[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content

Advertisement

Springer Nature Link
Log in

Hesperidin Alleviates Lipopolysaccharide-Induced Neuroinflammation in Mice by Promoting the miRNA-132 Pathway

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Previous studies have demonstrated that hesperidin, a flavanone glycoside from citrus fruits, produces antidepressant-like effects in both mice and rats. However, whether these effects are mediated by pro-inflammatory cytokines remains unknown. In the present study, we attempted to investigate the effects of hesperidin on the depressive-like behavior; the serum corticosterone concentrations; and the interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) levels in lipopolysaccharide (LPS)-induced depression-like mice. In particular, we evaluated the miRNA-132 expression after LPS and hesperidin treatment. We found that LPS injection not only decreased the sucrose preference and increased the serum corticosterone levels but also elevated IL-1β, IL-6, and TNF-α in the prefrontal cortex. More importantly, LPS down-regulated the expression of miRNA-132. Pre-treatment with hesperidin (25, 50, 100 mg/kg) for 7 days prevented these abnormalities induced by LPS injection. In contrast, this effect of hesperidin was abolished by a miRNA-132 antagomir. Taken together, these results suggest that the antidepressant-like mechanisms of hesperidin are at least partially related to decreased pro-inflammatory cytokine levels via the miRNA-132 pathway in the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Howren, M.B., D.M. Lamkin, and J. Suls. 2009. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic Medicine 71: 171–186.

    Article  CAS  PubMed  Google Scholar 

  2. Al-Hakeim, H.K., D.A. Al-Rammahi, and A.H. Al-Dujaili. 2015. IL-6, IL-18, sIL-2R, and TNFalpha proinflammatory markers in depression and schizophrenia patients who are free of overt inflammation. Journal of Affective Disorders 182: 106–114.

    Article  CAS  PubMed  Google Scholar 

  3. Gupta, R., K. Gupta, A.K. Tripathi, M.S. Bhatia, and L.K. Gupta. 2016. Effect of mirtazapine treatment on serum levels of brain-derived neurotrophic factor and tumor necrosis factor-alpha in patients of major depressive disorder with severe depression. Pharmacology 97: 184–188.

    Article  CAS  PubMed  Google Scholar 

  4. Hashimoto, T., et al. 2015. Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study. Neuropsychiatric Disease and Treatment 11: 3031–3040.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Li, R., D. Zhao, R. Qu, Q. Fu, and S. Ma. 2015. The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice. Neuroscience Letters 594: 17–22.

    Article  CAS  PubMed  Google Scholar 

  6. Ge, L., L. Liu, H. Liu, S. Liu, H. Xue, X. Wang, L. Yuan, Z. Wang, and D. Liu. 2015. Resveratrol abrogates lipopolysaccharide-induced depressive-like behavior, neuroinflammatory response, and CREB/BDNF signaling in mice. European Journal of Pharmacology 768: 49–57.

    Article  CAS  PubMed  Google Scholar 

  7. Shaked, I., A. Meerson, Y. Wolf, R. Avni, D. Greenberg, A. Gilboa-Geffen, and H. Soreq. 2009. MicroRNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase. Immunity 31: 965–973.

    Article  CAS  PubMed  Google Scholar 

  8. Yi, L.T., J. Li, B.B. Liu, L. Luo, Q. Liu, and D. Geng. 2014. BDNF-ERK-CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice. Journal of Psychiatry & Neuroscience 39: 348–359.

    Article  Google Scholar 

  9. Chang, C.Y., T.Y. Lin, C.W. Lu, S.K. Huang, Y.C. Wang, S.S. Chou, and S.J. Wang. 2015. Hesperidin inhibits glutamate release and exerts neuroprotection against excitotoxicity induced by kainic acid in the hippocampus of rats. Neurotoxicology 50: 157–169.

    Article  CAS  PubMed  Google Scholar 

  10. Justin Thenmozhi, A., T.R. Raja, U. Janakiraman, and T. Manivasagam. 2015. Neuroprotective effect of hesperidin on aluminium chloride induced Alzheimer’s disease in Wistar rats. Neurochemical Research 40: 767–776.

    Article  PubMed  Google Scholar 

  11. Antunes, M.S., A.T. Goes, S.P. Boeira, M. Prigol, and C.R. Jesse. 2014. Protective effect of hesperidin in a model of Parkinson’s disease induced by 6-hydroxydopamine in aged mice. Nutrition 30: 1415–1422.

    Article  CAS  PubMed  Google Scholar 

  12. Oztanir, M.N., O. Ciftci, A. Cetin, and M.A. Aladag. 2014. Hesperidin attenuates oxidative and neuronal damage caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model. Neurological Sciences 35: 1393–1399.

