Skip to main content

Advertisement

SpringerLink
Log in

Extract of Fructus Schisandrae chinensis Inhibits Neuroinflammation Mediator Production from Microglia via NF-κ B and MAPK Pathways

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate the anti-neuroinflammation effect of extract of Fructus Schisandrae chinensis (EFSC) on lipopolysaccharide (LPS)-induced BV-2 cells and the possible involved mechanisms.

Methods

Primary cortical neurons were isolated from embryonic (E17-18) cortices of Institute of Cancer Research (ICR) mouse fetuses. Primary microglia and astroglia were isolated from the frontal cortices of newborn ICR mouse. Different cells were cultured in specific culture medium. Cells were divided into 5 groups: control group, LPS group (treated with 1 μg/mL LPS only) and EFSC groups (treated with 1 μg/mL LPS and 100, 200 or 400 mg/mL EFSC, respectively). The effect of EFSC on cells viability was tested by methylthiazolyldiphenyltetrazolium bromide (MTT) colorimetric assay. EFSC-mediated inhibition of LPS-induced production of pro-inflammatory mediators, such as nitrite oxide (NO) and interleukin-6 (IL-6) were quantified and neuron-protection effect against microglia-mediated inflammation injury was tested by hoechst 33258 apoptosis assay and crystal violet staining assay. The expression of pro-inflammatory marker proteins was evaluated by Western blot analysis or immunofluorescence.

Results

EFSC (200 and 400 mg/mL) reduced NO, IL-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression in LPS-induced BV-2 cells (P<0.01 or P<0.05). EFSC (200 and 400 mg/mL) reduced the expression of NO in LPS-induced primary microglia and astroglia (P<0.01). In addition, EFSC alleviated cell apoptosis and inflammation injury in neurons exposed to microglia-conditioned medium (P<0.01). The mechanistic studies indicated EFSC could suppress nuclear factor (NF)-?B phosphorylation and its nuclear translocation (P<0.01). The anti-inflammatory effect of EFSC occurred through suppressed activation of mitogen-activated protein kinase (MAPK) pathway (P<0.01 or P<0.05).

Conclusion

EFSC acted as an anti-inflammatory agent in LPS-induced glia cells. These effects might be realized through blocking of NF-κB activity and inhibition of MAPK signaling pathways.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. McNaull BB, Todd S, McGuinness B, Passmore AP. Passmore Inflammation and anti–inflammatory strategies for Alzheimer’s disease–a mini–review. Gerontology 2010;56:3–14.

    Article  CAS  PubMed  Google Scholar 

  2. Suzuki T, Hide I, Matsubara A, Hama C, Harada K, Miyano K, et al. Nakata microglial alpha7 nicotinic acetylcholine receptors drive a phospholipase C/IP3 pathway and modulate the cell activation toward a neuroprotective role. J Neurosci Res 2006;83:1461–1470.

    Article  CAS  PubMed  Google Scholar 

  3. Birch AM. The contribution of astrocytes to Alzheimer’s disease. Biochem Soc Trans 2014;42:1316–1320.

    Article  CAS  PubMed  Google Scholar 

  4. Phillips EC, Croft CL, Kurbatskaya K, O’Neill MJ, Hutton ML, Hanger DP. Astrocytes and neuroinflammation in Alzheimer’s disease? Biochem Soc Trans 2014;42:1321–1325.

    Article  CAS  PubMed  Google Scholar 

  5. Lawrence T, Fong C. The resolution of inflammation: antiinflammatory roles for NF–kappaB. Int J Biochem Cell Biol 2010;42:519–523.

    Article  CAS  PubMed  Google Scholar 

  6. Albensi BC, Mattson MP. Evidence for the involvement of TNF and NF–kappaB in hippocampal synaptic plasticity. Synapse 2000;35:151–159.

    Article  CAS  PubMed  Google Scholar 

  7. Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D. NF–kappaB functions in synaptic signaling and behavior. Nat Neurosci 2003;6:1072–1078.

    Article  CAS  PubMed  Google Scholar 

  8. Levenson JM, Choi S, Lee SY, Cao YA, Ahn HJ, Worley KC, et al. A bioinformatics analysis of memory consolidation reveals involvement of the transcription factor c–rel. J Neurosci 2004;24:3933–3943.

    Article  CAS  PubMed  Google Scholar 

  9. Freudenthal R, Locatelli F, Hermitte G, Maldonado H, Lafourcade C, Delorenzi A, et al. Kappa–B like DNA–binding activity is enhanced after spaced training that induces longterm memory in the crab Chasmagnathus. Neurosci Lett 1998;242:143–146.

    Article  CAS  PubMed  Google Scholar 

  10. Merlo E, Freudenthal R, Romano A. The IkappaB kinase inhibitor sulfasalazine impairs long–term memory in the crab Chasmagnathus. Neuroscience 2002;112:161–172.

    Article  CAS  PubMed  Google Scholar 

  11. Gaestel M, Mengel A, Bothe U, Asadullah K. Protein kinases as small molecule inhibitor targets in inflammation. Curr Med Chem 2007;14:2214–2234.

    Article  CAS  PubMed  Google Scholar 

  12. Torres M, Forman HJ. Redox signaling and the MAP kinase pathways. Biofactors 2003; 17:287–296.

    Article  CAS  PubMed  Google Scholar 

  13. Song F, Zeng K, Liao L, Yu Q, Tu P, Wang X. Schizandrin A inhibits microglia–mediated neuroninflammation through inhibiting TRAF6–NF–κB and Jak2–Stat3 signaling pathways. PLoS One 2016;11:e0149991.

