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Capillarisin Suppresses Lipopolysaccharide-Induced Inflammatory Mediators in BV2 Microglial Cells by Suppressing TLR4-Mediated NF-κB and MAPKs Signaling Pathway

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Abstract

Capillarisin, one of the major bioactive compounds derived from Artemisia capillaries Thunb, has been reported to have extensive pharmacological properties, such as ant-inflammatory and anti-nociceptive activities. However, the molecular mechanisms responsible for the anti-inflammatory activity of capillarisin have not been elucidated in microglia. In the present study, we investigated the anti-inflammatory effects and molecular mechanisms of capillarisin on LPS-stimulated BV2 microglial cells. The effects of capillarisin on inflammatory mediators TNF-α, IL-6, IL-1β, NO and PGE2 were detected. The effects of capillarisin on NF-κB and MAPK activation were detected by western blotting. The results showed that capillarisin suppressed LPS-induced TNF-α, IL-6, IL-1β, NO and PGE2 production in a dose-dependent manner. Capillarisin also inhibited LPS-induced TLR4 expression, NF-κB and MAPKs activation in BV2 microglia. In conclusion, capillarisin inhibited LPS-induced inflammation by blocking TLR4-mediated NF-κB and MAPKs activation in BV2 microglia.

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References

  1. Skaper SD, Facci L, Giusti P (2014) Neuroinflammation, microglia and mast cells in the Pathophysiology of neurocognitive disorders: a review. CNS Neurol Disord Drug Targets 13:1654–1666

    Article  PubMed  Google Scholar 

  2. Li R, Huang YG, Fang D, Le WD (2004) (-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. J Neurosci Res 78:723–731

    Article  CAS  PubMed  Google Scholar 

  3. McGeer PL, McGeer EG (2014) Targeting microglia for the treatment of Alzheimer’s disease. Expert Opin Ther Targets 19:497–506

    Article  PubMed  Google Scholar 

  4. Merighi S, Gessi S, Varani K, Fazzi D, Stefanelli A, Borea PA (2013) Morphine mediates a proinflammatory phenotype via mu-opioid receptor-PKCvarepsilon-Akt-ERK1/2 signaling pathway in activated microglial cells. Biochem Pharmacol 86:487–496

    Article  CAS  PubMed  Google Scholar 

  5. Dello Russo C, Lisi L, Tringali G, Navarra P (2009) Involvement of mTOR kinase in cytokine-dependent microglial activation and cell proliferation. Biochem Pharmacol 78:1242–1251

    Article  CAS  PubMed  Google Scholar 

  6. Kao TK, Ou YC, Raung SL, Lai CY, Liao SL, Chen CJ (2010) Inhibition of nitric oxide production by quercetin in endotoxin/cytokine-stimulated microglia. Life Sci 86:315–321

    Article  CAS  PubMed  Google Scholar 

  7. Sehgal N, Agarwal V, Valli RK, Joshi SD, Antonovic L, Strobel HW, Ravindranath V (2011) Cytochrome P4504f, a potential therapeutic target limiting neuroinflammation. Biochem Pharmacol 82:53–64

    Article  CAS  PubMed  Google Scholar 

  8. Ock J, Kim S, Yi KY, Kim NJ, Han HS, Cho JY, Suk K (2010) A novel anti-neuroinflammatory pyridylimidazole compound KR-31360. Biochem Pharmacol 79:596–609

    Article  CAS  PubMed  Google Scholar 

  9. Pan XD, Chen XC, Zhu YG, Zhang J, Huang TW, Chen LM, Ye QY, Huang HP (2008) Neuroprotective role of tripchlorolide on inflammatory neurotoxicity induced by lipopolysaccharide-activated microglia. Biochem Pharmacol 76:362–372

    Article  CAS  PubMed  Google Scholar 

  10. Dai XJ, Li N, Yu L, Chen ZY, Hua R, Qin X, Zhang YM (2015) Activation of BV2 microglia by lipopolysaccharide triggers an inflammatory reaction in PC12 cell apoptosis through a toll-like receptor 4-dependent pathway. Cell Stress Chaperones 20:321–331

    Article  CAS  PubMed  Google Scholar 

  11. Zhu X, Owen JS, Wilson MD, Li H, Griffiths GL, Thomas MJ, Hiltbold EM, Fessler MB, Parks JS (2010) Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol. J Lipid Res 51:3196–3206

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Berbee JF, Coomans CP, Westerterp M, Romijn JA, Havekes LM, Rensen PC (2010) Apolipoprotein CI enhances the biological response to LPS via the CD14/TLR4 pathway by LPS-binding elements in both its N- and C-terminal helix. J Lipid Res 51:1943–1952

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Abate W, Alghaithy AA, Parton J, Jones KP, Jackson SK (2010) Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains. J Lipid Res 51:334–344

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Khan S, Shehzad O, Chun J, Choi RJ, Park S, Islam MN, Choi JS, Kim YS (2014) Anti-hyperalgesic and anti-allodynic activities of capillarisin via suppression of inflammatory signaling in animal model. J Ethnopharmacol 152:478–486

    Article  CAS  PubMed  Google Scholar 

  15. Lee JH, Chiang SY, Nam D, Chung WS, Lee J, Na YS, Sethi G, Ahn KS (2014) Capillarisin inhibits constitutive and inducible STAT3 activation through induction of SHP-1 and SHP-2 tyrosine phosphatases. Cancer Lett 345:140–148

    Article  CAS  PubMed  Google Scholar 

  16. Han S, Lee JH, Kim C, Nam D, Chung WS, Lee SG, Ahn KS, Cho SK, Cho M, Ahn KS (2013) Capillarisin inhibits iNOS, COX-2 expression, and proinflammatory cytokines in LPS-induced RAW 264.7 macrophages via the suppression of ERK, JNK, and NF-kappaB activation. Immunopharmacol Immunotoxicol 35:34–42

    Article  CAS  PubMed  Google Scholar 

  17. Khan S, Choi RJ, Shehzad O, Kim HP, Islam MN, Choi JS, Kim YS (2013) Molecular mechanism of capillarisin-mediated inhibition of MyD88/TIRAP inflammatory signaling in in vitro and in vivo experimental models. J Ethnopharmacol 145:626–637

    Article  CAS  PubMed  Google Scholar 

  18. Zhang F, Wang H, Wu Q, Lu Y, Nie J, Xie X, Shi J (2013) Resveratrol protects cortical neurons against microglia-mediated neuroinflammation. Phytotherapy research : PTR 27:344–349

    Article  CAS  PubMed  Google Scholar 

  19. Jayasooriya RG, Lee KT, Kang CH, Dilshara MG, Lee HJ, Choi YH, Choi IW, Kim GY (2014) Isobutyrylshikonin inhibits lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in BV2 microglial cells by suppressing the PI3 K/Akt-mediated nuclear transcription factor-kappaB pathway. Nutr Res 34:1111–1119

    Article  CAS  PubMed  Google Scholar 

  20. Kawabe K, Takano K, Moriyama M, Nakamura Y (2014) lipopolysaccharide-stimulated transglutaminase 2 expression enhances endocytosis activity in the mouse microglial cell line BV-2. Neuroimmunomodulation. doi:10.1159/000365484

    PubMed  Google Scholar 

  21. Kang SY, Jung HW, Lee MY, Lee HW, Chae SW, Park YK (2014) Effect of the semen extract of Cuscuta chinensis on inflammatory responses in LPS-stimulated BV-2 microglia. Chin J Nat Med 12:573–581

    PubMed  Google Scholar 

  22. Chu CH, Chen SH, Wang Q, Langenbach R, Li H, Zeldin D, Chen SL, Wang S, Gao H, Lu RB, Hong JS (2014) PGE inhibits IL-10 production via EP2-mediated beta-arrestin signaling in neuroinflammatory condition. Mol Neurobiol. doi:10.1007/s12035-014-8889-0

    Google Scholar 

  23. Velagapudi R, Aderogba M, Olajide OA (2014) Tiliroside, a dietary glycosidic flavonoid, inhibits TRAF-6/NF-kappaB/p38-mediated neuroinflammation in activated BV2 microglia. Biochim Biophys Acta 1840:3311–3319

    Article  CAS  PubMed  Google Scholar 

  24. Yu SY, Zuo LJ, Wang F, Chen ZJ, Hu Y, Wang YJ, Wang XM, Zhang W (2014) Potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment: a cross-sectional study. BMC Neurol 14:113

    Article  PubMed Central  PubMed  Google Scholar 

  25. Pisanu A, Lecca D, Mulas G, Wardas J, Simbula G, Spiga S, Carta AR (2014) Dynamic changes in pro- and anti-inflammatory cytokines in microglia after PPAR-gamma agonist neuroprotective treatment in the MPTPp mouse model of progressive Parkinson’s disease. Neurobiol Dis 71:280–291

    Article  CAS  PubMed  Google Scholar 

  26. Yu H, Valerio M, Bielawski J (2013) Fenretinide inhibited de novo ceramide synthesis and proinflammatory cytokines induced by Aggregatibacter actinomycetemcomitans. J Lipid Res 54:189–201

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Cai L, Wang Z, Meyer JM, Ji A, van der Westhuyzen DR (2012) Macrophage SR-BI regulates LPS-induced pro-inflammatory signaling in mice and isolated macrophages. J Lipid Res 53:1472–1481

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Heyninck K, Lahtela-Kakkonen M, Van der Veken P, Haegeman G, Vanden Berghe W (2014) Withaferin A inhibits NF-kappaB activation by targeting cysteine 179 in IKKbeta. Biochem Pharmacol 91:501–509

    Article  CAS  PubMed  Google Scholar 

  29. Wang L, Xu Y, Yu Q, Sun Q, Xu Y, Gu Q, Xu X (2014) H-RN, a novel antiangiogenic peptide derived from hepatocyte growth factor inhibits inflammation in vitro and in vivo through PI3 K/AKT/IKK/NF-kappaB signal pathway. Biochem Pharmacol 89:255–265

    Article  CAS  PubMed  Google Scholar 

  30. Danai LV, Guilherme A, Guntur KV, Straubhaar J, Nicoloro SM, Czech MP (2013) Map4k4 suppresses Srebp-1 and adipocyte lipogenesis independent of JNK signaling. J Lipid Res 54:2697–2707

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This study was supported by grants from the Natural Science Foundation of Chongqing (Grant No. CSTC2012JJA10067).

Conflict of interest

All authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, The Second Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing, 400010, People’s Republic of China

    Zhen Yu, Lifen Chen, Jifang Li & Changlin Hu

  2. Department of Neurology, The Fifth Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing, 400010, People’s Republic of China

    Ling Tang

  3. Department of Neurology, The First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing, 400010, People’s Republic of China

    Wanfu Wu

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  1. Zhen Yu
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  2. Ling Tang
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Correspondence to Zhen Yu.

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Yu, Z., Tang, L., Chen, L. et al. Capillarisin Suppresses Lipopolysaccharide-Induced Inflammatory Mediators in BV2 Microglial Cells by Suppressing TLR4-Mediated NF-κB and MAPKs Signaling Pathway. Neurochem Res 40, 1095–1101 (2015). https://doi.org/10.1007/s11064-015-1567-4

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  • DOI: https://doi.org/10.1007/s11064-015-1567-4

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