1.成都中医药大学,四川省成都市金牛区十二桥路37号,610075
2.成都中医药大学附属医院
收稿:2022-03-29,
修回:2022-07-26,
纸质出版:2023-06-02
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张勇,刘美君,李锐锋等.中医药干预TLR4/NLRP3信号通路治疗抑郁症的研究概况[J].中医杂志,2023,64(11):1179-1184.
ZHANG Yong,LIU Meijun,LI Ruifeng,et al.Overview of Research in Traditional Chinese Medicine for the Treatment of Depression by Intervention on TLR4/NLRP3 Signaling Pathway[J].Journal of Traditional Chinese Medicine,2023,64(11):1179-1184.
张勇,刘美君,李锐锋等.中医药干预TLR4/NLRP3信号通路治疗抑郁症的研究概况[J].中医杂志,2023,64(11):1179-1184. DOI: 10.13288/j.11-2166/r.2023.11.018.
ZHANG Yong,LIU Meijun,LI Ruifeng,et al.Overview of Research in Traditional Chinese Medicine for the Treatment of Depression by Intervention on TLR4/NLRP3 Signaling Pathway[J].Journal of Traditional Chinese Medicine,2023,64(11):1179-1184. DOI: 10.13288/j.11-2166/r.2023.11.018.
应激诱导的免疫/炎症反应是抑郁症发生发展的关键病理机制,模式识别受体Toll样受体4(TLR4)/NOD样受体蛋白3(NLRP3)信号通路介导的免疫/炎症反应与抑郁症的形成和发展密切相关。中医药有关该通路抗抑郁的机制研究近年来成为关注点之一,中药复方如逍遥散、柴胡疏肝散、小建中汤等,中药药对如柴胡-白芍、桂枝-白芍、栀子-川芎等,中药单体如红花提取物、去氧五味子素、银杏酮酯、麝香酮、女贞子酚苷等可能通过抑制TLR4/NLRP3信号通路,下调TLR4、NLRP3、髓样分化因子88(MyD88)、核转录因子κB(NF-κB)、信号转接凋亡相关斑点样蛋白(ASC)等关键蛋白表达及白细胞介素1β(IL-1β)、白细胞介素18(IL-18)、肿瘤坏死因子α(TNF-α)等炎症因子水平,调控应激诱导的免疫/炎症反应,发挥抗抑郁作用。建议今后采用多种现代检测技术,从不同维度、不同层次,进一步探索中医药在TLR4/NLRP3信号通路中的抗抑郁机制,为中医药治疗抑郁症提供更多科学有力的证据。
The immune/inflammatory response induced by stress is a key pathological mechanism for the occurrence and development of depression. The immune/inflammatory response mediated by the Toll-like receptor 4 (TLR4)/NOD like receptor protein 3 (NLRP3) signaling pathway is closely related to the formation and development of depression. In recent years, researches on the antidepressant mechanism of the TLR4/NLRPS pathway in traditional Chinese medicine (TCM) has become a hot topic. TCM compound formulas such as
Xiaoyao Powder
(逍遥散),
Chaihu Shugan Powder
(柴胡疏肝散), and
Xiaojianzhong Decoction
(小建中汤), herbal pairs such as Chaihu (
Radix Bupleuri
) - Baishao (
Radix Paeoniae Alba
), Guizhi (
Ramulus Cinnamomi
) -Baishao (
Radix Paeoniae Alba
), and Zhizi (
Fructus Gardeniae
) - Chuanxiong (
Rhizoma Chuanxiong
), and monomers such as extract of Honghua (
Flos Carthami
), deoxyschizandrin, ginkgo ketone ester, muscone, and citrus glycosides, may be possible to inhibit the TLR4/NLRP3 signaling pathway and down-regulate the expression of key proteins such as TLR4, NLRP3, myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB), and signal transduction apoptosis-associated speck-like protein (ASC), as well as the levels of inflammatory factors such as interleukin 1β (IL-1β), interleukin 18 (IL-18), and tumor necrosis factor α (TNF-α), thereby regulating stress-induced immune/inflammatory responses and exert antidepressant effects. It is suggested that various modern detection techniques be used in the future to further explore the antidepressant mechanism of TLR4/NLRP3 signaling pathway from different dimensions and levels, so as to provide more scientific and powerful evidence for the treatment of depression with TCM.
唐启盛 . 抑郁障碍中西医研究进展述评 [J]. 北京中医药大学学报 , 2022 , 45 ( 9 ): 871 - 877 .
