Subscribe to RSS
DOI: 10.1055/a-1068-9686
Antidepressant Effects and Mechanisms of the Total Iridoids of Valeriana jatamansi on the Brain-Gut Axis
Supported by: Sichuan Province Academic and Technical Leaders Cultivate Support Funds, the Key Project of Research and Development Plan of Science and Technology Department of Sichuan Province 2018SZ0078Supported by: Sichuan Province Academic and Technical Leaders Cultivate Support Funds, the Key Project of Research and Development Plan of Science and Technology Department of Sichuan Province 2018ZR0368
Supported by: the Research funds of Chengdu science and technology office 2015-HM01-00347-SF
Supported by: the Research funds of Sichuan traditional Chinese medicine administration 2016Q040
Publication History
received 24 July 2019
revised 15 November 2019
accepted 15 November 2019
Publication Date:
04 December 2019 (online)
Abstract
Valeriana jatamansi is widely used in Chinese folk medicine and contains iridoids as important active ingredients. The brain-gut axis describes a complex bidirectional system between the central nervous system and the gastrointestinal tract. Herein, we evaluated the antidepressant effects of total iridoids of Valeriana jatamansi (TIV) and preliminarily investigated the effects of gut microbiota on their antidepressant effects using a chronic, unpredictable mild-stress mouse model. Mice were given 5.7, 11.4, or 22.9 mg/kg TIV for 1 week. Fluoxetine (2.6 mg/kg) served as a positive control. Body weight was measured, and behavioral tests including SPT and TST were applied. Colon pathology was assessed through hematoxylin-eosin staining. Additionally, levels of serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE), substance P (SP) and corticotropin-releasing factor (CRF) in the hippocampus and colon were measured by ELISA. In addition, 16SrRNA gene sequencing was performed to explore changes in intestinal microbiota richness and diversity. Our results demonstrated that the model group showed significant depression-like behavior, while the fluoxetine group showed improved depression-like symptoms; after administration, TIV increased body weight, sucrose solution consumption, and ameliorated depression-like behaviors. The overall cell degeneration in colons also improved. In addition, TIV modulated the levels of 5-HT, NE, SP, and CRF expression in the hippocampus and colon. The diversity and richness of gut microbes increased compared to the model group. We therefore conclude that the antidepressant effects of TIV may be related to gut flora structures and regulation of 5-HT, NE, SP, and CRF in the brain and intestine.
-
References
- 1 Li SZ. Compendium of Materia Medica. 1st ed.. ed. China Radio International Press: Beijing, China; 1994: 1639-1643
- 2 Schwabe C. Chemistry and biodiversity. Chem Biodivers 2010; 1: 1584-1587
- 3 Pei QY, Xuan LI, Zhu JX, Chao-Ying MA. Advances in study on pharmacological action and mechanism of Valeriana wallichii DC. Chinese Arch Tradit Chinese Med 2010; 9: 1864-1865
- 4 Ernst E. Scientific basis for ayurvedic therapies. Focus Altern Complement Ther 2010; 9: 243
- 5 Bhattacharyya D, Jana U, Debnath PK, Sur TK. Initial exploratory observational pharmacology of Valeriana wallichii on stress management: a clinical report. Nepal Med Coll J 2007; 9: 36-39
- 6 Fazal S, Nasiara K, Hassan GA, Sewell RDE. Terpenoid content of Valeriana wallichii extracts and antidepressant-like response profiles. Phyther Res 2010; 24: 686-691
- 7 Sah SP, Mathela CS, Chopra K. Involvement of nitric oxide (NO) signalling pathway in the antidepressant activity of essential oil of Valeriana wallichii Patchouli alcohol chemotype. Phytomedicine 2011; 18: 1269-1275
- 8 Ahmed HU, Hossain MD, Aftab A, Soron TR, Alam MT, Chowdhury MWA, Uddin A. Suicide and depression in the World Health Organization South-East Asia region: a systematic review. WHO South-East Asia J public Heal 2017; 6: 60
- 9 Ghanean H, Ceniti AK, Kennedy SH. Fatigue in patients with major depressive disorder: prevalence, burden and pharmacological approaches to management. CNS Drugs 2018; 32: 65-74
- 10 Srikumar BN, Paschapur M, Kalidindi N, Adepu B, Das ML, Sreedhara MV, Kuchibhotla VK, Pieschl RL, Li YW, Dsp E. Characterization of the adrenocorticotrophic hormone-induced mouse model of resistance to antidepressant drug treatment. Pharmacol Biochem Behav 2017; 161: 53
- 11 Cryan JF, OʼMahony SM. The microbiome-gut-brain axis: from bowel to behavior. Neurogastroenterol Motil 2011; 23: 187-192
- 12 Collins SM, Michael S, Premysl B. The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 2012; 10: 735
- 13 Quigley EMM. Microbiota-brain-gut axis and neurodegenerative diseases. Curr Neurol Neurosci Rep 2017; 17: 94
- 14 Keita AV, Ericson AC, Braaf Y, Wallon C, Söderholm JD. Increased antigen and bacterial uptake in follicle associated epithelium induced by chronic psychological stress in rats. Gut 2004; 53: 494-500
