柴胡及其活性成分防治抑郁症的研究进展

Research progress on Bupleuri Radix and its active components in prevention and treatment of major depressive disorder

摘要

抑郁症(major depressive disorder,MDD)是一种以持续心境低落为主要特征的常见精神障碍,患病率高,已成为导致全球疾病负担的主要原因之一。目前临床治疗MDD以西药为主,但存在不良反应频发、复发率高等问题。中医药凭借多靶点、多通路及不良反应少的优势,在MDD治疗中展现出独特的优势。柴胡(Bupleuri Radix)作为中医疏肝解郁要药,具有疏散退热、疏肝解郁、升举阳气等功效,其在MDD防治中的作用近年来受到广泛关注。本文系统梳理近年来柴胡抗抑郁相关研究,明确柴胡中皂苷类、黄酮类及挥发油类成分为核心抗抑郁活性成分,其作用机制主要涉及调节神经递质平衡、改善下丘脑-垂体-肾上腺轴功能紊乱、保护神经可塑性、抑制神经炎症、调控“微生物-肠-脑轴”及抗氧化应激等。本文从柴胡抗抑郁活性成分、作用机制及复方应用3个方面展开综述,为柴胡及其活性成分的开发利用与临床应用提供参考依据。

Abstract

Major depressive disorder (MDD) is a common psychiatric disorder characterized primarily by persistent low mood. With a high global prevalence, it has become one of the leading causes of the global disease burden. Current clinical treatment for MDD primarily relies on Western medicine, but issues such as frequent adverse reactions and high recurrence rates persist. Traditional Chinese medicine (TCM), leveraging its advantages of multi-target, multi-pathway action and fewer adverse reactions, demonstrates unique potential in MDD treatment. Bupleuri Radix (Chai Hu), a key herb in TCM for soothing the liver and resolving depression, possesses effects such as dispersing heat, soothing the liver and resolving depression, and elevating yang qi. Its role in the prevention and treatment of MDD has garnered significant attention in recent years. This paper systematically reviews recent studies on Bupleuri Radix's antidepressant effects, identifying saponins, flavonoids, and volatile oils as its core active components. Its mechanisms primarily involve regulating neurotransmitter balance, improving hypothalamic-pituitary-adrenal (HPA) axis dysfunction, protecting neural plasticity, suppressing neuroinflammation, modulating the “microbiome-gut-brain axis,” and counteracting oxidative stress. This review covers Bupleuri Radix's active antidepressant components, mechanisms of action, and compound applications, providing a reference for the development, utilization, and clinical application of Bupleuri Radix and its active constituents.

关键词

柴胡 / 抑郁症 / 皂苷类 / 下丘脑-垂体-肾上腺轴 / 神经递质 / 神经炎症反应 / 肠-脑轴

Key words

Bupleuri Radix / major depressive disorder / Saponins / HPA axis / Neurotransmitters / Neuroinflammatory response / Gut-brain axis