    Article  PubMed  Google Scholar 

  13. Souza, L.C., M.G. de Gomes, A.T. Goes, L. Del Fabbro, C.B. Filho, S.P. Boeira, and C.R. Jesse. 2013. Evidence for the involvement of the serotonergic 5-HT(1A) receptors in the antidepressant-like effect caused by hesperidin in mice. Progress in Neuro-Psychopharmacology & Biological Psychiatry 40: 103–109.

    Article  CAS  Google Scholar 

  14. Filho, C.B., L. Del Fabbro, M.G. de Gomes, A.T. Goes, L.C. Souza, S.P. Boeira, and C.R. Jesse. 2013. Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test. European Journal of Pharmacology 698: 286–291.

    Article  CAS  PubMed  Google Scholar 

  15. Donato, F., M.G. de Gomes, A.T. Goes, C.B. Filho, L. Del Fabbro, M.S. Antunes, L.C. Souza, S.P. Boeira, and C.R. Jesse. 2014. Hesperidin exerts antidepressant-like effects in acute and chronic treatments in mice: possible role of l-arginine-NO-cGMP pathway and BDNF levels. Brain Research Bulletin 104: 19–26.

    Article  CAS  PubMed  Google Scholar 

  16. Donato, F., et al. 2015. Evidence for the involvement of potassium channel inhibition in the antidepressant-like effects of hesperidin in the tail suspension test in mice. Journal of Medicinal Food 18: 818–823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. El-Marasy, S.A., H.M. Abdallah, S.M. El-Shenawy, A.S. El-Khatib, O.A. El-Shabrawy, and S.A. Kenawy. 2014. Anti-depressant effect of hesperidin in diabetic rats. Canadian Journal of Physiology and Pharmacology 92: 945–952.

    Article  CAS  PubMed  Google Scholar 

  18. Liu, X.X., et al. 2015. Hesperidin ameliorates lipopolysaccharide-induced acute lung injury in mice by inhibiting HMGB1 release. International Immunopharmacology 25: 370–376.

    Article  CAS  PubMed  Google Scholar 

  19. Kaur, G., N. Tirkey, and K. Chopra. 2006. Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity. Toxicology 226: 152–160.

    Article  CAS  PubMed  Google Scholar 

  20. Ho, S.C., and C.T. Kuo. 2014. Hesperidin, nobiletin, and tangeretin are collectively responsible for the anti-neuroinflammatory capacity of tangerine peel (Citri reticulatae pericarpium). Food and Chemical Toxicology 71: 176–182.

    Article  CAS  PubMed  Google Scholar 

  21. Li, C., C. Zug, H. Qu, H. Schluesener, and Z. Zhang. 2015. Hesperidin ameliorates behavioral impairments and neuropathology of transgenic APP/PS1 mice. Behavioural Brain Research 281: 32–42.

    Article  CAS  PubMed  Google Scholar 

  22. O'Connor, J.C., Lawson, M.A., André, C., Moreau, M., Lestage, J., Castanon, N., Kelley, K.W., Dantzer, R. 2009. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Molecular Psychiatry. 14: 511–522.

  23. Porsolt, R.D., A. Bertin, and M. Jalfre. 1977. Behavioral despair in mice: a primary screening test for antidepressants. Archives Internationales de Pharmacodynamie et de Thérapie 229: 327–336.

    CAS  PubMed  Google Scholar 

  24. Dantzer, R., J.C. O’Connor, G.G. Freund, R.W. Johnson, and K.W. Kelley. 2008. From inflammation to sickness and depression: when the immune system subjugates the brain. Nature Reviews Neuroscience 9: 46–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cai, L., R. Li, Q.Q. Wu, and T.N. Wu. 2013. [Effect of hesperidin on behavior and HPA axis of rat model of chronic stress-induced depression]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 38: 229–233.

    PubMed  Google Scholar 

  26. Hernandez, M.E., D. Mendieta, M. Perez-Tapia, R. Bojalil, I. Estrada-Garcia, S. Estrada-Parra, and L. Pavon. 2013. Effect of selective serotonin reuptake inhibitors and immunomodulator on cytokines levels: an alternative therapy for patients with major depressive disorder. Clinical & Developmental Immunology 2013: 267871.