谷春华 , 任君霞 , 杨立波 , 等 . 解郁除烦胶囊治疗抑郁症334例多中心随机双盲对照试验 [J]. 中医杂志 , 2016 , 57 ( 15 ): 1297 - 1302 .
李莉 . 中药解郁丸合并帕罗西汀对抑郁症增效治疗的对照观察 [J]. 中国药物与临床 , 2012 , 12 ( 10 ): 1331 - 1332 .
LEONARD BE . Inflammation and depression: a causal or coincidental link to the pathophysiology? [J]. Acta Neuropsychiatr , 2018 , 30 ( 1 ): 1 - 16 .
FLESHNER M , FRANK M , MAIER SF . Danger signals and inflammasomes: stress-evoked sterile inflammation in mood disorders [J]. Neuropsychopharmacology , 2017 , 42 ( 1 ): 36 - 45 .
姜会梨 . 针刺对CRS大鼠海马TLR4信号通路/NLRP3炎性小体诱导免疫/炎性激活的抗炎效应机制 [D]. 北京 : 北京中医药大学 , 2018 .
FELGER JC , LOTRICH FE . Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications [J]. Neuroscience , 2013 , 246 : 199 - 229 . doi: 10.1016/j.neuroscience.2013.04.060 http://dx.doi.org/10.1016/j.neuroscience.2013.04.060 .
张娟 , 尚德静 . Toll样受体4(TLR4)信号通路及其靶向药物的研究进展 [J]. 细胞与分子免疫学杂志 , 2021 , 37 ( 7 ): 657 - 662 .
FIGUEROA-HALL LK , PAULUS MP , SAVITZ J . Toll-Like receptor signaling in depression [J]. Psychoneuroendocrinology , 2020 , 121 : 104843 . doi: 10.1016/j.psyneuen. 2020.104843 http://dx.doi.org/10.1016/j.psyneuen.2020.104843 .
GAZAL M , SOUZA LD , FUCOLO BA , et al . The impact of cognitive behavioral therapy on IL-6 levels in unmedicated women experiencing the first episode of depression: a pilot study [J]. Psychiatry Res , 2013 , 209 ( 3 ): 742 - 745 .
LIU SP , LI XY , LI Z , et al . Octanoylated Ghrelin inhi-bits the activation of the palmitic acid-induced TLR4/NF-κB signaling pathway in THP-1 macrophages [J]. ISRN Endocrinol , 2012 , 2012 : 237613 . doi: 10.5402/2012/237613 http://dx.doi.org/10.5402/2012/237613 .
曾九僧 , 纪雅菲 , 方洋 , 等 . NLRP3炎症小体在抑郁症中的作用及中药干预研究进展 [J]. 中草药 , 2021 , 52 ( 11 ): 3418 - 3428 .
PACE TW , HU F , MILLER AH . Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression [J]. Brain Behav Immun , 2007 , 21 ( 1 ): 9 - 19 .
KAUFMANN FN , COSTA AP , GHISLENI G , et al . NLRP3 inflammasome-driven pathways in depression: clinical and preclinical findings [J]. Brain Behav Immun , 2017 , 64 : 367 - 383 . doi: 10.1016/j.bbi.2017.03.002 http://dx.doi.org/10.1016/j.bbi.2017.03.002 .
STERTZ L , FRIES GR , ROSA AR , et al . Damage-associated molecular patterns and immune activation in bipolar disorder [J]. Acta Psychiatr Scand , 2015 , 132 ( 3 ): 211 - 217 .
MAES M , GALECKI P , CHANG YS , et al . A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness [J]. Prog Neuropsychopharmacol Biol Psychiatry , 2011 , 35 ( 3 ): 676 - 692 .
WANG M , YAN S , ZHOU Y , et al . Trans-Cinnamaldehyde reverses depressive-like behaviors in chronic unpredictable mild stress rats by inhibiting NF-κB/NLRP3 inflammasome pathway [J]. Evid Based Complement Alternat Med , 2020 , 2020 : 4572185 . doi: 10.1155/2020/4572185 http://dx.doi.org/10.1155/2020/4572185 .
王红梅 , 李晨 , 李晓艳 , 等 . 针刺对抑郁大鼠前额叶皮层NOD样受体蛋白3炎性小体信号通路的影响 [J]. 针刺研究 , 2020 , 45 ( 10 ): 806 - 811 .
FU S , WANG J , HAO C , et al . Tetramethylpyrazine ameliorates depression by inhibiting TLR4-NLRP3 inflammasome signal pathway in mice [J]. Psychopharmacology (Berl) , 2019 , 236 ( 7 ): 2173 - 2185 .
陈颖 , 袁勇贵 . 中药单体、药对、复方、中成药治疗抑郁症研究进展 [J]. 中国临床药理学与治疗学 , 2021 , 26 ( 5 ): 586 - 593 .
张华 , 李海波 , 王继伟 . 抑郁症中医研究概况 [J]. 中医杂志 , 2006 , 47 ( 11 ): 868 - 870 .
ZHU HZ , LIANG YD , HAO WZ , et al . Xiaoyaosan exerts therapeutic effects on the colon of chronic restraint stress model rats via the regulation of immunoinflammatory activation induced by the TLR4/NLRP3 inflammasome signaling pathway [J]. Evid Based Complement Alternat Med , 2021 , 2021 : 6673538 . doi: 10.1155/2021/6673538 http://dx.doi.org/10.1155/2021/6673538 .
JIA KK , PAN SM , DING H , et al . Chaihu-shugan san inhibits inflammatory response to improve insulin signaling in liver and prefrontal cortex of CUMS rats with glucose intolerance [J]. Biomed Pharmacother , 2018 , 103 : 1415 - 1428 . doi: 10.1016/j.biopha.2018.04.171 http://dx.doi.org/10.1016/j.biopha.2018.04.171 .
王萌 . 基于线粒体自噬研究小建中汤抑制NLRP3炎症小体活化治疗抑郁症的机制 [D]. 成都 : 成都中医药大学 , 2020 .
张楠 , 许二平 , 陈玉龙 . NLRP3炎症小体与抑郁症的关系及中医药的干预作用 [J]. 中国实验方剂学杂志 , 2023 , 29 ( 3 ): 186 - 193 .
JIA KK , ZHENG YJ , ZHANG YX , et al . Banxia-houpu decoction restores glucose intolerance in CUMS rats through improvement of insulin signaling and suppression of NLRP3 inflammasome activation in liver and brain [J]. J Ethnopharmacol , 2017 , 209 : 219 - 229 . doi: 10. 1016/j.jep.2017.08.004 http://dx.doi.org/10.1016/j.jep.2017.08.004 .
JIA KK , DING H , YU HW , et al . Huanglian-wendan decoction inhibits NF-κB/NLRP3 inflammasome activation in liver and brain of rats exposed to chronic unpredictable mild stress [J]. Mediators Inflamm , 2018 , 2018 : 3093516 . doi: 10.1155/2018/3093516 http://dx.doi.org/10.1155/2018/3093516 .
陶伟伟 , 白子君 , 岳启予 , 等 . 栀子豉汤对慢性应激诱导的抑郁模型小鼠脑组织神经炎症和突触可塑性的影响 [J]. 中医杂志 , 2022 , 63 ( 11 ): 1073 - 1079 .
尚立芝 , 毛梦迪 , 许二平 , 等 . 柴胡加龙骨牡蛎汤对抑郁大鼠海马NLRP3通路的免疫调节作用 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 24 ): 33 - 39 .
赵洪庆 , 唐林 , 吴碧茹 , 等 . 百合地黄汤抑制NLRP3炎症小体激活改善焦虑性抑郁症模型大鼠海马神经元损伤 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 20 ): 7 - 14 .
王威 , 周艳艳 , 喻小明 , 等 . 四逆散对抑郁大鼠NLRP3炎症小体及抑郁样行为的作用 [J]. 中国实验方剂学杂志 , 2022 , 28 ( 12 ): 22 - 30 .
于峥 , 黄晓华 , 滕静如 , 等 . 肝主疏泄畅情志的理论内涵及临床应用 [J]. 中医杂志 , 2013 , 54 ( 22 ): 1914 - 1916 .
王伟 , 范文涛 , 王倩 . 抑郁症中药药对配伍规律探析 [J]. 吉林中医药 , 2021 , 41 ( 9 ): 1222 - 1225 .
常泽 , 韩振蕴 , 曹云松 , 等 . 基于网络药理学的柴胡-白芍药对抗抑郁作用机制研究 [J]. 中医杂志 , 2020 , 61 ( 8 ): 700 - 705 .
李添 . 基于CUMS模型大鼠大脑皮层嘌呤代谢通路的柴胡-白芍抗抑郁作用配伍机制研究 [D]. 太原 : 山西大学 , 2021 .
