基于中药整合药理学平台的甘味颗粒抗抑郁的分子机制研究
|
摘要
目的探讨甘味颗粒抗抑郁症的分子机制。方法借助中药整合药理学平台(TCMIP),检索甘味颗粒所含的化学成分信息,建立甘味颗粒作用的潜在靶标和疾病靶标之间的相互作用网络;富集计算核心靶标,进行基因功能分析和通路分析,再进一步构建"中药材-化学成分-核心靶标-关键通路"多维关系网络。结果对甘味颗粒预测共得到65个活性成分,涉及33个关键靶标,甘味颗粒通过作用于Rap1信号通路、神经系统、雌激素信号通路、促性腺激素释放激素信号通路、神经胶质瘤、甲状腺激素信号通路、血小板激活、谷氨酸能突触、心肌细胞肾上腺素能信号传导、循环系统等相关生物过程和代谢通路发挥治疗抑郁症的作用。结论初步揭示了甘味颗粒抗抑郁的潜在活性成分及其可能的作用机制。
Objective To explore the molecular mechanism of Ganwei Granules on depressive disorder.Methods Based on the platform of Integrative Pharmacology of Traditional Chinese Medicine(www.tcmip.cn),the chemical composition information in Ganwei Granules were retrieved,an interaction network between potential targets and disease targets of Ganwei Granules was established.Then enrichment calculation of core targets for gene function analysis and pathway analysis was carried out to further construct the multi-dimensional relationship network of "Chinese medicinal materials-chemical composition-core target-key pathway".Results A total of 65 predicted active ingredients of Ganwei Granules interacted with 33 key targets related to depression.The of antidepression mechanism of Ganwei Granules might be associated with Rap1 signaling pathway,nervous system,estrogen signaling pathway,gonadotropin releasing hormone signaling pathway,glioma,thyroid hormone signaling pathway,platelet activation,glutamatergic synapse,adrenergic signal transduction in cardiac myocytes,circulatory system and other pathways.Conclusion This research may reveal the potential active ingredients of Ganwei Granules in treatment of depression and its possible mechanism.
Objective To explore the molecular mechanism of Ganwei Granules on depressive disorder.Methods Based on the platform of Integrative Pharmacology of Traditional Chinese Medicine(www.tcmip.cn),the chemical composition information in Ganwei Granules were retrieved,an interaction network between potential targets and disease targets of Ganwei Granules was established.Then enrichment calculation of core targets for gene function analysis and pathway analysis was carried out to further construct the multi-dimensional relationship network of "Chinese medicinal materials-chemical composition-core target-key pathway".Results A total of 65 predicted active ingredients of Ganwei Granules interacted with 33 key targets related to depression.The of antidepression mechanism of Ganwei Granules might be associated with Rap1 signaling pathway,nervous system,estrogen signaling pathway,gonadotropin releasing hormone signaling pathway,glioma,thyroid hormone signaling pathway,platelet activation,glutamatergic synapse,adrenergic signal transduction in cardiac myocytes,circulatory system and other pathways.Conclusion This research may reveal the potential active ingredients of Ganwei Granules in treatment of depression and its possible mechanism.
引文
[1]Leubner D,Hinterberger T.Reviewing the effectiveness of music interventions in treating depression[J].Front Psychol,2017,8:1109.
[2]Dennis C L,Dowswell T.Interventions(other than pharmacological,psychosocial or psychological)for treating antenatal depression[J].Cochrane Database Syst Rev,2013,(7):CD006795.
[3]刘佳莉,苑玉和,陈乃宏.抑郁症的治疗研究进展[J].中国药理学通报,2011,27(9):1193-1196.
[4]隋璐,王晓红.抑郁症"从肝论治"现代研究进展[J].辽宁中医药大学学报,2018,20(2):168-170.
[5]许乐思,陈雨,王梦莎,等.抑郁症的中医临床辨证规律研究[J].湖北中医药大学学报,2017,19(3):37-40.
[6]薛晓娜,李慧峰,荆然,等.甘味颗粒对小鼠急性应激诱导行为绝望抑郁的改善作用及其机制研究[J].现代药物与临床,2016,31(1):17-20.
