红参皂苷组分对大鼠血浆中神经化学物质的影响
|
摘要
目的考察红参皂苷组分A和B对大鼠血浆中15种神经化学物质水平的影响。方法将红参总皂苷经大孔吸附树脂分离纯化制备得到皂苷组分A和B,采用高效液相色谱-质谱法(UPLC-Q-TOF-MS/MS)测定其中皂苷成分的组成和量,并采用超高效液相色谱-三重四级杆质谱(UPLC-QQQ-MS/MS)测定大鼠血浆中多巴胺(DA)、肾上腺素(E)、去甲肾上腺素(NE)、5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、酪氨酸(Tyr)、甘氨酸(Gly)、谷氨酸(Glu)、谷氨酰胺(Gln)、天冬氨酸(Asp)、牛磺酸(Tau)、丝氨酸(Ser)、色氨酸(Try)、乙酰胆碱(Ach)、组胺(His)共15种神经化学物质的量及其变化情况。结果通过对皂苷组成和量与神经化学物质之间的内在联系分析,发现组分A和B在皂苷成分组成方面存在明显差异,极性较大皂苷类成分主要集中在组分A中,而组分B中含有的皂苷成分极性相对较小。组分A各剂量组的大鼠血浆中Ach、Tau、Glu、Gln、Asp、Tyr、E、NE、DA的量升高,组分B各剂量组的大鼠血浆中Gly、His、5-HT、Ser、5-HIAA、Try的量显著升高,并且与给药剂量呈正相关趋势,提示极性较大皂苷组分可提高兴奋性神经化学物质的量,而极性较小皂苷组分表现为提高抑制性神经化学物质的量。结论红参皂苷对中枢神经化学物质的量具有调节作用,极性较小的皂苷组分与保持大脑活动、改善记忆功能、防止脑部疲劳、维持觉醒状态和神经系统抗衰老等作用相关性较大,而极性较大的皂苷组分与调节精神节律、削弱应激反应和改善睡眠等作用相关性较大。
Objective To investigate the effects of red ginseng saponin components A and B on 15 neurochemicals in rat plasma. Methods Saponin components A and B were prepared from red ginseng total saponin by macroporous adsorption resin. The composition and contents of saponin components A and B were detected using UPLC-Q-TOF-MS/MS method. A total of 15 kinds of neurochemical substances such as dopamine(DA), adrenaline(E), norepinephrine(NE), serotonin(5-HT), 5-hydroxytryptamine(5-hydroxytryptamine), tyrosine(Tyr), glycine(Gly), glutamic acid(Glu), glutamine(Gln), aspartic acid(Asp), taurine(Tau), serine(Ser), tryptophan(Try), acetylcholine(Ach), and histamine(His) were measured by high performance liquid chromatography-mass spectrometry(UPLC-QQQ-MS/MS). Results By analyzing the intrinsic relationship between saponin composition and amount of neurochemicals, it was found that components A and B had significant differences in saponin composition, and the larger polar saponins were mainly concentrated in component A. The polar of saponin contained in B is relatively small. The levels of Ach, Tau, Glu, Gln, Asp, Tyr, E, NE, and DA in rat plasma of each dose group were increased, and the plasma levels of Gly, His, 5-HT, Ser, HIAA, and Try were significantly increased and positively correlated with the dose, suggesting that the larger polar saponins could increase the excitatory neurochemical content and the smaller saponin fraction inhibitory neurochemicals. Conclusion Red ginseng has a moderating effect on the content of central nervous system. The content of smaller polar saponins is related to the maintenance of brain activity, improvement of memory function, prevention of brain fatigue, maintenance of awakening and nervous system of anti-aging, while the larger polar saponin fraction is associated with the regulation of psychiatric rhythm, reduction of stress response and improvement of sleeping.
