归脾丸(散)与其有效成分抗抑郁作用机制研究进展
Research Progress on Anti-Depression Mechanism of Spleen-Wan Powder and Its Active Components
DOI: 10.12677/TCM.2023.124124, PDF,    科研立项经费支持
作者: 刘雅倩, 李永乐*, 秦铭一, 席亚莉, 李青华：内蒙古医科大学中医学院，内蒙古 呼和浩特；张 锐：内蒙古自治区肿瘤医院，内蒙古 呼和浩特
关键词: 归脾丸(汤)；抑郁；机制；有效成分；Guipi Pill； Depression； Mechanism； Active Ingredient
摘要: 抑郁症是一种严重影响人类工作和生活的精神类疾病，就治疗总费用和生产力损失而言，抑郁症居世界疾病负担首位，严重影响社会和人类健康。近几年的研究表明，中医药在治疗抑郁方面具有一定优势，以归脾丸作为干预抑郁症的经典方剂其抗抑郁作用已被临床反验证，但归脾丸及其有效成分的抗抑郁作用机制尚不清楚，本文通过对以往国内外研究的文献进行系统梳理，发现其主要是从调节下丘脑–垂体–肾上腺(HPA)轴，影响单胺类神经递质分泌，调节脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)的水平，抑制炎症反应，调节肠道菌群的结构，影响氨基酸类神经递质的分泌，影响雌激素的水平等方面发挥抗抑郁作用的。其有效成分主要包括抗炎抗凋亡的黄芪甲苷，以提高BDNF水平为主的酸枣仁皂苷和茯苓多糖，以调节HPA轴为主的远志皂苷，多通路调节的主要包括调节HPA轴，BDNF，单胺神经递质，抗炎抗氧化等途径的人参皂苷、阿魏酸和甘草酸等。
Abstract: Depression is a kind of mental disease that seriously affects people’s work and life. In terms of the total cost of treatment and loss of productivity, depression ranks first in the world’s disease burden, which seriously affects social and human health. Studies in recent years have shown that traditional Chinese medicine has certain advantages in the treatment of depression. The anti- depressant effect of Guipi pill as a classic prescription for depression intervention has been clinically counter-verified, but the mechanism of anti-depressant action of Guipi pill and its effective components is still unclear. This paper systematically reviews the literature of previous domestic and foreign studies. It was found that it plays an antidepressant role in regulating the hypothalamic-pituitary-adrenal axis (HPA), affecting the secretion of monoamine neurotransmitters, regulating the level of brain-derived neurotrophic factor (BDNF), inhibiting inflammatory response, regulating the structure of intestinal flora, affecting the secretion of amino acid neurotransmitters, and affecting the level of estrogen. The active components mainly include astragaloside IV, which is anti-inflammatory and anti-apoptotic, jujube saponins and poria polysaccharide, which mainly improves the level of BDNF, and radix saponins, which mainly regulate the HPA axis. The multi- pathway and multi-point anti-depressants include ginsenosides, ferulic acid and glycyrrhizic acid, which are mainly involved in regulating the HPA axis, BDNF, monoamine neurotransmitter, anti-inflammatory and antioxidant pathways.
文章引用：刘雅倩, 李永乐, 张锐, 秦铭一, 席亚莉, 李青华. 归脾丸(散)与其有效成分抗抑郁作用机制研究进展[J]. 中医学, 2023, 12(4): 806-813. https://doi.org/10.12677/TCM.2023.124124

参考文献

[1] Huang, Y., Wang, Y., Wang, H., et al. (2019) Prevalence of Mental Disorders in China: A Cross-Sectional Epidemiological Study. The Lancet Psychiatry, 6, 211-224. [Google Scholar] [CrossRef] 
[2] 王先萍, 刘丽容, 罗琪丰, 等. 临床常用抗抑郁药物不良反应研究进展[J]. 台州学院学报, 2022, 44(6): 71-77.
[3] 张楚洁, 刘慧萍, 杨璐瑜, 等. 归脾汤有效成分与现代药理学的关联性[J]. 中成药, 2020, 42(6): 1553-1558.
[4] 韦宇婷, 钟静, 钟振国, 等. 归脾丸对小鼠抑郁行为及单胺递质的影响[J]. 西部中医药, 2022, 35(5): 13-17.
[5] 刘立, 徐瑞, 俞晓英. 归脾汤对苯中毒小鼠外周血指标及脑组织中5-TH、DA的影响[J]. 中医研究, 2010, 23(5): 13-16.
[6] Castren, E., Voikar, V. and Rantamaki, T. (2007) Role of Neurotrophic Factors in Depression. Current Opinion in Pharmacology, 7, 18-21. [Google Scholar] [CrossRef] [PubMed]
[7] 李婷婷, 俞晓飞, 李祥婷, 等. 归脾汤对抑郁模型大鼠行为学及海马CA3区BDNF水平的影响[J]. 中华中医药杂志, 2018, 33(7): 2827-2831.
[8] 苏晓云, 贺继平, 崔建梅, 等. 雌二醇对去卵巢大鼠抑郁行为的影响及其可能的作用机制[J]. 解剖学报, 2023, 54(1): 36-41.
[9] 于千, 季颖, 单德红. 归脾汤对抑郁模型大鼠行为学和雌二醇水平的影响[J]. 辽宁中医学院学报, 2006(2): 119-120.
[10] 李春艳, 王宇红, 王华, 等. 抑郁合并失眠对大鼠HPA轴及下丘脑中氨基酸类和单胺类神经递质的影响[J]. 中国药理学通报, 2021, 37(6): 815-822.