    Google Scholar 

  14. Zeng KW, Zhang T, Fu H, Liu GX, Wang XM. Schisandrin B exerts anti–neuroinflammatory activity by inhibiting the Toll–like receptor 4–dependent MyD88/IKK/NF–κB signaling pathway in lipopolysaccharide–induced microglia. Eur J Pharmacol 2012;692:29–37.

    Article  CAS  PubMed  Google Scholar 

  15. Kang YS, Han MH, Hong SH, Park C, Hwang HJ, Kim BW, et al. Anti–inflammatory effects of Schisandra chinensis (Turcz.) baill fruit through the inactivation of nuclear factor–κB and mitogen–activated protein kinases signaling pathways in lipopolysaccharide–stimulated murine macrophages. J Cancer Prev 2014;19:279–287.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fellner L, Irschick R, Schanda K, Reindl M, Klimaschewski L, Poewe W, et al. Toll–like receptor 4 is required for α–synuclein dependent activation of microglia and astroglia. Glia 2013;61:349–360.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Izant JG, McIntosh JR. Microtubule–associated proteins: a monoclonal antibody to MAP2 binds to differentiated neurons. Proc Natl Acad Sci USA 1980;77:4741–4745.

    Article  CAS  PubMed  Google Scholar 

  18. Tsikas D. Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: appraisal of the Griess reaction in the L–arginine/nitric oxide area of research. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 851:51–70.

    Article  CAS  PubMed  Google Scholar 

  19. Dong W, Yu S, Deng Y, Pan T. Screening of lignan patterns in Schisandra species using ultrasonic assisted temperature switch ionic liquid microextraction followed by UPLC–MS/MS analysis. J Chromatogr B Analyt Technol Biomed Life Sci 2016;1008:45–49.

    Article  CAS  PubMed  Google Scholar 

  20. Wei B, Li Q, Su D, Fan R, Zhao L, Geng L, et al. Development of a UFLC–MS/MS method for simultaneous determination of six lignans of Schisandra chinensis (Turcz.) Baill. in rat plasma and its application to a comparative pharmacokinetic study in normal and insomnic rats. J Pharm Biomed Anal 2013;77:120–127.

    Article  CAS  PubMed  Google Scholar 

  21. Sharma JN, Al–Omran A, Parvathy SS. Role of nitric oxide in inflammatory diseases. Inflammopharmacology 2007;15:252–259.

    Article  CAS  PubMed  Google Scholar 

  22. Boscá L, Zeini M, Través PG, Hortelano S. Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate. Toxicology 2005;208:249–258.

    Article  CAS  PubMed  Google Scholar 

  23. Murakami A, Ohigashi H. Targeting NOX, INOS and COX–2 in inflammatory cells: chemoprevention using food phytochemicals. Int J Cancer 2007;121:2357–2363.

    Article  CAS  PubMed  Google Scholar 

  24. Pimplikar SW. Neuroinflammation in Alzheimer’s disease: from pathogenesis to a therapeutic target. J Clin Immunol 2014;34 (Suppl 1):S64–S69.

    Google Scholar 

  25. Jacobs MD, Harrison SC. Structure of an IkappaBalpha/NFkappaB complex. Cell 1998;95:749–758.

    Article  CAS  PubMed  Google Scholar 

  26. Gilroy DW, Lawrence T, Perretti M, Rossi AG. Inflammatory resolution resolution: new opportunities for drug discovery. Nat Rev Drug Discov 2004;3:401–416.

    Article  CAS  PubMed  Google Scholar 

  27. Lawrence T, Fong C. The resolution of inflammation: antiinflammatory roles for NF–kappaB. Int J Biochem Cell Biol 2010;42:519–523.

    Article  CAS  PubMed  Google Scholar 

  28. Gaestel M, Mengel A, Bothe U, Asadullah K. Protein kinases as small molecule inhibitor targets in inflammation. Curr Med Chem 2007;14:2214–2234.

    Article  CAS  PubMed  Google Scholar 

  29. Torres M, Forman HJ. Redox signaling and the MAP kinase pathways. Biofactors 2003;17:287–296.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Studio of Integration of Traditional and Western Medicine, First Hospital, Peking University, Beijing, 100034, China

    Fang-jiao Song, Yuan Li & Xue-mei Wang

  2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China

    Ke-wu Zeng, Jin-feng Chen, Xiao-min Song & Peng-fei Tu

Authors
  1. Fang-jiao Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ke-wu Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jin-feng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao-min Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peng-fei Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xue-mei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xue-mei Wang.

Additional information

Supported by the National Natural Science Foundation of China (No.81173369, 81303253 and 81530099), the Natural Science Foundation of Beijing (No. 7132210), the Doctoral Scientific Fund Project of the Ministry of Education of China (No. 20120001110105)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, Fj., Zeng, Kw., Chen, Jf. et al. Extract of Fructus Schisandrae chinensis Inhibits Neuroinflammation Mediator Production from Microglia via NF-κ B and MAPK Pathways. Chin. J. Integr. Med. 25, 131–138 (2019). https://doi.org/10.1007/s11655-018-3001-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-018-3001-7

Keywords

Search

Navigation