    Article  Google Scholar 

  27. Silverman, M.N., and E.M. Sternberg. 2012. Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. Annals of the New York Academy of Sciences 1261: 55–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Walker, A.K., D.P. Budac, S. Bisulco, A.W. Lee, R.A. Smith, B. Beenders, K.W. Kelley, and R. Dantzer. 2013. NMDA receptor blockade by ketamine abrogates lipopolysaccharide-induced depressive-like behavior in C57BL/6 J mice. Neuropsychopharmacology 38: 1609–1616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhao, Y., Y. Zhang, and F. Pan. 2015. The effects of EGb761 on lipopolysaccharide-induced depressive-like behaviour in C57BL/6 J mice. Central-European journal of immunology 40: 11–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Dantzer, R., J.C. O’Connor, M.A. Lawson, and K.W. Kelley. 2011. Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology 36: 426–436.

    Article  CAS  PubMed  Google Scholar 

  31. Wang, N., H.Y. Yu, X.F. Shen, Z.Q. Gao, C. Yang, J.J. Yang, and G.F. Zhang. 2015. The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus. Upsala Journal of Medical Sciences 120: 241–248.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Du, R.W., R.H. Du, and W.G. Bu. 2014. beta-Arrestin 2 mediates the anti-inflammatory effects of fluoxetine in lipopolysaccharide-stimulated microglial cells. Journal of Neuroimmune Pharmacology 9: 582–590.

    Article  PubMed  Google Scholar 

  33. Hansen, K.F., K. Karelina, K. Sakamoto, G.A. Wayman, S. Impey, and K. Obrietan. 2013. miRNA-132: a dynamic regulator of cognitive capacity. Brain Structure & Function 218: 817–831.

    Article  Google Scholar 

  34. Marler, K.J., et al. 2014. BDNF promotes axon branching of retinal ganglion cells via miRNA-132 and p250GAP. The Journal of Neuroscience 34: 969–979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Marques-Rocha, J.L., M. Samblas, F.I. Milagro, J. Bressan, J.A. Martinez, and A. Marti. 2015. Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB Journal 29: 3595–3611.

    Article  CAS  PubMed  Google Scholar 

  36. Pan, B., and Y. Liu. 2015. Effects of duloxetine on microRNA expression profile in frontal lobe and hippocampus in a mouse model of depression. International Journal of Clinical and Experimental Pathology 8: 15454–15461.

    PubMed  PubMed Central  Google Scholar 

  37. Fan, G., X. Jiang, X. Wu, P.A. Fordjour, L. Miao, H. Zhang, Y. Zhu, and X. Gao. 2016. Anti-inflammatory activity of Tanshinone IIA in LPS-stimulated RAW264.7 macrophages via miRNAs and TLR4-NF-kappaB pathway. Inflammation 39: 375–384.

    Article  CAS  PubMed  Google Scholar 

  38. Fen, L., J. Rong, Z. Zhenguo, Z. Ning, X. Liang, N. Cheng, and Q. Kejian. 2014. The expression changes in microRNA-132 in the lipopolysaccharide-induced inflammation of rat alveolar macrophages. Zhonghua wei zhong bing ji jiu yi xue 26: 80–83.

    PubMed  Google Scholar 

  39. Liu, F., et al. 2015. miR-132 inhibits lipopolysaccharide-induced inflammation in alveolar macrophages by the cholinergic anti-inflammatory pathway. Experimental Lung Research 41: 261–269.

    Article  PubMed  Google Scholar 

  40. Kong, H., F. Yin, F. He, A. Omran, L. Li, T. Wu, Y. Wang, and J. Peng. 2015. The Effect of miR-132, miR-146a, and miR-155 on MRP8/TLR4-induced astrocyte-related inflammation. Journal of Molecular Neuroscience 57: 28–37.

    Article  CAS  PubMed  Google Scholar 

Download references

Authors’ Contributions

Min Li and Bingyu Qin designed the study and wrote the protocol. Min Li and Huanzhang Shao performed the experiments. Min Li and Xia Zhang took part in the data analysis. Min Li and Bingyu Qin wrote the first version of the manuscript, and all authors approved the article for submission.

Author information

Authors and Affiliations

  1. Central ICU, Henan Province People’s Hospital, Zhengzhou, 450003, Henan Province, PR China

    Min Li, Huanzhang Shao, Xia Zhang & Bingyu Qin

Authors
  1. Min Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huanzhang Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xia Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bingyu Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bingyu Qin.

Ethics declarations

Animal experiments were approved by Henan Province People’s Hospital’s Animal Committee and were conducted in accordance with the Committee’s guidelines, which comply with all applicable international and national guidelines for the care and use of animals.

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, M., Shao, H., Zhang, X. et al. Hesperidin Alleviates Lipopolysaccharide-Induced Neuroinflammation in Mice by Promoting the miRNA-132 Pathway. Inflammation 39, 1681–1689 (2016). https://doi.org/10.1007/s10753-016-0402-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-016-0402-7

KEY WORDS

Search

Navigation