[7]许海玉,杨洪军.整合药理学:中药现代研究新模式[J].中国中药杂志,2014,39(3):357-362.
[8]王萍,唐仕欢,苏瑾,等.基于整合药理学的中药现代研究进展[J].中国中药杂志,2018,43(7):1297-1302.
[9]戈宏焱,陈博,许丹,等.柴胡皂苷A对抑郁模型大鼠脑中单胺类神经递质及其代谢产物含量的影响[J].高等学校化学学报,2008,29(8):1535-1538.
[10]杨久山,张楠,宋铭晶,等.柴胡总皂苷对小鼠抑郁样行为及学习记忆障碍的改善作用[J].中国实验方剂学杂志,2016,22(24):134-139.
[11]李琴.甘松新酮抗抑郁作用及作用机制初探[D].北京:北京中医药大学,2011.
[12]谢纲,袁莉,唐正平,等.五味子提取物的抗抑郁作用研究[J].湖南中医杂志,2010,26(5):123-124.
[13]许方敏,薛瑞,叶洪涛,等.五味子醇甲对小鼠抑郁样行为的影响[J].中国药理学与毒理学杂志,2017,31(3):244-249.
[14]樊紫周,赵伟鸿,果嘉,等.甘草黄酮的抗抑郁作用及对海马脑区神经再生的保护作用[J].药学学报,2012(12):1612-1617.
[15]Delgado P L.Depression:the case for a monoamine deficiency[J].J Clin Psychiatry,2000,61(Suppl 6):7-11.
[16]Ding Y Q,Kaneko T,Nomura S,et al.Immunohistochemical localization of mu-opioid receptors in the central nervous system of the rat[J].J Comp Neurol,1996,367(3):375-402.
[17]Richards E M,Mathews D C,Luckenbaugh D A,et al.A randomized,placebo-controlled pilot trial of the delta opioid receptor agonist AZD2327 in anxious depression[J].Psychopharmacology(Berl),2016,233(6):1119-1130.
[18]Torregrossa M M,Isgor C,Folk J E,et al.The deltaopioid receptor agonist(+)BW373U86regulates BDNF mRNA expression in rats[J].Neuropsychopharmacology,2004,29(4):649-659.
[19]Basheer R,Strecker R E,Thakkar M M,et al.Adenosine and sleep-wake regulation[J].Prog Neurobiol,2004,73(6):379-396.
[20]Fredholm B B,IJzerman A P,Jacobson K A,et al.International Union of Pharmacology.XXV.Nomenclature and classification of adenosine receptors[J].Pharmacol Rev,2001,53(4):527-552.
[21]李玲,万礼霞.抑郁症中腺苷对ERK1/2影响的研究进展[J].中国医疗前沿,2010,5(21):21-23.
[22]Hill S J,Ganellin C R,Timmerman H,et al.International Union of Pharmacology.XIII.Classification of histamine receptors[J].Pharmacol Rev,1997,49(3):253-278.
[23]Brown R E,Stevens D R,Haas H L.The physiology of brain histamine[J].Prog Neurobiol,2001,63(6):637-672
[24]Haas H,Panula P.The role of histamine and the tuberomamillary nucleus in the nervous system[J].Nat Rev Neurosci,2003,4(2):121-130.
[25]Millan M J.Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states:focus on novel therapeutic strategies[J].Therapie,2005,60(5):441-460.
[26]李苒,高杉,李琳,等.抑郁症发病机制的研究进展[J].天津中医药,2013,30(2):121-125.
[27]裴妙荣,李慧峰.一种抗抑郁药物组合物[P].中国:CN104435298A,2015-03-25.
[2]Dennis C L,Dowswell T.Interventions(other than pharmacological,psychosocial or psychological)for treating antenatal depression[J].Cochrane Database Syst Rev,2013,(7):CD006795.
[3]刘佳莉,苑玉和,陈乃宏.抑郁症的治疗研究进展[J].中国药理学通报,2011,27(9):1193-1196.