Objective To investigate the effects of red ginseng saponin components A and B on 15 neurochemicals in rat plasma. Methods Saponin components A and B were prepared from red ginseng total saponin by macroporous adsorption resin. The composition and contents of saponin components A and B were detected using UPLC-Q-TOF-MS/MS method. A total of 15 kinds of neurochemical substances such as dopamine(DA), adrenaline(E), norepinephrine(NE), serotonin(5-HT), 5-hydroxytryptamine(5-hydroxytryptamine), tyrosine(Tyr), glycine(Gly), glutamic acid(Glu), glutamine(Gln), aspartic acid(Asp), taurine(Tau), serine(Ser), tryptophan(Try), acetylcholine(Ach), and histamine(His) were measured by high performance liquid chromatography-mass spectrometry(UPLC-QQQ-MS/MS). Results By analyzing the intrinsic relationship between saponin composition and amount of neurochemicals, it was found that components A and B had significant differences in saponin composition, and the larger polar saponins were mainly concentrated in component A. The polar of saponin contained in B is relatively small. The levels of Ach, Tau, Glu, Gln, Asp, Tyr, E, NE, and DA in rat plasma of each dose group were increased, and the plasma levels of Gly, His, 5-HT, Ser, HIAA, and Try were significantly increased and positively correlated with the dose, suggesting that the larger polar saponins could increase the excitatory neurochemical content and the smaller saponin fraction inhibitory neurochemicals. Conclusion Red ginseng has a moderating effect on the content of central nervous system. The content of smaller polar saponins is related to the maintenance of brain activity, improvement of memory function, prevention of brain fatigue, maintenance of awakening and nervous system of anti-aging, while the larger polar saponin fraction is associated with the regulation of psychiatric rhythm, reduction of stress response and improvement of sleeping.
引文
[1]中国药典[S].一部.2015.
[2]李慧,刘淑莹,王冰.人参皂苷对HPA轴作用的研究进展[J].药学学报,2014,49(5):569-575.
[3]Voces J,Alvarez A I,Vila L,et al.Effects of administration of the standardized Panax ginseng extract G115 on hepanic antioxidant function after exhaustive exercise[J].Comp Biochem Physiol,1999,123(2):175-184.
[4]雷秀娟,冯凯,孙立伟.人参皂苷抗衰老机制的研究进展[J].氨基酸与生物资源,2010,32(1):44-47.
[5]许海顺,蒋剑平,徐攀,等.红参多糖抗氧化活性的研究[J].浙江中医药大学学报,2011,35(6):909-912.
[6]张酉珍,苏光悦,夏晓艳,等.天然达玛烷型皂苷降血糖作用的研究进展[J].中草药,2016,47(15):2758-2763.
[7]赵琛,苏光悦,赵余庆.人参皂苷及其衍生物抗结肠癌作用及机制的研究进展[J].中草药,2015,46(16):2477-2483.
[8]程慧,宋新波,张丽娟.人参皂苷Rg3与Rh2的研究进展[J].药物评价研究,2010,33(4):307-311.
[9]Odashima S,Ota T,Kohno H,et al.Control of phenotypic expression of cultured B16 melanoma cells by plant glycosides[J].Cancer Res,1985,45(6):2781-2784.
[10]Yamaguchi Y,Haruta K,Kobayashi H.Effects of ginsenosides on impaired performance induced in the rat by scopolamine in a radial-arm maze[J].Psychoneuroendocrinology,1995,20(6):645-653.
[11]Yamaguchi Y,Higashi M,Kobayashi H.Effect of oral and intraventricular administration of ginsenoside Rg1 on the performance impaired by scopolamine in rats[J].Biomedical Res,1996,17(6):487-490.
[12]Kimura T,Saunders P A,Kim H S,et al.Interaction of ginsenosides with ligand-blindings of GABA and GABA receptors[J].Gen Pharmacol,1994,25(1):193-199.
[13]Yuan C S,Attele A S,Wu J A,et al.Modulation of American ginseng on brainstem GABA ergic effects in the rat[J].Ethnopharmacol,1998,62(3):215-222.
[14]王雅丽,黄俊山.神经递质与睡眠觉醒及学习记忆的关系研究[J].医学综述,2011,17(1):15-18.
[15]Brichta L,Greengard P,Flajolet M.Advances in the pharmacological treatment of Parkinson’s disease:Targeting neurotransmitter systems[J].Trends Neurosci,2013,36(9):543-554.
[16]Carlsson A,Waters N,Carlsson M L.Neurotransmitter interactions in schizophrenia-therapeutic implications[J].Eur Arch Psychiatry Clin Neurosci,1999,249(Suppl 4):37-43.
