药学学报, 2021, 56(3): 643-653
引用本文:
张正威, 赵朕雄, 王琰, 蒋建东. 药物基于“肠-脑”通路的研究进展[J]. 药学学报, 2021, 56(3): 643-653.
ZHANG Zheng-wei, ZHAO Zhen-xiong, WANG Yan, JIANG Jian-dong. Research progress on the interaction of neuropsychiatric drugs with the gut microbiota[J]. Acta Pharmaceutica Sinica, 2021, 56(3): 643-653.

药物基于“肠-脑”通路的研究进展
张正威1, 赵朕雄1,2, 王琰1, 蒋建东1
1. 中国医学科学院、北京协和医学院药物研究所, 北京 100050;
2. 山东第一医科大学附属肿瘤医院, 山东 济南 250024
摘要:
肠道菌群是由诸多共生及致病微生物组成的复杂而动态的群落,并与宿主紧密合作。近年来,越来越多的证据支持“肠-脑”轴理论,肠道菌群与神经精神疾病之间的联系逐步被发现。由于神经精神疾病治疗药物大多经口服后进入肠道,使得其与肠道菌群可能产生更广泛的相互作用。多项研究表明该类药物可改变肠道菌群的组成和功能,同时肠道菌群也会参与药物的代谢,进而对脑功能产生有益或有害的影响。因此,肠道菌群在药物代谢中的作用越来越受到关注。本文综述了国内外有关两者相互作用的研究结果,探讨了神经精神疾病对肠道菌群的影响以及肠道菌群对潜在精神活性药物的作用机制,为临床各类神经精神疾病可能的治疗方案提供了新的思路。
关键词:    肠道菌群      神经精神疾病      药物代谢      “肠-脑”轴      相互作用     
Research progress on the interaction of neuropsychiatric drugs with the gut microbiota
ZHANG Zheng-wei1, ZHAO Zhen-xiong1,2, WANG Yan1, JIANG Jian-dong1
1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
2. The Affiliated Tumor Hospital of Shandong First Medical University, Jinan 250024, China
Abstract:
The gut microbiota is an intricate and dynamic community composed of many symbiotic and pathogenic microorganisms, and works closely with the host. In recent years increasing evidence has supported the gut-brain axis theory, lending support for a link between gut microbiota and neuropsychiatric diseases. Since most of the drugs used to treat neuropsychiatric diseases enter the intestinal tract after oral administration, interaction with the gut microbiota is likely. A number of studies have shown that such drugs can change the composition and function of the gut microbiota. At the same time, the gut microbiota also participates in the metabolism of drugs, which in turn have beneficial or harmful effects on brain function. Therefore, the role of gut microbiota in drug metabolism also has attracted attention. This article reviews the research results of the interaction between the two, discusses the influence of neuropsychiatric diseases on the gut microbiota and the effect of the gut microbiota on psychoactive drugs, and provides new ideas for the treatment of various clinical neuropsychiatric diseases.
Key words:    gut microbiota    neuropsychiatric disease    drug metabolism    gut-brain axis    interaction   
收稿日期: 2020-09-29
DOI: 10.16438/j.0513-4870.2020-1516
基金项目: 国家创新药物重大专项(2018ZX09711001-002-002);国家自然科学基金(81573493);北京市自然科学基金重点项目(7181007);北京市创新药物非临床药物代谢及药代/药效研究重点实验室(Z141102004414062);中国医学科学院医学与健康科技创新工程项目(2016-I2M-3-011).
通讯作者: 王琰,Tel:86-10-63165238,E-mail:wangyan@imm.ac.cn;蒋建东,Tel:86-10-83160005,E-mail:jiang.jdong@163.com
Email: wangyan@imm.ac.cn;jiang.jdong@163.com
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参考文献:
[1] Thursby E, Juge N. Introduction to the human gut microbiota[J]. Biochem J, 2017, 474:1823-1836.
[2] Mayer EA, Knight R, Mazmanian SK, et al. Gut microbes and the brain:paradigm shift in neuroscience[J]. J Neurosci, 2014, 34:15490-15496.