[4]隋璐,王晓红.抑郁症"从肝论治"现代研究进展[J].辽宁中医药大学学报,2018,20(2):168-170.
[5]许乐思,陈雨,王梦莎,等.抑郁症的中医临床辨证规律研究[J].湖北中医药大学学报,2017,19(3):37-40.
[6]薛晓娜,李慧峰,荆然,等.甘味颗粒对小鼠急性应激诱导行为绝望抑郁的改善作用及其机制研究[J].现代药物与临床,2016,31(1):17-20.
[7]许海玉,杨洪军.整合药理学:中药现代研究新模式[J].中国中药杂志,2014,39(3):357-362.
[8]王萍,唐仕欢,苏瑾,等.基于整合药理学的中药现代研究进展[J].中国中药杂志,2018,43(7):1297-1302.
[9]戈宏焱,陈博,许丹,等.柴胡皂苷A对抑郁模型大鼠脑中单胺类神经递质及其代谢产物含量的影响[J].高等学校化学学报,2008,29(8):1535-1538.
[10]杨久山,张楠,宋铭晶,等.柴胡总皂苷对小鼠抑郁样行为及学习记忆障碍的改善作用[J].中国实验方剂学杂志,2016,22(24):134-139.
[11]李琴.甘松新酮抗抑郁作用及作用机制初探[D].北京:北京中医药大学,2011.
[12]谢纲,袁莉,唐正平,等.五味子提取物的抗抑郁作用研究[J].湖南中医杂志,2010,26(5):123-124.
[13]许方敏,薛瑞,叶洪涛,等.五味子醇甲对小鼠抑郁样行为的影响[J].中国药理学与毒理学杂志,2017,31(3):244-249.
[14]樊紫周,赵伟鸿,果嘉,等.甘草黄酮的抗抑郁作用及对海马脑区神经再生的保护作用[J].药学学报,2012(12):1612-1617.
[15]Delgado P L.Depression:the case for a monoamine deficiency[J].J Clin Psychiatry,2000,61(Suppl 6):7-11.
[16]Ding Y Q,Kaneko T,Nomura S,et al.Immunohistochemical localization of mu-opioid receptors in the central nervous system of the rat[J].J Comp Neurol,1996,367(3):375-402.
[17]Richards E M,Mathews D C,Luckenbaugh D A,et al.A randomized,placebo-controlled pilot trial of the delta opioid receptor agonist AZD2327 in anxious depression[J].Psychopharmacology(Berl),2016,233(6):1119-1130.
[18]Torregrossa M M,Isgor C,Folk J E,et al.The deltaopioid receptor agonist(+)BW373U86regulates BDNF mRNA expression in rats[J].Neuropsychopharmacology,2004,29(4):649-659.
[19]Basheer R,Strecker R E,Thakkar M M,et al.Adenosine and sleep-wake regulation[J].Prog Neurobiol,2004,73(6):379-396.
[20]Fredholm B B,IJzerman A P,Jacobson K A,et al.International Union of Pharmacology.XXV.Nomenclature and classification of adenosine receptors[J].Pharmacol Rev,2001,53(4):527-552.
[21]李玲,万礼霞.抑郁症中腺苷对ERK1/2影响的研究进展[J].中国医疗前沿,2010,5(21):21-23.
[22]Hill S J,Ganellin C R,Timmerman H,et al.International Union of Pharmacology.XIII.Classification of histamine receptors[J].Pharmacol Rev,1997,49(3):253-278.
[23]Brown R E,Stevens D R,Haas H L.The physiology of brain histamine[J].Prog Neurobiol,2001,63(6):637-672
[24]Haas H,Panula P.The role of histamine and the tuberomamillary nucleus in the nervous system[J].Nat Rev Neurosci,2003,4(2):121-130.
[25]Millan M J.Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states:focus on novel therapeutic strategies[J].Therapie,2005,60(5):441-460.
[26]李苒,高杉,李琳,等.抑郁症发病机制的研究进展[J].天津中医药,2013,30(2):121-125.
[27]裴妙荣,李慧峰.一种抗抑郁药物组合物[P].中国:CN104435298A,2015-03-25.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |