鹏跃,王岚,等.莲子心总生物碱的提取分离及药效学初步研究[J].中国实验方剂学杂志,2009,15(6):26-28.
[28] 王瑞芳,欧来良.莲子心提取物抗心律失常作用及其急性毒性研究[J].中草药,2008,39(3):413-415.
[29] Dong Z X,Zhao X,Gu D F,et al.Comparative effects of liensinine and neferine on the human ether-a-go-go-related gene potassium channel and pharmacological activity analysis[J].Cell PhysiolBiochem,2012,29(3-4):431-442.
[30] 王嘉陵,董登贤,王祖文,等.莲子心中4种生物碱抗心律失常作用的比较[J].中国药学杂志,1992,27(6):359.
[31] 陈默思,贾麟,费宇杰,等.异莲心碱对牵张性心律失常的作用[J].中国医院药学杂志,2006,26(6):658-661.
[32] Wan J,Zhao L,Xu C,et al.Effects of neferine on the pharmacokinetics of amiodarone in rats[J].Biomed Chromatogr,2011,25(8):858-866.
[33] 杨小青,宋金春,谢顺岚,等.莲子心中酚性与非酚性生物碱体外抗氧化活性比较[J].医药导报,2015,34(12):1579-1583.
[34] 杨小青,宋金春,谢顺岚,等.不同提取方法莲子心总生物碱抗氧化活性比较[J].中国医药导报,2015,12(18):100-104.
[35] 胡彩英,曾秋棠.甲基莲心碱对氧化低密度脂蛋白导致平滑肌细胞脂质堆积和增殖的影响[J].华中医学杂志,2006,30(5):401-403.
[36] 王辉,刘月,周本宏,等.甲基莲心碱对高脂血症模型大鼠的作用研究[J].中国药房,2006,17(13):974-976.
[37] 王辉,杨柳,杨俊,等.异莲心碱对大鼠肝匀浆脂质过氧化的影响[J].中国医院药学杂志,2005,25(5):402-404.
[38] Jung H A,Jin S E,Choi R J,et al.Anti-amnesic activity of neferine with antioxidant and anti-inflammatory capacities,as well as inhibition of ChEs and BACE1[J].Life Sci,2010,87(13-14):420-430.
[39] Xie Y,Zhang Y,Zhang L T,et al.Protective effects of alkaloid compounds from Nelumbinis Plumula on tert-butyl hydroperoxide-induced oxidative stress[J].Molecules,2013,18(9):10285-10300.
[40] Liu W,Yi D D,Guo J L,et al.Nuciferine,extracted from Nelumbo nucifera Gaertn,inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer[J].J Ethnopharmacol,2015,165:83-93.
[41] 高天娇,董蕾,史海涛,等.莲子心醇提物抗四氯化碳诱导大鼠肝纤维化的实验研究[J].中国中西医结合杂志,2014,34(12):1476-1480.
[42] Kinnula V L,Fattman C L,Tan R J,et al.Oxidative stress in pulmonary fibrosis:a possible role for redox modulatory therapy[J].Am J Respir Crit Care Med,2005,172(4):417-422.
[43] Xiao J H,Zhang J H,Chen H L,et al.Inhibitory effects of isoliensinine on bleomycin-induced pulmonary fibrosis in mice[J].Planta Med,2005,71(3):225-230.
[44] Zhao L,Wang X,Chang Q,et al.Neferine,a bisbenzylisoquinline alkaloid attenuates bleomycin-induced pulmonary fibrosis[J].Eur J Pharmacol,2010,627(1-3):304-312.
[45] 潘扬,尚文斌,王天山,等.莲子心及Nef对实验性糖尿病及肥胖大鼠模型的影响[J].南京中医药大学学报,2003,19(4):217-219.
[46] 刘双梅,李桂林,汤晓丽,等.甲基莲心碱对2型糖尿病模型大鼠作用的代谢组学研究[J].中国药理学通报,2012,28(4):490-495.