[3] Critchfield JW, van Hemert S, Ash M, et al. The potential role of probiotics in the management of childhood autism spectrum disorders[J]. Gastroenterol Res Pract, 2011, 2011:161358.
[4] Dellagioia N, Hannestad J. A critical review of human endotoxin administration as an experimental paradigm of depression[J]. Neurosci Biobehav Rev, 2010, 34:130-143.
[5] Forsythe P, Sudo N, Dinan T, et al. Mood and gut feelings[J]. Brain Behav Immun, 2010, 24:9-16.
[6] Grenham S, Clarke G, Cryan JF, et al. Brain-gut-microbe communication in health and disease[J]. Front Physiol, 2011, 2:94.
[7] Dash S, Clarke G, Berk M, et al. The gut microbiome and diet in psychiatry:focus on depression[J]. Curr Opin Psychiatry, 2015, 28:1-6.
[8] Cryan JF, Dinan TG. Gut microbiota:microbiota and neuroimmune signalling-Metchnikoff to microglia[J]. Nat Rev Gastroenterol Hepatol, 2015, 12:494-496.
[9] Sherwin E, Sandhu KV, Dinan TG, et al. May the force be with you:the light and dark sides of the microbiota-gut-brain axis in neuropsychiatry[J]. CNS Drugs, 2016, 30:1019-1041.
[10] Giada DP, Stephen MC, Premysl B. The microbiota-gut-brain axis in functional gastrointestinal disorders[J]. Gut Microbes, 2014, 5:419-429.
[11] Jänig W.Integrative Action of the Autonomic Nervous System:Neurobiology of Homeostasis[M]. Cambridge, UK:Cambridge University Press, 2006.
[12] Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota[J]. J Clin Invest, 2015, 125:926-938.
[13] Maier TV, Lucio M, Lee LH, et al. Impact of dietary resistant starch on the human gut microbiome, metaproteome, and metabolome[J]. mBio, 2017, 8:e01343-17.
[14] Rhee SH, Pothoulakis C, Mayer EA. Principles and clinical implications of the braingut-enteric microbiota axis[J]. Nat Rev Gastroenterol Hepatol, 2009, 6:306-314.
[15] Chey WY, Jin HO, Lee MH, et al. Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea[J]. Am J Gastroenterol, 2001, 96:1499-1506.
[16] Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders[J]. Cell, 2013, 155:1451-1463.
[17] Lyte M. Microbial endocrinology in the microbiome-gut-brain axis:how bacterial production and utilization of neurochemicals influence behavior[J]. PLoS Pathog, 2013, 9:e1003726.
[18] Sokol H, Adolph TE. The microbiota:an underestimated actor in radiation-induced lesions?[J]. Gut, 2018, 67:1-2.
[19] Wall R, Cryan JF, Ross RP, et al. Bacterial neuroactive compounds produced by psychobiotics[J]. Adv Exp Med Biol, 2014, 817:221-239.
[20] Chen K, Luan X, Liu Q, et al. Drosophila histone demethylase KDM5 regulates social behavior through immune control and gut microbiota maintenance[J]. Cell Host Microbe, 2019, 25:537-552.
[21] Schretter CE, Vielmetter J, Bartos I, et al. A gut microbial factor modulates locomotor behaviour in Drosophila[J]. Nature, 2018, 563:402-406.
[22] Kim YK, Cheolmin S. The microbiota-gut-brain axis in neuropsychiatric disorders:pathophysiological mechanisms and novel treatments[J]. Curr Neuropharmacol, 2018, 16:559-573.
[23] Jacinta W, Brendan TG, Gerard C, et al. Drug-gut microbiota interactions:implications for neuropharmacology[J]. Br J Pharmacol, 2018, 175:4415-4429.
[24] Mac QG, Surette M, Moayyedi P. The gut microbiota and psychiatric illness[J]. J Psychiatry Neurosci, 2017, 42:75-77.
[25] Desbonnet L, Clarke G, Shanahan F, et al. Microbiota is essential for social development in the mouse[J]. Mol Psychiatry, 2014, 19:146-148.
[26] Finegold SM, Dowd SE, Gontcharova V, et al. Pyrosequencing study of fecal microflora of autistic and control children[J]. Anaerobe, 2010, 16:444-453.