[11] 李志强. 归脾汤对抑郁模型大鼠脑内GABA、Glu影响的实验研究[D]: [硕士学位论文]. 哈尔滨: 黑龙江中医药大学, 2013.
[12] 崔艳超, 唐启盛. 归脾汤对产后抑郁模型大鼠HPA轴相关激素及5-羟色胺的影响研究[J]. 北京中医药, 2016, 35(2): 122-126.
[13] 新昕, 季颖. 归脾汤对抑郁模型小鼠血清中IL-4的影响[J]. 实用中医内科杂志, 2011, 25(5): 41-42.
[14] 尚菲. 归脾汤对抑郁模型大鼠IL-1β及IL-1RⅠ型表达的影响[D]: [硕士学位论文]. 沈阳: 辽宁中医药大学, 2009.
[15] Kelly, J.R., et al. (2016) Transferring the Blues: Depression-Associated Gut Microbiota Induces Neurobehavioural Changes in the Rat. Journal of Psychiatric Research, 82, 109-118. [Google Scholar] [CrossRef] [PubMed]
[16] 方正. 通过16SrRNA序列分析探讨抑郁症与肠道菌群之间的相互联系[D]: [硕士学位论文]. 重庆: 重庆医科大学, 2016.
[17] Zheng, P., Zeng, B., Zhou, C., et al. (2016) Gut Microbiome Remodeling Induces Depressive-Like Behaviors through a Pathway Mediated by the Host’s Metabolism. Molecular Psychiatry, 21, 786-796. [Google Scholar] [CrossRef] [PubMed]
[18] 李文佳. 从肠道菌群角度探讨慢性习得性无助模型Balb/c小鼠抑郁伴气虚模型与归脾汤对其进行表型验证[D]: [硕士学位论文]. 南京: 南京中医药大学, 2020.
[19] 朱岳, 黄东梅, 鞠营辉, 等. 基于网络药理学和分子对接技术探讨黄芪甲苷抗抑郁的作用机制[J]. 现代药物与临床, 2022, 37(11): 2465-2474.
[20] Wang, G.L., He, Z.M., Zhu, H.Y., et al. (2017) Involvement of Serotonergic, Noradrenergic and Dopaminergic Systems in the Antidepressant-Like Effect of Ginsenoside Rb1, a Major Active Ingredient of Panax Ginseng C.A. Meyer. Journal of Ethnopharmacology, 204, 118-124. [Google Scholar] [CrossRef] [PubMed]
[21] Wang, G., Lei, C., Tian, Y., et al. (2019) Rb1, the Primary Active Ingredient in Panax ginseng C.A. Meyer, Exerts Antidepressant-Like Effects via the BDNF-Trkb-CREB Pathway. Frontiers in Pharmacology, 10, Article 1034. [Google Scholar] [CrossRef] [PubMed]
[22] Zhang, H., Li, Z., Zhou, Z., et al. (2016) Antidepressant-Like Effects of Ginsenosides: A Comparison of Ginsenoside Rb3 and Its Four Deglycosylated Derivatives, Rg3, Rh2, Compound K, and 20(S)-Protopanaxadiol in Mice Models of Despair. Pharmacology Biochemistry and Behavior, 140, 17-26. [Google Scholar] [CrossRef] [PubMed]
[23] Zhang, Y.Q., Wang, X.B., Xue, R.R., et al. (2019) Ginsenoside Rg1 Attenuates Chronic Unpredictable Mild Stress-inducEd Depressive-Like Effect via Regulating NF-κB/NLRP3 Pathway in Rats. NeuroReport, 30, 893-900. [Google Scholar] [CrossRef] 
[24] 李艳红, 张颖, 黄熙, 等. 基于高效液相色谱技术对冠心Ⅱ号抗抑郁作用物质基础的研究[J]. 新中医, 2021, 53(21): 1-6.
[25] 王文恺, 张蔚, 孙悦, 等. 当归补血汤及其主要活性成分阿魏酸对糖尿病抑郁症模型大鼠的影响及机制研究[J]. 中药新药与临床药理, 2020, 31(6): 649-654.
[26] 胡楚璇, 林壮民, 全佳. 阿魏酸钠对慢性不可预知温和刺激抑郁症大鼠抑郁行为的影响及其机制[J]. 中国医院药学杂志, 2017, 37(17): 1697-1701.
[27] 张璐, 王钱东, 石华孟, 等. 阿魏酸对利血平诱导的疼痛抑郁症的影响[J]. 药学学报, 2013, 48(1): 32-37.
[28] Li, H., Li, J., Zhang, T., et al. (2022) Antidepressant Effect of Jujuboside A on Corticosterone-Induced Depression in Mice. Biochemical and Biophysical Research Communications, 620, 56-62. [Google Scholar] [CrossRef] [PubMed]
[29] 张建英, 汤娟, 张倩, 等. 硫酸茯苓多糖对抑郁症大鼠海马AMPA受体表达的影响[J]. 中国临床心理学杂志, 2019, 27(6): 1086-1091.
[30] 林虓. 制远志中细叶远志皂苷的提取分离及其对雌性小鼠抑郁症的作用研究[D]: [硕士学位论文]. 哈尔滨: 黑龙江中医药大学, 2015.
[31] 刘罡材. HMGB1在母婴分离诱导小鼠抑郁障碍中的作用机制研究[D]: [硕士学位论文]. 成都: 电子科技大学, 2022.
[32] 史碧莹, 刘敏, 于春月, 等. 甘草酸二铵抗抑郁作用机制的研究进展[J]. 现代药物与临床, 2019, 34(5): 1595-1598.