[1] CUIJPERS P, SILVERSTEIN M, GLADSTONE T. Preventing depression: challenges and innovations[J]. J Consult Clin Psychol, 2025, 93(4): 191-193.
[2] LIANG WX, GUO HW, LI LY, et al. Ferroptosis: a new target for depression prevention and treatment[J]. J Neural Transm, 2025, 132(7): 979-997.
[3] 张凤, 曾婧, 郑丽, 等. 浅论抑郁症的中医认识[J]. 四川中医, 2025, 43(7): 23-29.
[4] 陈惠芳, 郭萍, 刘鹏宵, 等. 基于Caspase3/Bcl-2/Bax信号通路探究柴胡疏肝散对围绝经期综合征肝郁证大鼠的神经保护作用[J]. 中华中医药杂志, 2025, 40(5): 2544-2550.
[5] 朱文俊, 袁艿君, 唐雅茵, 等. 基于泛素化探讨逍遥散防治抑郁症的潜在机制[J]. 中华中医药杂志, 2025, 40(3): 1316-1319.
[6] TAN L, LI JY, SUN DC, et al. TLR4 as a therapeutic target: Antidepressant mechanism of saikosaponin A in regulating the NF-κB/BDNF axis and mitigating oxidative stress and inflammation in vivo and in vitro[J]. Front Pharmacol, 2025, 16: 1585290.
[7] 陈玟璇, 康舒悦, 赵荻, 等. 从中医辨证分型探讨中药复方防治抑郁症[J]. 中药新药与临床药理, 2025, 36(3): 479-488.
[8] 刘琰, 路洁, 郑昭瀛. 国医大师路志正疏肝化湿联合调情志治疗脾胃病学术思想探析[J]. 世界中西医结合杂志, 2023, 18(5): 907-910.
[9] 苏子昂, 董倩影, 刘泽银, 等. 国医大师邓铁涛治疗冠心病经皮冠状动脉介入术后焦虑抑郁症经验[J]. 中国中医药信息杂志, 2021, 28(12): 103-106.
[10] 周伟康, 郑利钦, 梁天豪, 等. 基于关联规则挖掘国医大师邓铁涛治疗心系病证的用药规律[J]. 辽宁中医杂志, 2021, 48(9): 11-14.
[11] 刘琴, 郭立中. 周仲瑛“疑病多郁”学术思想初探[J]. 环球中医药, 2009, 2(1): 67-68.
[12] 国家药典委员会. 中华人民共和国药典[S]. 2020年. 一部. 北京: 中国医药科技出版社, 2020.
[13] 宋小雪, 闫丽莉, 张文娓, 等. 柴胡化学成分、药理作用研究进展及其质量标志物预测[J]. 中医药信息, 2025, 42(2): 76-81.
[14] 高芳荣, 王威宇, 罗培琰, 等. 基于拟靶向胆汁酸代谢组学筛选柴胡抗抑郁的活性部位[J]. 中草药, 2024, 55(3): 832-841.
[15] 曾德浩, 闫雪. 基于UPLC-MS法研究5种柴胡皂苷在大鼠体内的药代动力学及组织分布[J]. 辽宁中医杂志, 2024, 51(12): 141-146.
[16] 赵一擎, 王艳伟, 杨元, 等. UPLC-MS/MS法同时测定乳核内消液中柴胡皂苷a、柴胡皂苷d、柴胡皂苷b1、柴胡皂苷b2和柴胡皂苷k的含量[J]. 药物分析杂志, 2023, 43(10): 1702-1708.
[17] 胡建燃, 李平, 赵红梅, 等. 柴胡总黄酮的体外抗炎及抗氧化活性研究[J]. 中国食品添加剂, 2023, 34(9): 82-88.
[18] 肖宗雨, 刘艳, 孙延平, 等. 北柴胡地上部分黄酮类化学成分研究[J]. 中药材, 2020, 43(11): 2679-2683.
[19] 邴一凡, 李苏楠, 刘学琴, 等. 基于GC-MS和网络药理学研究南柴胡挥发油抗抑郁作用机制[J]. 特产研究, 2023, 45(1): 32-38.
[20] 刘坤垚, 王奇, 王建新. 不同产地柴胡挥发油成分的测定与比较[J]. 华西药学杂志, 2022, 37(4): 409-413.
[21] 邹宛聪, 张海燕. 基于肠道菌群的植物挥发油药理作用机制研究进展[J]. 中国生物工程杂志, 2024, 44(12): 100-111.
[22] 任历, 邵钰婷, 秦书华, 等. 柴胡皂苷A抗抑郁的靶点识别及作用研究[J]. 天然产物研究与开发, 2024, 36(1): 44-51.
[23] 司玉芳, 刘品, 王平, 等. 基于网络药理学探讨柴胡皂苷a的抗抑郁作用机制[J]. 现代药物与临床, 2025, 40(2): 269-276.
[24] 王君, 薛哲, 刘玥芸, 等. 柴胡皂苷a对肝郁脾虚型抑郁症大鼠海马Notch信号通路的神经保护作用研究[J]. 现代中药研究与实践, 2022, 36(6): 13-17, 28.