[27] Tomova A, Husarova V, Lakatosova S, et al. Gastrointestinal microbiota in children with autism in Slovakia[J]. Physiol Behav, 2015, 138:179-187.
[28] Erdman SE, Poutahidis T. Microbes and oxytocin:benefits for host physiology and behavior[J]. Int Rev Neurobiol, 2016, 131:91-126.
[29] Dinan TG, Cryan JF. Melancholic microbes:a link between gut microbiota and depression?[J]. Neurogastroenterol Motil, 2013, 25:713-719.
[30] Davis DJ, Patrick MH, Eldin J, et al. Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice[J]. Brain Behav Immun, 2017, 59:38-48.
[31] Aizawa E, Tsuji H, Asahara T, et al. Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder[J]. J Affect Disord, 2016, 202:254-257.
[32] Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder[J]. Brain Behav Immun, 2015, 48:186-194.
[33] Kelly JR, Borre Y, O'Brien C, et al. Transferring the blues:depression-associated gut microbiota induces neurobehavioural changes in the rat[J]. J Psychiatr Res, 2016, 82:109-118.
[34] Gaykema RP, Goehler LE, Lyte M. Brain response to cecal infection with Campylobacter jejuni:analysis with Fos immunohistochemistry[J]. Brain Behav Immun, 2004, 18:238-245.
[35] Lyte M, Li W, Opitz N, et al. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium[J]. Physiol Behav, 2006, 89:350-357.
[36] Pistollato F, Sumalla CS, Elio I, et al. Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer's disease[J]. Nutr Rev, 2016, 74:624-634.
[37] Scheperjans F, Aho V, Pereira PA, et al. Gut microbiota are related to Parkinson's disease and clinical phenotype[J]. Mov Disord, 2015, 30:350-358.
[38] Lee H M, Kim Y. Drug repurposing is a new opportunity for developing drugs against neuropsychiatric disorders[J]. Schizophr Res Treatment, 2016, 2016:6378137.
[39] Asano Y, Tetsuya H, Ryo N, et al. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice[J]. Am J Physiol Gastrointest Liver Physiol, 2012, 303:G1288-G1295.
[40] William RW, Andrew TA, Jun L, et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites[J]. Proc Natl Acad Sci U S A, 2009, 106:3698-3703.
[41] Mudd AT, Berding K, Wang M, et al. Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig[J]. Gut Microbes, 2017, 8:589-600.
[42] Mitsuharu M, Ryoko K, Takushi O, et al. Cerebral low-molecular metabolites influenced by intestinal microbiota:a pilot study[J]. Front Syst Neurosci, 2013, 7:9.
[43] Philip S. Neurotransmitter modulation by the gut microbiota[J]. Brain Res, 2018, 1693(Pt B):128-133.
[44] Munoz-bellido JL, Munoz-criado S, Garcia-Rodriguez JA. Antimicrobial activity of psychotropic drugs:selective serotonin reuptake inhibitors[J]. Int J Antimicrob Agents, 2000, 14:177-180.
[45] Munoz-bellido JL, Munoz-criado S, Garcia-rodriguez JA. In-vitro activity of psychiatric drugs against Corynebacterium urealyticum (Corynebacterium group D2)[J]. J Antimicrob Chemother, 1996, 37:1005-1009.
[46] Mandal A, Sinha C, Kumar JA, et al. An investigation on in vitro and in vivo antimicrobial properties of the antidepressant:amitriptyline hydrochloride[J]. Braz J Microbiol, 2010, 41:635-645.
[47] Molnar J. Antiplasmid activity of tricyclic compounds[J]. Methods Find Exp Clin Pharmacol, 1988, 10:467-474.
[48] Macedo D, Filho AJ MC, Soares de Sousa CN, et al. Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness[J]. J Affect Disord, 2017, 208:22-32.
[49] Csiszar K, Molnar J. Mechanism of action of tricyclic drugs on Escherichia coli and Yersinia enterocolitica plasmid maintenance and replication[J]. Anticancer Res, 1992, 12:2267-2272.
[50] Cussotto S, Clarke G, Dinan TG, et al. Psychotropics and the microbiome:a chamber of secrets[J]. Psychopharmacology (Berl), 2019, 236:1411-1432.
[51] Hahn BL, Sohnle PG. Effect of thioridazine on experimental cutaneous staphylococcal infections[J]. In vivo, 2014, 28:33-38.
[52] Dastidar SG, Chaudhury A, Annadurai S, et al. In vitro and in vivo antimicrobial action of fluphenazine[J]. J Chemother, 1995, 7:201-206.
[53] Mazumder R, Ganguly K, Dastidar SG, et al. Trifluoperazine:a broad spectrum bactericide especially active on staphylococci and vibrios[J]. Int J Antimicrob Agents, 2001, 18:403-406.
[54] Rani BL, Mazumdar K, Dutta NK, et al. Antibacterial property of the antipsychotic agent prochlorperazine, and its synergism with methdilazine[J]. Microbiol Res, 2005, 160:95-100.
[55] Grimsey EM, Fais C, Marshall RL, et al. Chlorpromazine and amitriptyline are substrates and inhibitors of the AcrB multidrug efflux pump[J]. mBio, 2020, 11:e00465-20.
[56] Davey KJ, Cotter PD, O'Sullivan O, et al. Antipsychotics and the gut microbiome:olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat[J]. Transl Psychiatry, 2013, 3:e309.
[57] Cussotto S, Strain CR, Fouhy F, et al. Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function[J]. Psychopharmacology, 2019, 236:1671-1685.
[58] Iva L, Dmitriy G, Oren Z, et al. Antidepressants affect gut microbiota and Ruminococcus flavefaciens is able to abolish their effects on depressive-like behavior[J]. Transl Psychiatry, 2019, 9:133.
[59] Ticinesi A, Milani C, Lauretani F, et al. Gut microbiota composition is associated with polypharmacy in elderly hospitalized patients[J]. Sci Rep, 2017, 7:11102.
[60] Flowers SA, Evans SJ, Ward KM, et al. Interaction between atypical antipsychotics and the gut microbiome in a bipolar disease cohort[J]. Pharmacotherapy, 2017, 37:261-267.
[61] Flowers SA, Baxter NT, Ward KM, et al. Effects of atypical antipsychotic treatment and resistant starch supplementation on gut microbiome composition in a cohort of patients with bipolar disorder or schizophrenia[J]. Pharmacotherapy, 2019, 39:161-170.
[62] Bahr SM, Tyler BC, Wooldridge N, et al. Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children[J]. Transl Psychiatry, 2015, 5:e652.
[63] McGovern AS, Hamlin AS, Winter G. A review of the antimicrobial side of antidepressants and its putative implications on the gut microbiome[J]. Aust N Z J Psychiatry, 2019, 53:1151-1166.
[64] Falony G, Joossens M, Vieira-silva S, et al. Population-level analysis of gut microbiome variation[J]. Science, 2016, 352:560-564.
[65] Sudeepa B, Ahmed TA, Matthias A, et al. Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients[J]. Transl Psychiatry, 2019, 9:173.
[66] Bennett PN, Brown MJ. Clinical Pharmacology[M]. 10th Ed. London & New York:Church Hill Livingstone Elsevier, 2008:74-114.
[67] Moda-sava RN, Murdock MH, Parekh PK, et al. Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation[J]. Science, 2019, 364:eaat8078.
[68] Bruk G, Joseph IA, Richard SS, et al. Ketamine interactions with gut-microbiota in rats:relevance to its antidepressant and anti-inflammatory properties[J]. BMC Microbiol, 2018, 18:222.
[69] Huang NN, Hua DY, Zhan GF, et al. Role of actinobacteria and coriobacteriia in the antidepressant effects of ketamine in an inflammation model of depression[J]. Pharmacol Biochem Behav, 2019, 176:93-100.
[70] Yang C, Qu YG, Fujita Y, et al. Possible role of the gut microbiota-brain axis in the antidepressant effects of (R)-ketamine in a social defeat stress model[J]. Transl Psychiatry, 2017, 7:1294.
[71] Morgan AP, Crowley JJ, Nonneman RJ, et al. The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse[J]. PLoS One, 2014, 9:e115225.
[72] Davey KJ, O'Mahony SM, Schellekens H, et al. Gender-dependent consequences of chronic olanzapine in the rat:effects on body weight, inflammatory, metabolic and microbiota parameters[J]. Psychopharmacology, 2012, 221:155-169.
[73] Sarah MB, Benjamin JW, Ana NC, et al. Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure[J]. EBioMedicine, 2015, 2:1725-1734.
[74] Lyte M, Daniels KM, Schmitz-Esser S, et al. Fluoxetine-induced alteration of murine gut microbial community structure:evidence for a microbial endocrinology-based mechanism of action responsible for fluoxetine-induced side effects[J]. PeerJ, 2019, 7:e6199.
[75] Fung TC, Vuong HE, Luna Cristopher DG, et al. Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut[J]. Nat Microbiol, 2019, 4:2064-2073.
[76] Liu F, Horton-sparks K, Hull V, et al. The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism[J]. Mol Autism, 2018, 9:61.
[77] de Theije CG, Wopereis H, Ramadan M, et al. Altered gut microbiota and activity in a murine model of autism spectrum disorders[J]. Brain Behav Immun, 2014, 37:197-206.
[78] de Theije CG, Koelink PJ, Korte-bouws GA, et al. Intestinal inflammation in a murine model of autism spectrum disorders[J]. Brain Behav Immun, 2014, 37:240-247.
[79] Anouschka SR, Eldin J, Danielle JH, et al. Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression[J]. Gut Microbes, 2020, 11:735-753.
[80] Elmer GW, Remmel RP. Role of the intestinal microflora in clonazepam metabolism in the rat[J]. Xenobiotica, 1984, 14:829-840.
[81] Rafii F, Sutherland JB, Hansen Jr EB, et al. Reduction of nitrazepam by clostridium leptum, a nitroreductase-producing bacterium isolated from the human intestinal tract[J]. Clin Infect Dis, 1997, 25:S121-S122.
[82] Takeno S, Sakai T. Involvement of the intestinal microflora in nitrazepam-induced teratogenicity in rats and its relationship to nitroreduction[J]. Teratology, 1991, 44:209-214.
[83] Myles RM, Zhang C, Vanessa L, et al. Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer's disease[J]. Sci Rep, 2016, 6:30028.
[84] DiCarlo G, Wilcock D, Henderson D, et al. Intrahippocampal LPS injections reduce Aβ load in APP+PS1 transgenic mice[J]. Neurobiol Aging, 2001, 22:1007-1012.
[85] Donna LH, Mary M, Lisa MR, et al. Microglial activation is required for Aβ clearance after intracranial injection of lipopolysaccharide in APP transgenic mice[J]. J Neuroimmune Pharmacol, 2007, 2:222-231.
[86] Wang XY, Sun GQ, Feng T, et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression[J]. Cell Res, 2019, 29:787-803.
[87] Hu MM, Zheng P, Xie YY, et al. Propionate protects haloperidol-induced neurite lesions mediated by neuropeptide Y[J]. Front Neurosci, 2018, 12:743.
[88] Zhu HZ, Liang YD, Ma QY, et al. Xiaoyaosan improves depressive-like behavior in rats with chronic immobilization stress through modulation of the gut microbiota[J]. Biomed Pharmacother, 2019, 112:108621.
[89] Wang X, Feng Q, Xiao Y, et al. Radix Bupleuri ameliorates depression by increasing nerve growth factor and brain-derived neurotrophic factor[J]. Int J Clin Exp Med, 2015, 8:9205-9217.
[90] Chen XQ, Chen SJ, Liang WN, et al. Saikosaponin A attenuates perimenopausal depression-like symptoms by chronic unpredictable mild stress[J]. Neurosci Lett, 2018, 662:283-289.
[91] Gong WX, Zhou YZ, Li X, et al. Research progress in antidepressive active ingredients and pharmacological effects of Angelicae Sinensis Radix[J]. Chin Tradit Herb Drugs (中草药), 2016, 47:3905-3911.
