Advertisement

Combination of Geniposide and Eleutheroside B Exerts Antidepressant-like Effect on Lipopolysaccharide-Induced Depression Mice Model

  • Bo Zhang
  • Hong-sheng Chang
  • Kai-li Hu
  • Xue Yu
  • Li-na Li
  • Xiang-qing XuEmail author
Original Article
  • 11 Downloads

Abstract

Objective

To study the antidepressant-like effect and action mechanism of geniposide and eleutheroside B combination treatment on the lipopolysaccharide (LPS)-induced depression mice model.

Methods

Depression mice model was established by lipopolysaccharide (LPS) injection. Totally 48 mice were randomly divided into 6 groups (8 rats per group) according to a random number table, including normal, model, fluoxetine (20 mg/kg), geniposide (100 mg/kg) + eleutheroside B (100 mg/kg), geniposide + eleutheroside B + WAY 100635 (0.03 mg/kg), geniposide + eleutheroside B+ N-methyl-D-aspartic acid receptor (NMDA, 75 mg/kg) groups, respectively. After continuous administration for 10 days, autonomic activity tests after 30 min of administration were performed on the 10th day. On the 11th day, except for the normal group, the mice in the other groups were intraperitoneally injected with LPS (1 mg/kg), and the behavioral tests were performed 4 h later. Enzyme linked immunosorbent assay was used to detect tumor necrosis factor alpha (TNF- α) and interleukin-1 β (IL-1 β) levels in mice serum. The mRNA expression of indoleamine 2,3-dioxygenase (IDO) and nuclear transcription factor (NF- κB) were detected by real-time quantitative polymerase chain reaction. Western-blot analysis was used to detect IDO and NF- κB protein expressions in hippocampus tissue.

Results

Compared with the normal group, a single administration of LPS increased the immobility time in the forced swimming test (FST) and tail suspension test (TST, P<0.01), without affecting autonomous activity. Compared with the model group, fluoxetine and geniposide + eleutheroside B administration significantly improved the immobility time of depressed mice in the FST and TST, decreased serum IL-1 β content, inhibited the expression levels of NF- κ B gene and protein in hippocampus tissues (P<0.05 or P<0.01). Compared with the model group, geniposide + eleutheroside B treatment significantly reduced serum TNF-α content and inhibited IDO mRNA and protein expressions in hippocampus (P<0.05 or P<0.01). In addition, NMDA partly prevented the inhibition of IDO mRNA expression by geniposide + eleutheroside B; NMDA and WAY-100635 also partly prevented the reduction of IL-1 ß content induced by geniposide + eleutheroside B treatment (P<0.05 or P<0.01).

Conclusions

The combination of geniposide and eleutheroside B showed a certain antidepression-like effect. Its main mechanism of action may be contributed to inhibiting the activation of NF- κB, decreasing the proinflammatory cytokines such as TNF-α, IL-1 β, and inhibiting in the neuroinflammatory reaction. Additionally, it also affects tryptophan metabolism, reduces the expression of a key enzyme of tryptophan metabolism, IDO. And this antidepressant-like effect may be mediated by 5-hydroxytryptamine and glutamate systems.

Keywords

geniposide eleutheroside B antidepressant effect mechanism 5-hydroxytryptamine glutamate 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Author Contributions

Xu XQ, Chang HS, Zhang B contributed to the conception and study design. Zhang B contributed to the writing of this article. Zhang B, Chang HS, Hu KL, Yu X and Li LN contributed to conducting the study. All authors read and approved the manuscript for publication.

Conflict of Interest

The authors claim that there is no potential conflict of interest.