[47] Guan G,Han H,Yang Y,et al.Neferine prevented hyperglycemia-induced endothelial cell apoptosis through suppressing ROS/Akt/NF-κB signal[J].Endocrine,2014,47(3):764-771.
[48] Yang X,Huang M,Yang J,et al.Activity of isoliensinine in improving the symptoms of type 2 diabetic mice via activation of AMP-Activated kinase and regulation of PPARγ[J].J Agric Food Chem,2017,65(33):7168-7178.
[49] Je J Y,Lee D B.Nelumbonucifera leaves protect hydrogen peroxide-induced hepatic damage via antioxidant enzymes and HO-1/Nrf2 activation[J].Food Funct,2015,6(6):1911-1918.
[50] Farrell M S,Mccorvy J D,Huang X P,et al.In vitro and in vivo characterization of the alkaloid Nuciferine[J].PLoS One,2016,11(3):e0150602.
[51] Sugimoto Y,Nishimura K,Itoh A,et al.Serotonergic mechanisms are involved in antidepressant-like effects of bisbenzylisoquinolinesliensinine and its analogs isolated from the embryo of Nelumbo nucifera?Gaertner seeds in mice[J].J Pharm Pharmacol,2016,67(12):1716-1722.
[52] Meng X L,Zheng LC,Liu J,et al.Inhibitory effects of three bisbenzylisoquinoline alkaloids on lipopolysaccharide-induced microglial activation[J].Rsc Advances,2017,7(30):18347-18357.
[53] Peng Z Y,Zhang S D,Liu S,et al.Protective effect of neferine on endothelial cell nitric oxide production induced by lysophosphatidylcholine:the role of the DDAH-ADMA pathway[J].Can J PhysiolPharmacol,2011,89(4):289-294.
[54] Wang M,Liu Y,Yang Y,et al.Nuciferine restores potassium oxonate-induced hyperuricemia and kidney inflammation in mice[J].Eur J Pharmacol,2015,747:59-70.
[55] Yu J,Hu W S.Effects of neferine on platelet aggregation in rabbits[J].Yao Xue Xue Bao,1997,32(1):1-4.
[56] 陈灵骏,罗顺德.异莲心碱抗血小板聚集和抗凝血作用[J].中国医院药学杂志,2011,31(15):1257-1259.
[57] 张玉玲,杨光明,李萍,等.四种莲子心生物碱对H2O2诱导血管内皮细胞损伤的保护作用[J].中国生化药物杂志,2015,35(3):1-5.
[2] 中国药典一部,1990版.248.
[3] Tomita M,Furukawa H,Yang TH,et al.On the alkaloids of NelumbonuciferaGaertn.8.Studies on the alkaloids of loti embryo.1.Structure of isoliensinine,a new biscoclaurine type alkaloid[J].Chem Pharm Bull(Tokyo),1965,13(1):39-43.
[4] 潘竞先,陆军,张建军,等.莲子心钙拮抗活性成分的研究[J].北京大学学报(医学版),1989,21(5):401-403.
[5] Wang J,Hu X,Yin W,et al.Alkaloids of plumulanelumbinis[J].Zhong Guo Zhong Yao Za Zhi,1991,16(11):673-675,703.
[6] Erasto P,Omolo J,Sunguruma R,et al.Evaluation of antimycobacterial activity of higenamineusinggalleria mellonella as an in vivo infection model[J].Nat Prod Bioprospect,2018,8(1):63-69.
[7] Crestey F,Jensen A A,Borch M,et al.Design,synthesis,and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists[J].J Med Chem,2013,56(23):9673-9682.
[8] 李萍,杨光明,张玉玲,等.莲子心脂溶性生物碱的分离、鉴定[J].食品与生物技术学报,2016,35(1):19-27.
[9] Mukherjee P K,Mukherjee D,Maji A K,et al.The sacred lotus(Nelumbonucifera)-phytochemical and therapeutic profile[J].J Pharm Pharmacol,2009,61(4):407-422.