[92] Liao MN, Yu LJ, Zhang YP, et al. Antidepressant-like effect of cell-free filtrate of sodium ferulate-induced and differentioned PC12 cell lysates[J]. Chin J Cell Biol (中国细胞生物学学报), 2011, 33:608-621.
[93] Qi RG, Liu HH, Qian X. Observation on the therapeutic effect of butylphthalide for the patients with post storke depression[J]. Clin Med Eng (临床医学工程), 2012, 19:1941-1942.
[94] Deng SX, Chen SN, Yao P, et al. Serotonergic activity-guided phytochemical investigation of the roots of Angelica sinensis[J]. J Nat Prod, 2006, 69:536-541.
[95] Zhao ZY, Wang WX, Guo ZH, et al. Anti-depressive effect of liquiritin on chronic stress depression in rats[J]. Chin J Clin Rehabil (中国临床康复), 2006, 10:69-72.
[96] Li X, Gong WX, Zhou YZ, et al. Research progress on antidepressive active ingredients of Xiaoyaosan and their mechanism[J]. Chin Tradit Herb Drugs (中草药), 2015, 46:3109-3116.
[97] Gong WX, Zhou YZ, Qin XM, et al. Application of atractylenolide in preparation of antidepressant drug:CN, 105582006A[P]. 2016-05-18.
[98] Xue JS, Li HY, Fu Q, et al. Antidepressant-like effects of L-menthone in depressed mice and its possible mechanisms[J]. Pharm Clin Res (药学与临床研究), 2015, 23:238-241.
[99] Ma X, Zhao YL, Zhu Y, et al. Paeonia lactiflora Pall. protects against ANIT-induced cholestasis by activating Nrf2via PI3K/Akt signaling pathway[J]. Drug Des Devel Ther, 2015, 9:5061-5074.
[100] Wang QS, Gao T, Cui YL, et al. Comparative studies of paeoniflorin and albiflorin from Paeonia lactiflora on anti-inflammatory activities[J]. Pharm Biol, 2014, 52:1189-1195.
[101] Wang YL, Wang JX, Hu XX, et al. Antidepressant-like effects of albiflorin extracted from Radix Paeoniae Alba[J]. J Ethnopharmacol, 2016, 179:9-15.
[102] Zhu X, Jing L, Chen C, et al. Danzhi Xiaoyao San ameliorates depressive-like behavior by shifting toward serotonin via the downregulation of hippocampal indoleamine 2,3-dioxygenase[J]. J Ethnopharmacol, 2015, 160:86-93.
[103] Qiu Z K, He JL, Liu X, et al. Anti-PTSD-like effects of albiflorin extracted from Radix Paeoniae Alba[J]. J Ethnopharmacol, 2017, 198:324-330.
[104] Zhang JJ, Wang JX, Li W, et al. Study on the antidepressant-like effect of albiflorin[J]. Pharm Clin Chin Mater Med (中药与临床), 2011, 2:35-37.
[105] Zhao ZX. Preclinical Pharmacokinetic Study of Albiflorin (芍药内酯苷临床前药代动力学研究)[D]. Jinan:University of Jinan, 2015.
[106] Yu JB, Zhao ZX, Peng R, et al. Gut microbiota-based pharmacokinetics and the antidepressant mechanism of paeoniflorin[J]. Front Pharmacol, 2019, 10:268.
[107] Zhao ZX, Fu J, Ma SR, et al. Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin[J]. Theranostics, 2018, 8:5945-5959.
[108] Kong WJ, Wei J, Abidi P, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins[J]. Nat Med, 2004, 10:1344-1351.
[109] Derosa G, D'Angelo A, Bonaventura A, et al. Effects of berberine on lipid profile in subjects with low cardiovascular risk[J]. Expert Opin Biol Ther, 2013, 13:475-482.
[110] Lee YS, Kim WS, Kim KH, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states[J]. Diabetes, 2006, 55:2256-2264.
[111] Kong WJ, Zhang H, Song DQ, et al. Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression[J]. Metabolism, 2009, 58:109-119.
[112] Durairajan SSK, Liu LF, Lu JH, et al. Berberine ameliorates-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model[J]. Neurobiol Aging, 2012, 33:2903-2919.