[17]Kenche V B,Zawisza I,Masters C L,et al.Mixed ligand Cu2+complexes of a model therapeutic with Alzheimer’s amyloid-βpeptide and monoamine neurotransmitters[J].Inorg Chem,2013,52(8):4303-4318.
[18]Zhao L S,Zheng S N,Su G Y,et al.In vivo study on the neurotransmitters and their metabolites change in depressive disorder rat plasma by ultra high performance liquid chromatography coupled to tandem mass spectrometry[J].J Chromatogr B,2015(988):59-65.
[19]杨培,李雪春,田晶辰,等.格优泰对抑郁大鼠脑内氨基酸水平的影响[J].世界科学技术—中医药现代化,2014,16(10):2174-217.
[20]赵瑜,陈波,罗旭彪,等.大孔吸附树脂分离纯化人参二醇类和三醇类皂甙[J].天然产物研究与开发,2004,16(3):235-238.
[21]Wu W,Sun L,Zhang Z,et al.Profiling and multivariate statistical analysis of Panax ginseng based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry[J].J Pharm Biomed Anal,2015,107:141-150.
[22]黄鑫,李帅坪,张勇,等.UPLC-MS/MS法测定大鼠海马和大脑皮层中生物胺类及氨基酸类神经化学物质[J].分析化学,2016,44(11):1652-1658.
[23]皮子凤,王倩倩,张静,等.北五味子对糖尿病脑病大鼠脑中神经活性物质含量影响的在线微透析-高效液相色谱-串联质谱联用分析[J].高等学校化学学报,2015,36(3):442-448.
[24]G?tz J,Schild A,Hoerndli F,et al.Amyloid-induced neurofibrillary tangle formation in Alzheimer’s disease:insight from transgenic mouse and tissue-culture models[J].Intl J Dev Neurosci,2004,22(7):453-465.
[25]耿磊,刘德山,郝媛媛,等.脑神康对糖尿病大鼠脑内单胺类神经递质含量的影响[J].山东大学学报,2008,46(7):689-692.
[26]Perez-Garcia G,Meneses A.Memory time-course:m RNA5-HT1A and 5-HT7 receptors[J].Behav Brain Res,2009,202(1):102-113.
[27]Sarkisyan G,Hedlund P B.The 5-HT7 receptor is involved in allocentric spatial memory information processing[J].Behav Brain Res,2009,202(1):26-31.
[28]何文娟,阮怀珍.D-丝氨酸在神经元-胶质细胞间通讯的新进展[J].生理科学进展,2009,40(4):303-307.
[29]刘天雅,洪宗元,曲卫敏,等.中枢组胺能神经系统调节睡眠-觉醒机制研究进展[J].药学学报,2011,46(3):247-252.
[2]李慧,刘淑莹,王冰.人参皂苷对HPA轴作用的研究进展[J].药学学报,2014,49(5):569-575.
[3]Voces J,Alvarez A I,Vila L,et al.Effects of administration of the standardized Panax ginseng extract G115 on hepanic antioxidant function after exhaustive exercise[J].Comp Biochem Physiol,1999,123(2):175-184.
[4]雷秀娟,冯凯,孙立伟.人参皂苷抗衰老机制的研究进展[J].氨基酸与生物资源,2010,32(1):44-47.
[5]许海顺,蒋剑平,徐攀,等.红参多糖抗氧化活性的研究[J].浙江中医药大学学报,2011,35(6):909-912.
[6]张酉珍,苏光悦,夏晓艳,等.天然达玛烷型皂苷降血糖作用的研究进展[J].中草药,2016,47(15):2758-2763.
[7]赵琛,苏光悦,赵余庆.人参皂苷及其衍生物抗结肠癌作用及机制的研究进展[J].中草药,2015,46(16):2477-2483.
[8]程慧,宋新波,张丽娟.人参皂苷Rg3与Rh2的研究进展[J].药物评价研究,2010,33(4):307-311.
[9]Odashima S,Ota T,Kohno H,et al.Control of phenotypic expression of cultured B16 melanoma cells by plant glycosides[J].Cancer Res,1985,45(6):2781-2784.