[10] 曾建伟,谢勇,林忠宁,等.莲子心抗肿瘤活性部位的筛选研究[J].实用中西医结合临床,2014,14(1):87-88.
[11] Zhang X,Wang X,Wu T,et al.Isoliensinine induces apoptosis in triple-negative human breast cancer cells through ROS generation and p38 MAPK/JNK activation[J].Sci Rep,2015,5(5):12579.
[12] 熊一力,王嘉陵,钱家庆.莲心碱对血管平滑肌细胞增殖及热应激蛋白70T和P53表达的影响[J].中国动脉硬化杂志,1997,5(1):23-26.
[13] Poornima P,Kumar V B,Weng C F,et al.Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima,A549 cells[J].Food Chem Toxicol,2014,68:87-98.
[14] 石书红,张辉,庄英帜,等.甲基莲心碱对长春新碱抑制人胃癌细胞增殖作用的影响[J].海南医学,2008,13(5):113-115.
[15] Zhang X,Liu Z,Xu B,et al.Neferine,an alkaloid ingredient in lotus seed embryo,inhibits proliferation of human osteosarcoma cells by promoting p38 MAPK-mediated p21 stabilization[J].Eur J Pharmacol,2012,677(1-3):47-54.
[16] 李娜,宋金春.甲基莲心碱对人肝星状细胞共培养条件下的人肝癌细胞中的转化生长因子(TGF-β1)的影响[J].中国医院药学杂志,2018,(2):157-160.
[17] Poornima P,Weng C F,Padma V V.Neferine from Nelumbo nucifera induces autophagy through the inhibition of PI3K/Akt/mTOR pathway and ROS hyper generation in A549 cells[J].Food Chem,2013,141(4):3598-3605.
[18] Xu L,Zhang X,Li Y,et al.Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation[J].Tumor Biol,2016,37(7):8721-8729.
[19] Shu G,Yue L,Zhao W,et al.Isoliensinine,a bioactive alkaloid derived from embryos of Nelumbo nucifera,Induces hepatocellular carcinoma cell apoptosis through suppression of NF-κB signaling[J].J Agric Food Chem,2015,63(40):8793-8803.
[20] Shu G,Lang Z,Jiang S,et al.Isoliensinine induces dephosphorylation of NF-κB p65 subunit at Ser536 via a PP2A-dependent mechanism in hepatocellular carcinoma cells:roles of impairing PP2A/I2PP2A interaction[J].Oncotarget,2016,7(26):40285-40296.
[21] 胡文淑,郭莲军,冯秀玲,等.甲基莲心碱的降压作用[J].中国药理学与毒理学杂志,1990,4(2):107-110.
[22] 姚伟,朱铨英.粉防己碱和甲基莲心碱对大鼠离体胸主动脉[J].第二军医大学学报,1991,7(5):357-359.
[23] 王永信.甲基莲心碱对血管平滑肌α受体引起45Ca外溢与内流的影响[J].中国中药杂志,1996,29(2):117-118.
[24] 杨健,何文.莲心季胺碱药理作用研究[J].广东药学院学报,1999,15(3):183-185.
[25] 陆曙,潘扬,陶冉,等.莲心碱与莲心季铵碱对肾性高血压大鼠左室肥厚逆转作用的比较[J].南京中医药大学学报,2008,24(5):327-329.
[26] Xiao J H,Zhang Y L,Feng X L,et al.Effects of isoliensinine on angiotensin II-induced proliferation of porcine coronary arterial smooth muscle cells[J].J Asian Nat Prod Res,2006,8(3):209-216.
[27] 张京梅,李鹏跃,王岚,等.莲子心总生物碱的提取分离及药效学初步研究[J].中国实验方剂学杂志,2009,15(6):26-28.
[28] 王瑞芳,欧来良.莲子心提取物抗心律失常作用及其急性毒性研究[J].中草药,2008,39(3):413-415.
[29] Dong Z X,Zhao X,Gu D F,et al.Comparative effects of liensinine and neferine on the human ether-a-go-go-related gene potassium channel and pharmacological activity analysis[J].Cell PhysiolBiochem,2012,29(3-4):431-442.