[25] 王喜梅, 单艳华, 徐雅芳, 等. 柴胡皂苷D对脑出血大鼠神经保护作用的机制研究[J]. 临床神经病学杂志, 2023, 36(3): 208-215.
[26] 韩雪梅, 朱英, 秦琰杰, 等. 柴胡皂苷D靶向抑制NLRP3炎症小体调控犬尿氨酸代谢的抗抑郁作用机制[J]. 中国医院药学杂志, 2023, 43(14): 1543-1549.
[27] 张云, 高博, 许海军. 柴胡皂苷D基于PI3K/AKT/FoxO1调节神经炎症发挥抗抑郁作用[J]. 实用药物与临床, 2021, 24(5): 395-399.
[28] 刘小军, 刘匡一. HPLC法测定解郁安神颗粒中栀子苷、异阿魏酸、阿魏酸、甘草酸和柴胡皂苷b2[J]. 现代药物与临床, 2025, 40(2): 354-357.
[29] 高兴笑, 郝敏, 李富艳, 等. 基于UPLC-Q-TOF-MS和网络药理学的柴胡醋制前后抗抑郁质量标志物分析[J]. 中国实验方剂学杂志, 2024, 30(3): 124-132.
[30] SONG ZJ, WU YH, LUO LP, et al. Mechanistic insights into the anti-depressant effect of quercetin: an integrated bibliometrics, bioinformatics, and animal experimentation[J]. Front Nutr, 2025, 12: 1612746.
[31] YANG Y, ZHANG YS, CHEN LX, et al. Therapeutic potential of quercetin in depressive symptoms: a systematic review and meta-analysis of preclinical studies[J]. Front Pharmacol, 2025, 16: 1598053.
[32] MOSTARDEIRO VB, ASSMANN CE, SCHIRMANN AA, et al. Quercetin and tranylcypromine improve memory, behavioral performance, and cholinergic function in male rats subjected to chronic restraint stress[J]. Brain Sci, 2025, 15(7): 709.
[33] LEI L, CHEN CY, WANG YF, et al. Efficacy of mangiferin, kaempferol, and diosgenin on models of depression: a systematic review and network meta-analysis of rodent studies[J]. Eur J Pharmacol, 2025, 997: 177555.
[34] SU P, LIU LM, GONG YH, et al. Kaempferol improves depression-like behaviors through shifting microglia polarization and suppressing NLRP3 via tilting the balance of PPARγ and STAT1 signaling[J]. Int Immunopharmacol, 2024, 143(Pt 3): 113538.
[35] 梁玉雕, 谭友果, 张莎, 等. 山奈酚对慢性应激抑郁模型老年大鼠抑郁样行为的影响及机制研究[J]. 中国临床药理学杂志, 2020, 36(24): 4028-4030.
[36] ALQUDAH A, QNAIS E, BSIESO Y, et al. Neuroprotective and antidepressant effects of isorhamnetin: mechanistic evaluations in a reserpine-induced mouse model of pain and depression[J]. Mol Neurobiol, 2025, 62(12): 15798-15812.
[37] XU MJ, HE W, YAN K, et al. Isorhamnetin alleviates inflammation-induced crosstalk between kynurenine pathway and gut microbiota in depressed mice[J]. Biomol Ther, 2025, 33(2): 297-310.
[38] GAMMOH O, QNAIS EY, ATHAMNEH RY, et al. Unraveling the potential of isorhamnetin as an adjuvant in depression treatment with escitalopram[J]. Curr Issues Mol Biol, 2023, 45(9): 7668-7679.