[10]Yamaguchi Y,Haruta K,Kobayashi H.Effects of ginsenosides on impaired performance induced in the rat by scopolamine in a radial-arm maze[J].Psychoneuroendocrinology,1995,20(6):645-653.
[11]Yamaguchi Y,Higashi M,Kobayashi H.Effect of oral and intraventricular administration of ginsenoside Rg1 on the performance impaired by scopolamine in rats[J].Biomedical Res,1996,17(6):487-490.
[12]Kimura T,Saunders P A,Kim H S,et al.Interaction of ginsenosides with ligand-blindings of GABA and GABA receptors[J].Gen Pharmacol,1994,25(1):193-199.
[13]Yuan C S,Attele A S,Wu J A,et al.Modulation of American ginseng on brainstem GABA ergic effects in the rat[J].Ethnopharmacol,1998,62(3):215-222.
[14]王雅丽,黄俊山.神经递质与睡眠觉醒及学习记忆的关系研究[J].医学综述,2011,17(1):15-18.
[15]Brichta L,Greengard P,Flajolet M.Advances in the pharmacological treatment of Parkinson’s disease:Targeting neurotransmitter systems[J].Trends Neurosci,2013,36(9):543-554.
[16]Carlsson A,Waters N,Carlsson M L.Neurotransmitter interactions in schizophrenia-therapeutic implications[J].Eur Arch Psychiatry Clin Neurosci,1999,249(Suppl 4):37-43.
[17]Kenche V B,Zawisza I,Masters C L,et al.Mixed ligand Cu2+complexes of a model therapeutic with Alzheimer’s amyloid-βpeptide and monoamine neurotransmitters[J].Inorg Chem,2013,52(8):4303-4318.
[18]Zhao L S,Zheng S N,Su G Y,et al.In vivo study on the neurotransmitters and their metabolites change in depressive disorder rat plasma by ultra high performance liquid chromatography coupled to tandem mass spectrometry[J].J Chromatogr B,2015(988):59-65.
[19]杨培,李雪春,田晶辰,等.格优泰对抑郁大鼠脑内氨基酸水平的影响[J].世界科学技术—中医药现代化,2014,16(10):2174-217.
[20]赵瑜,陈波,罗旭彪,等.大孔吸附树脂分离纯化人参二醇类和三醇类皂甙[J].天然产物研究与开发,2004,16(3):235-238.
[21]Wu W,Sun L,Zhang Z,et al.Profiling and multivariate statistical analysis of Panax ginseng based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry[J].J Pharm Biomed Anal,2015,107:141-150.
[22]黄鑫,李帅坪,张勇,等.UPLC-MS/MS法测定大鼠海马和大脑皮层中生物胺类及氨基酸类神经化学物质[J].分析化学,2016,44(11):1652-1658.
[23]皮子凤,王倩倩,张静,等.北五味子对糖尿病脑病大鼠脑中神经活性物质含量影响的在线微透析-高效液相色谱-串联质谱联用分析[J].高等学校化学学报,2015,36(3):442-448.
[24]G?tz J,Schild A,Hoerndli F,et al.Amyloid-induced neurofibrillary tangle formation in Alzheimer’s disease:insight from transgenic mouse and tissue-culture models[J].Intl J Dev Neurosci,2004,22(7):453-465.
[25]耿磊,刘德山,郝媛媛,等.脑神康对糖尿病大鼠脑内单胺类神经递质含量的影响[J].山东大学学报,2008,46(7):689-692.
[26]Perez-Garcia G,Meneses A.Memory time-course:m RNA5-HT1A and 5-HT7 receptors[J].Behav Brain Res,2009,202(1):102-113.
[27]Sarkisyan G,Hedlund P B.The 5-HT7 receptor is involved in allocentric spatial memory information processing[J].Behav Brain Res,2009,202(1):26-31.
[28]何文娟,阮怀珍.D-丝氨酸在神经元-胶质细胞间通讯的新进展[J].生理科学进展,2009,40(4):303-307.
[29]刘天雅,洪宗元,曲卫敏,等.中枢组胺能神经系统调节睡眠-觉醒机制研究进展[J].药学学报,2011,46(3):247-252.