[30] 王嘉陵,董登贤,王祖文,等.莲子心中4种生物碱抗心律失常作用的比较[J].中国药学杂志,1992,27(6):359.
[31] 陈默思,贾麟,费宇杰,等.异莲心碱对牵张性心律失常的作用[J].中国医院药学杂志,2006,26(6):658-661.
[32] Wan J,Zhao L,Xu C,et al.Effects of neferine on the pharmacokinetics of amiodarone in rats[J].Biomed Chromatogr,2011,25(8):858-866.
[33] 杨小青,宋金春,谢顺岚,等.莲子心中酚性与非酚性生物碱体外抗氧化活性比较[J].医药导报,2015,34(12):1579-1583.
[34] 杨小青,宋金春,谢顺岚,等.不同提取方法莲子心总生物碱抗氧化活性比较[J].中国医药导报,2015,12(18):100-104.
[35] 胡彩英,曾秋棠.甲基莲心碱对氧化低密度脂蛋白导致平滑肌细胞脂质堆积和增殖的影响[J].华中医学杂志,2006,30(5):401-403.
[36] 王辉,刘月,周本宏,等.甲基莲心碱对高脂血症模型大鼠的作用研究[J].中国药房,2006,17(13):974-976.
[37] 王辉,杨柳,杨俊,等.异莲心碱对大鼠肝匀浆脂质过氧化的影响[J].中国医院药学杂志,2005,25(5):402-404.
[38] Jung H A,Jin S E,Choi R J,et al.Anti-amnesic activity of neferine with antioxidant and anti-inflammatory capacities,as well as inhibition of ChEs and BACE1[J].Life Sci,2010,87(13-14):420-430.
[39] Xie Y,Zhang Y,Zhang L T,et al.Protective effects of alkaloid compounds from Nelumbinis Plumula on tert-butyl hydroperoxide-induced oxidative stress[J].Molecules,2013,18(9):10285-10300.
[40] Liu W,Yi D D,Guo J L,et al.Nuciferine,extracted from Nelumbo nucifera Gaertn,inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer[J].J Ethnopharmacol,2015,165:83-93.
[41] 高天娇,董蕾,史海涛,等.莲子心醇提物抗四氯化碳诱导大鼠肝纤维化的实验研究[J].中国中西医结合杂志,2014,34(12):1476-1480.
[42] Kinnula V L,Fattman C L,Tan R J,et al.Oxidative stress in pulmonary fibrosis:a possible role for redox modulatory therapy[J].Am J Respir Crit Care Med,2005,172(4):417-422.
[43] Xiao J H,Zhang J H,Chen H L,et al.Inhibitory effects of isoliensinine on bleomycin-induced pulmonary fibrosis in mice[J].Planta Med,2005,71(3):225-230.
[44] Zhao L,Wang X,Chang Q,et al.Neferine,a bisbenzylisoquinline alkaloid attenuates bleomycin-induced pulmonary fibrosis[J].Eur J Pharmacol,2010,627(1-3):304-312.
[45] 潘扬,尚文斌,王天山,等.莲子心及Nef对实验性糖尿病及肥胖大鼠模型的影响[J].南京中医药大学学报,2003,19(4):217-219.
[46] 刘双梅,李桂林,汤晓丽,等.甲基莲心碱对2型糖尿病模型大鼠作用的代谢组学研究[J].中国药理学通报,2012,28(4):490-495.
[47] Guan G,Han H,Yang Y,et al.Neferine prevented hyperglycemia-induced endothelial cell apoptosis through suppressing ROS/Akt/NF-κB signal[J].Endocrine,2014,47(3):764-771.
[48] Yang X,Huang M,Yang J,et al.Activity of isoliensinine in improving the symptoms of type 2 diabetic mice via activation of AMP-Activated kinase and regulation of PPARγ[J].J Agric Food Chem,2017,65(33):7168-7178.
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