References

  1. 1.
    Baldessarini RJ. The basis for amine hypotheses in affective disorders: a critical evaluation. Arch Gen Psychiatry 1975;32:1087–1093.CrossRefGoogle Scholar
  2. 2.
    Correll CU, Detraux J, De LJ, De HM. Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry 2015;14:119–136.CrossRefGoogle Scholar
  3. 3.
    Stetler C, Miller GE. Depression and hypothalamic-pituitaryadrenal activation: a quantitative summary of four decades of research. Psychosom Med 2011;73:114.CrossRefGoogle Scholar
  4. 4.
    Leonard BE. Inflammation and depression: a causal or coincidental link to the pathophysiology? Acta Neuropsychiatr 2017;30:1.CrossRefGoogle Scholar
  5. 5.
    Xu XQ, Zong CC. A theoretical study on the treatment of depression with the method of ‘Purging Heart fire and nourishing Kidney water’. Chin J Basic Med Tradit Chin Med (Chin) 2015;25:393–394.Google Scholar
  6. 6.
    Xu XQ. Therapeutic effect of Eleutheroside senticosus combined with Gardenia on elderly patients with depressive disorder J. Chin J Gerontol (Chin) 2012;32:5383–5384.Google Scholar
  7. 7.
    Wei XH, Cheng XM, Shen JS, Wang ZT. Antidepressant effect of Yueju-Wan ethanol extract and its fractions in mice models of despair. J Ethnopharmacol 2008;117:339–344.CrossRefGoogle Scholar
  8. 8.
    Yao AM, Ma FF, Zhang LL, Feng F. Effect of aqueous extract and fractions of Zhi-Zi-Hou-Po Decoction against depression in inescapable stressed mice: restoration of monoamine neurotransmitters in discrete brain regions. Pharm Biol 2013;51:213–220.CrossRefGoogle Scholar
  9. 9.
    Zhou L, Wang MN, Zhu X, Cheng H, Wang YX, Du F, et al. Active ingredients, pharmacological actions, and clinical applications of acanthopanax in the central nervous system. J Hunan Univ Chin Med (Chin) 2018;38:961–964.Google Scholar
  10. 10.
    Koo HJ, Song YS, Kim HJ, Lee YH, Hong SM, Kim SJ, et al. Antiinflammatory effects of genipin, an active principle of gardenia. Eur J Pharmacol 2004;495:201–208.CrossRefGoogle Scholar
  11. 11.
    Zhao C, Zhang H, Li H, Lv C, Liu X, Li Z, et al. Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice. Neuropharmacology 2017;116:18–29.CrossRefGoogle Scholar
  12. 12.
    Gong X, Zhang L, Jiang R, Wang CD, Yin XR, Wan JY. Hepatoprotective effects of syringin on fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide in mice. J Appl Toxicol 2014;34:265–271.CrossRefGoogle Scholar
  13. 13.
    Huang L, Zhao H, Huang B, Zheng C, Peng W, Qin L. Acanthopanax senticosus: review of botany, chemistry and pharmacology. Pharmazie 2011;66:83–97.PubMedGoogle Scholar
  14. 14.
    Zhang A, Liu Z, Sheng L, Wu H. Protective effects of syringin against lipopolysaccharide-induced acute lung injury in mice. J Surg Res 2017;209:252–257.CrossRefGoogle Scholar
  15. 15.
    Zhao Y, Li H, Fang F, Qin T, Xiao W, Wang Z, et al. Geniposide improves repeated restraint stress-induced depression-like behavior in mice by ameliorating neuronal apoptosis via regulating GLP-1R/AKT signaling pathway. Neurosci Lett 2018;676:19–26.CrossRefGoogle Scholar
  16. 16.
    Zhou Y, Cheng C, Baranenko D, Wang J, Li Y, Lu W. Effects of Acanthopanax senticosus on brain injury induced by simulated spatial radiation in mouse model based on pharmacokinetics and comparative proteomics. Int J Mol Sci 2018;19:159.CrossRefGoogle Scholar
  17. 17.
    Zhao X, Cao F, Liu Q, Li X, Xu G, Liu G, et al. Behavioral, inflammatory and neurochemical disturbances in LPS and UCMS-induced mice models of depression. Behav Brain Res 2017:S0166432816313250.Google Scholar
  18. 18.
    Zhang GX, Sun BH. Research on independent activity patterns of mice. Chin Pharmacol Bull 2002;18:464–465.Google Scholar
  19. 19.