[39] 史慧, 赵新芝. 柴胡通过调节HPA轴和氨基酸类神经递质水平对抑郁模型大鼠的抗抑郁作用[J]. 临床医学研究与实践, 2025, 10(24): 1-4, 50.
[40] WANG XY, SUN ZJ, YANG T, et al. Sodium butyrate facilitates CRHR2 expression to alleviate HPA axis hyperactivity in autism-like rats induced by prenatal lipopolysaccharides through histone deacetylase inhibition[J]. mSystems, 2023, 8(4): e00415-e00423.
[41] 曹珊珊, 石勇, 张瑞华, 等. 抗抑郁柴胡方剂及柴胡皂苷类研究进展[J]. 辽宁中医药大学学报, 2023, 25(9): 197-202.
[42] TIWARI S, PARAMANIK V. Lactobacillus fermentum ATCC 9338 supplementation prevents depressive-like behaviors through glucocorticoid receptor and N-methyl-D-aspartate2b in chronic unpredictable mild stress mouse model[J]. Mol Neurobiol, 2025, 62(6): 7927-7944.
[43] 王重钰, 倪桂莲, 翟晖, 等. 槲皮素对创伤后应激障碍大鼠行为变化和海马IL-6及BDNF表达的影响[J]. 台州学院学报, 2022, 44(6): 64-70.
[44] 熊一凡, 梁小珊, 梁晓涛, 等. 柴胡皂甙a减轻戊四氮诱发的皮质酮抑郁模型小鼠的急性癫痫发作: 基于小胶质细胞介导的炎症反应[J]. 南方医科大学学报, 2024(3): 515-522.
[45] 冯彦. 柴胡石油醚部位与CUMS模型大鼠肠道菌群的相互作用研究[D]. 太原: 山西大学, 2020.
[46] ZHANG AN, GAO SQ, SHEN CH, et al. Bupleuri Radix polysaccharides enhance the efficacy and intestinal absorption of baicalin via regulating intestinal β-glucuronidase activity in MASH mice[J]. Phytomedicine, 2025, 145: 157092.
[47] HUANG MN, YAN Y, DENG ZH, et al. Saikosaponin A and D attenuate skeletal muscle atrophy in chronic kidney disease by reducing oxidative stress through activation of PI3K/AKT/Nrf2 pathway[J]. Phytomedicine, 2023, 114: 154766.
[48] 冯渝梅, 李惠珍, 艾志福, 等. 柴胡防治精神神经疾病的共有物质基础及其生物学机制系统解析[J]. 中草药, 2024, 55(1): 307-319.
[49] 冯丽爽, 李慧, 刘宏伟, 等. 逍遥散加减联合揿针治疗白癜风伴焦虑抑郁临床观察[J]. 陕西中医, 2024, 45(12): 1700-1704.
[50] 李晓君, 王婷, 富文俊, 等. 逍遥散对慢性应激抑郁小鼠海马内糖皮质激素受体磷酸化及脑源性神经营养因子的影响[J]. 中国药学杂志, 2024, 59(24): 2330-2336.
[51] 曹永升, 安红梅, 张金玲, 等. 柴胡疏肝散加减联合舍曲林治疗肝气郁结型老年抑郁症的疗效分析[J]. 中医药学报, 2025, 53(8): 78-82.
[52] 李悦欣, 张芷菁, 郭子伊, 等. 柴胡疏肝散合阿魏酸对CUMS模型大鼠额叶皮层BDNF/TrkB信号通路及单胺类神经递质的调节作用[J]. 中国实验方剂学杂志, 2025, 31(15): 28-37.
[53] 罗磊, 王嘉琳, 宁思思, 等. 针药结合治疗慢性肾脏病2～3b期伴抑郁状态患者的临床观察[J]. 上海中医药杂志, 2022, 56(12): 61-67.
[54] 张扬, 严寒. 柴温桂苓汤对缺血性脑卒中后抑郁痰瘀阻络证下丘脑-垂体-肾上腺素轴功能的影响[J]. 中国医药导刊, 2026, 28(1): 44-50.

基金资助

国家自然科学基金资助项目(82360944);甘肃省中医药科研课题资助项目(GZKZ-2025-34);甘肃省自然科学基金青年科技项目(23JRRA1586);甘肃省药品监督管理局青年科技创新项目(2023GSMPA028);甘肃省中医药研究中心专项开放课题资助项目(zyzx-2025-zx14)