SU J , PAN YW , WANG SQ , et al . Saikosaponin-d attenuated lipopolysaccharide-induced depressive-like behaviors via inhibiting microglia activation and neuroinflammation [J]. Int Immunopharmacol , 2020 , 80 : 106181 . doi: 10.1016/j.intimp.2019.106181 http://dx.doi.org/10.1016/j.intimp.2019.106181 .
CHENG J , CHEN M , WAN HQ , et al . Paeoniflorin exerts antidepressant-like effects through enhancing neuronal FGF-2 by microglial inactivation [J]. J Ethnopharmacol , 2021 , 274 : 114046 . doi: 10.1016/j.jep. 2021. 114046 http://dx.doi.org/10.1016/j.jep.2021.114046 .
CAI L , MU YR , LIU MM , et al . Antidepressant-like effects of penta-acetyl geniposide in chronic unpredictable mild stress-induced depression rat model:involvement of inhibiting neuroinflammation in prefrontal cortex and regulating hypothalamic-pituitaryadrenal axis [J]. International Immunopharmacol , 2020 , 80 : 106182 . doi: 10. 1016/j.intimp.2019.106182 http://dx.doi.org/10.1016/j.intimp.2019.106182 .
CHEN H , MA Y , CHEN M , et al . Safflower extract improves depression in mice by inhibiting the TLR4-NLRP3 inflammation signaling pathway [J]. Ann Palliat Med , 2021 , 10 ( 7 ): 8015 - 8023 .
MA X , ZHU Z , GUO S , et al . The effect of deoxyschizandrin on chronic unpredictable mild stress-induced depression [J]. Biotechnol Appl Biochem , 2021 , 68 ( 1 ): 52 - 59 .
刘富群 , 高崎 , 王丹丹 , 等 . 银杏酮酯(GBE50)抑制NLRP3炎症小体活性改善大鼠抑郁样行为 [J]. 中药药理与临床 , 2017 , 33 ( 5 ): 54 - 58 .
HE MC , SHI Z , QIN M , et al . Muscone ameliorates LSP-induced depressive-like behaviors and inhibits neuroinflammation in prefrontal cortex of mice [J]. Am J Chin Med , 2020 , 48 ( 3 ): 559 - 577 .
FENG R , HE MC , LI Q , et al . Phenol glycosides extract of Fructus Ligustri Lucidi attenuated depressive-like behaviors by suppressing neuroinflammation in hypothalamus of mice [J]. Phytother Res , 2020 , 34 ( 12 ): 3273 - 3286 .
LIU L , DONG Y , SHAN X , et al . Anti-depressive effectiveness of baicalin in vitro and in vivo [J]. Molecules , 2019 , 24 ( 2 ): 326 .
XIE L , GU Z , LIU H , et al . The anti-depressive effects of hesperidin and the relative mechanisms based on the NLRP3 inflammatory signaling pathway [J]. Front Pharmacol , 2020 , 11 : 1251 . doi: 10.3389/fphar.2020.01251 http://dx.doi.org/10.3389/fphar.2020.01251 .
GENG J , LIU J , YUAN X , et al . Andrographolide triggers autophagy-mediated inflammation inhibition and attenuates chronic unpredictable mild stress (CUMS)- induced depressive-like behavior in mice [J]. Toxicol Appl Pharmacol , 2019 , 379 : 114688 . doi: 10.1016/j.taap.2019.114688 http://dx.doi.org/10.1016/j.taap.2019.114688 .
ZHANG YQ , WANG XB , XUE RR , et al . Ginsenoside Rg1 attenuates chronic unpredictable mild stress-induced depressive-like effect via regulating NF-κB/NLRP3 pathway in rats [J]. Neuroreport , 2019 , 30 ( 13 ): 893 - 900 .
ZHANG L , PREVIN R , LU L , et al . Crocin, a natural product attenuates lipopolysaccharide-induced anxiety and depressive-like behaviors through suppressing NF-κB and NLRP3 signaling pathway [J]. Brain Res Bull , 2018 , 142 : 352 - 359 . doi: 10.1016/j.brainresbull. 2018. 08.021 http://dx.doi.org/10.1016/j.brainresbull.2018.08.021 .
LI H , LIN S , QIN T , et al . Senegenin exerts anti-depression effect in mice induced by chronic un-predictable mild stress via inhibition of NF-κB regulating NLRP3 signal pathway [J]. Int Immunopharmacol , 2017 , 53 : 24 - 32 . doi: 10.1016/j.intimp.2017.10.001 http://dx.doi.org/10.1016/j.intimp.2017.10.001 .
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