    Porsolt RD. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacolodyn 1977;229:327.Google Scholar
  20. 20.
    Stem L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 1985;85:367.CrossRefGoogle Scholar
  21. 21.
    Alexander C, Rietschel ET. Invited review: bacterial lipopolysaccharides and innate immunity. J Endotoxin Res 2001;7:167–202.PubMedGoogle Scholar
  22. 22.
    Hosseinizare MS, Gu F, Abdulla A, Powell S, Ziburkus J. Effects of experimental traumatic brain injury and impaired glutamate transport on cortical spreading depression. Exp Neurol 2017;295.Google Scholar
  23. 23.
    Hamon M, Lanfumey L, El MS, Boni C, Miquel MC, Bolanos F, et al. The main features of central 5-HT1 receptors. Neuropsychopharmacol 1990;3:349.Google Scholar
  24. 24.
    Francesc A. Serotonin receptors involved in antidepressant effects. Pharmacol Therapeut 2013;137:119–131.CrossRefGoogle Scholar
  25. 25.
    Müller CP, Carey RJ, Huston JP, De Souza Silva MA. Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors. Prog Neurobiol 2007;81:133–178.CrossRefGoogle Scholar
  26. 26.
    Cheetham SC, Crompton MR, Katona CL, Horton RW. Brain 5-HT1 binding sites in depressed suicides. Psychopharmacology 1990;102:544.CrossRefGoogle Scholar
  27. 27.
    Choi D. Glutamate neurotoxicity and diseases of the nervous system. Neuron 1988;1:623–634.CrossRefGoogle Scholar
  28. 28.
    Gasic GP, Hollmann M. Molecular neurobiology of glutamate receptors. Annu Rev Physiol 1992;54:507.CrossRefGoogle Scholar
  29. 29.
    Esra Kü, Melek ZS, Mecit C, Okan KK, Cüneyt ÜM. Zafer G. The change in plasma GABA, glutamine and glutamate levels in fluoxetine- or S-citalopram-treated female patients with major depression. Eur J Clin Pharmacol 2009;65:571–577.CrossRefGoogle Scholar
  30. 30.
    Pochwat B, Paucha-Poniewiera A, Szewczyk B, Pilc A. Nowak G. NMDA antagonists under investigation for the treatment of major depressive disorder. Expert Opin Inv Drug 2014;23:1181–1192.CrossRefGoogle Scholar
  31. 31.
    Jacoby AS, Munkholm K, Vinberg M, Pedersen BK, Kessing L. Cytokines, brain-derived neurotrophic factor and C-reactive protein in bipolar I disorder — Results from a prospective study. J Affect Disorders 2016;197:167–174.CrossRefGoogle Scholar
  32. 32.
    Hoffmann A, Baltimore D. Circuitry of nuclear factor κ B signaling. Immunol Rev 2006;210:171–186.CrossRefGoogle Scholar
  33. 33.
    Li W, Katz BP, Spinola SM. Haemophilus ducreyi lipooligosaccharides induce expression of the immunosuppressive enzyme indoleamine 2, 3-dioxygenase via type I interferons and tumor necrosis factor alpha in human dendritic cells. Infect Immun 2011;79:3338–3347.CrossRefGoogle Scholar
  34. 34.
    Maes M, Mihaylova I, Ruyter MD, Kubera M, Bosmans EJNEL. The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression and other conditions characterized by tryptophan depletion induced by inflammation. Neuro Endocrinol Lett 2007;28:826–831.PubMedGoogle Scholar
  35. 35.
    Lovelace MD, Varney B, Sundaram G, Lennon MJ, Chai KL, Jacobs K, et al. Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases. Neuropharmacology 2017;112(Pt B):373–388.CrossRefGoogle Scholar

Copyright information

© The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Bo Zhang
    • 1
  • Hong-sheng Chang
    • 1
  • Kai-li Hu
    • 1
  • Xue Yu
    • 2
  • Li-na Li
    • 2
  • Xiang-qing Xu
    • 3
    Email author
  1. 1.School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijingChina
  2. 2.School of Basic Medicine ScienceBeijing University of Chinese MedicineBeijingChina
  3. 3.Experiment Center, Encephalopathy DepartmentAffiliated Hospital of Shandong University of Chinese MedicineJinanChina

Personalised recommendations