- 15 Wang GH, Dong HY, Dong WG, Wang XP, Luo HS, Yu JP, Wang GH, Dong HY, Dong WG, Wang XP. Protective effect of Radix Acanthopanacis Senticosi capsule on colon of rat depression model. World J Gastroenterol 2005; 11: 1373-1377
- 16 Marathe SV, DʼAlmeida PL, Virmani G, Bathini P, Alberi L. Effects of monoamines and antidepressants on astrocyte physiology: implications for monoamine hypothesis of depression. J Exp Neurosci 2018; 12: 117906951878914
- 17 Gardier AM. Antidepressant activity: contribution of brain microdialysis in knock-out mice to the understanding of BDNF/5-HT transporter/5-HT autoreceptor interactions. Front Pharmacol 2013; 4: 98
- 18 Bravo JA, Dinan TG, Cryan JF. Alterations in the central CRF system of 2 different rat models of comorbid depression and functional gastrointestinal disorders. Int J Neuropsychopharmacol 2011; 14: 666-683
- 19 Oleskin AV, Elʼ-Registan GI, Shenderov BA. Role of neuromediators in the functioning of the human microbiota: “business talks” among microorganisms and the microbiota-host dialogue. Mikrobiologiia 2016; 85: 3-25
- 20 Nemeroff CB, Widerlöv E, Bissette G, Walléus H, Karlsson I, Eklund K, Kilts CD, Loosen PT, Vale W. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 1984; 226: 1342-1344
- 21 Rao M, Gershon M. Bugs, guts, and glia: how microbiota influence enteric gliogenesis and migration. Neuron 2015; 85: 229-230
- 22 Pokusaeva K, Johnson C, Luk B, Uribe G, Fu Y, Oezguen N, Matsunami RK, Lugo M, Major A, Mori-Akiyama Y. GABA-producing bifidobacterium dentiummodulates visceral sensitivity in the intestine. Neurogastroenterol Motil 2017; 29
- 23 Tsavkelova EA, Botvinko IV, Kudrin VS, Oleskin AV. Detection of neurotransmitter amines in microorganisms with the use of high-performance liquid chromatography. Dokl Biochem 2000; 372: 115-117
- 24 Tannock GW, Savage DC. Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract. Infect Immun 1974; 9: 591-598
- 25 Moreau JL. Validation of an animal model of anhedonia, a major symptom of depression. Lencéphale 1997; 23: 280
- 26 OʼMahony SM, Marchesi JR, Scully P, Codling C, Ceolho AM, Quigley EMM, Cryan JF, Dinan TG. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 2009; 65: 263-267
- 27 Gootenberg DB, Turnbaugh PJ. Companion animals symposium: humanized animal models of the microbiome. J Anim Sci 2011; 89: 1531-1537
- 28 Gareau MG, Wine E, Rodrigues DM, Cho JH, Whary MT, Philpott DJ, Macqueen G, Sherman PM. Bacterial infection causes stress-induced memory dysfunction in mice. Gut 2011; 60: 307-317
- 29 Desbonnet L, Clarke G, Shanahan F, Dinan TG, Cryan JF. Microbiota is essential for social development in the mouse. Mol Psychiatry 2014; 19: 146-148
- 30 Naseribafrouei A, Hestad K, Avershina E, Sekelja M, Linløkken A, Wilson R, Rudi K. Correlation between the human fecal microbiota and depression. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc 2014; 26: 1155-1162
- 31 Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG. Minireview: gut microbiota: the neglected endocrine organ. Mol Endocrinol 2014; 28: 1221-1238
- 32 OʼMahony SM, Hyland NP, Dinan TG, Cryan JF. Maternal separation as a model of brain-gut axis dysfunction. Psychopharmacology (Berl) 2011; 214: 71-88
- 33 Maes M, Kubera M, Leunis JC, Berk M. Increased IgA and IgM responses against gut ommensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. J Affect Disord 2012; 141: 55-62
- 34 Bueno L, de Ponti F, Fried M, Kullak-Ublick GA, Kwiatek MA, Pohl D, Quigley EMM, Tack J, Talley NJ. Serotonergic and non-serotonergic targets in the pharmacotherapy of visceral hypersensitivity. Neurogastroenterol Motil 2010; 19: 89-119
- 35 Park AJ, Collins J, Blennerhassett PA, Ghia JE, Verdu EF, Bercik P, Collins SM. Altered colonic function and microbiota profile in a mouse model of chronic depression. Neurogastroenterol Motil 2013; 25: 733-e575
- 36 Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res 2015; 63: 1-9
- 37 Sherwin E, Rea K, Dinan TG, Cryan JF. A gut (microbiome) feeling about the brain. Curr Opin Gastroenterol 2016; 32: 96-102
- 38 Li SH. Studies on Separation and Antianxiety Activity of Iridoids effective Fraction of Valeriana Jatamansi Jones [M. S. Thesis]. Chengdu China: Southwest Jiaotong University; 2013
- 39 Biala G, Pekala K, Boguszewska-Czubara A, Michalak A, Kruk-Slomka M, Budzynska B. Behavioral and biochemical interaction between nicotine and chronic unpredictable mild stress in mice. Mol Neurobiol 2017; 54: 904-921
- 40 Zhang H, Zhou Z, Chen Z, Zhong Z, Li Z. Ginsenoside Rg3 exerts anti-depressive effect on an NMDA-treated cell model and a chronic mild stress animal model. J Pharmacol Sci 2017; 134: 45-54
- 41 Sun J, Wang F, Hong G, Pang M, Xu H, Li H, Tian F, Fang R, Yao Y, Liu J. Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress. Neurosci Lett 2016; 618: 159-166