[113] Patil S, Tawari S, Mundhada D, et al. Protective effect of berberine, an isoquinoline alkaloid ameliorates ethanol-induced oxidative stress and memory dysfunction in rats[J]. Pharmacol Biochem Behav, 2015, 136:13-20.
[114] Kim M, Cho KH, Shin MS, et al. Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson's disease[J]. Int J Mol Med, 2014, 33:870-878.
[115] Kwon IH, Choi HS, Shin KS, et al. Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson's disease[J]. Neurosci Lett, 2010, 486:29-33.
[116] Tan XS, Ma JY, Feng R, et al. Tissue distribution of berberine and its metabolites after oral administration in rats[J]. PLoS One, 2013, 8:e77969.
[117] Liu YT, Hao HP, Xie HG, et al. Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats[J]. Drug Metab Dispos, 2010, 38:1779-1784.
[118] Feng R, Shou JW, Zhao ZX, et al. Transforming berberine into its intestine-absorbable form by the gut microbiota[J]. Sci Rep, 2015, 5:12155.
[119] Vayu MR, Elizabeth NB, Jordan EB, et al. Discovery and inhibition of an interspecies gut bacterial pathway for levodopa metabolism[J]. Science, 2019, 364:eaau6323.
[120] Connolly BS, Lang AE. Pharmacological treatment of Parkinson's disease:a review[J]. JAMA, 2014, 311:1670-1683.
[121] Grundmann O, Nakajima J, Kamata K, et al. Kaempferol from the leaves of Apocynum venetum possesses anxiolytic activities in the elevated plus maze test in mice[J]. Phytomedicine, 2009, 16:295-302.
[122] Cica V, Karen N, Olaf K, et al. Route of administration determines the anxiolytic activity of the flavonols kaempferol, quercetin and myricetin-are they prodrugs?[J]. J Nutr Biochem, 2012, 23:733-740.
[123] Chi L, Khan I, Lin ZB, et al. Fructo-oligosaccharides from Morinda officinalis remodeled gut microbiota and alleviated depression features in a stress rat model[J]. Phytomedicine, 2020, 67:153157.
[124] Li Y, Peng Y, Ma P, et al. Antidepressant-like effects of cistanche tubulosa extract on chronic unpredictable stress rats through restoration of gut microbiota homeostasis[J]. Front Pharmacol, 2018, 9:967.
[125] Zhou HX, Tai JJ, Xu HY, et al. Xanthoceraside could ameliorate Alzheimer's disease symptoms of rats by affecting the gut microbiota composition and modulating the endogenous metabolite levels[J]. Front Pharmacol, 2019, 10:1035.
[126] Guo Y, Xie JP, Li X, et al. Antidepressant effects of rosemary extracts associate with anti-inflammatory effect and rebalance of gut microbiota[J]. Front Pharmacol, 2018, 9:1126.
[127] Wang S, Jiang W, Ouyang T, et al. Jatrorrhizine balances the gut microbiota and reverses learning and memory deficits in APP/PS1 transgenic mice[J]. Sci Rep, 2019, 9:19575.
[128] Zmora N, Zilberman-Schapira G, Suez J, et al. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features[J]. Cell, 2018, 174:1388-1405.
[129] Lakhan SE, Vieira KF. Nutritional therapies for mental disorders[J]. Nutr J, 2008, 7:2.
[130] Lang UE, Beglinger C, Schweinfurth N, et al. Nutritional aspects of depression[J]. Cell Physiol Biochem, 2015, 37:1029-1043.
[131] Owen L, Corfe B. The role of diet and nutrition on mental health and wellbeing[J]. Proc Nutr Soc, 2017, 76:425-426.
[132] Jacka FN. Nutritional psychiatry:where to next?[J]. EbioMedicine, 2017, 17:24-29.
[133] Clarke SF, Murphy EF, O'Sullivan O, et al. Exercise and associated dietary extremes impact on gut microbial diversity[J]. Gut, 2014, 63:1913-1920.
[134] Schnorr SL, Bachner HA. Integrative therapies in anxiety treatment with special emphasis on the gut microbiome[J]. Yale J Biol Med, 2016, 89:397-422.
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