Skip to main content

Advertisement

SpringerLink
Log in

Acacetin Attenuates Neuroinflammation via Regulation the Response to LPS Stimuli In Vitro and In Vivo

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Under normal conditions in the brain, microglia play roles in homeostasis regulation and defense against injury. However, over-activated microglia secrete proinflammatory and cytotoxic factors that can induce progressive brain disorders, including Alzheimer’s disease, Parkinson’s disease and ischemia. Therefore, regulation of microglial activation contributes to the suppression of neuronal diseases via neuroinflammatory regulation. In this study, we investigated the effects of acacetin (5,7-dihydroxy-4′-methoxyflavone), which is derived from Robinia pseudoacacia, on neuroinflammation in lipopolysaccharide (LPS)-stimulated BV-2 cells and in animal models of neuroinflammation and ischemia. Acacetin significantly inhibited the release of nitric oxide (NO) and prostaglandin E2 and the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated BV-2 cells. The compound also reduced proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β, and inhibited the activation of nuclear factor-κB and p38 mitogen-activated protein kinase. In an LPS-induced neuroinflammation mouse model, acacetin significantly suppressed microglial activation. Moreover, acacetin reduced neuronal cell death in an animal model of ischemia. These results suggest that acacetin may act as a potential therapeutic agent for brain diseases involving neuroinflammation.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ha SK, Lee P, Park JA, Oh HR, Lee SY, Park JH, Lee EH, Ryu JH, Lee KR, Kim SY (2008) Apigenin inhibits the production of NO and PGE2 in microglia and inhibits neuronal cell death in a middle cerebral artery occlusion-induced focal ischemia mice model. Neurochem Int 52(4–5):878–886

    Article  PubMed  CAS  Google Scholar 

  2. Ha SK, Moon E, Kim SY (2010) Chrysin suppresses LPS-stimulated proinflammatory responses by blocking NF-κB and JNK activations in microglia cells. Neurosci Lett 485(3):143–147

    Article  PubMed  CAS  Google Scholar 

  3. Lee H, Kim YO, Kim H, Kim SY, Noh HS, Kang SS, Cho GJ, Choi WS, Suk K (2003) Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. FASEB J 17(13):1943–1944

    PubMed  CAS  Google Scholar 

  4. Cody V (1988) Crystal and molecular structures of flavonoids. Prog Clin Biol Res 280:29–44

    PubMed  CAS  Google Scholar 

  5. Pan MH, Lai CS, Wang YJ, Ho CT (2006) Acacetin suppressed LPS-induced up-expression of iNOS and COX-2 in murine macrophages and TPA-induced tumor promotion in mice. Biochem Pharmacol 72(10):1293–1303

    Article  PubMed  CAS  Google Scholar 

  6. Liao YH, Houghton PJ, Hoult JR (1999) Novel and known constituents from Buddleja species and their activity against leukocyte eicosanoid generation. J Nat Prod 62(9):1241–1245

    Article  PubMed  CAS  Google Scholar 

  7. Kraft C, Jenett-Siems K, Siems K, Jakupovic J, Mavi S, Bienzle U, Eich E (2003) In vitro antiplasmodial evaluation of medicinal plants from Zimbabwe. Phytother Res 17(2):123–128

    Article  PubMed  CAS  Google Scholar 

  8. Singh RP, Agrawal P, Yim D, Agarwal C, Agarwal R (2005) Acacetin inhibits cell growth and cell cycle progression, and induces apoptosis in human prostate cancer cells: structure-activity relationship with linarin and linarin acetate. Carcinogenesis 26(4):845–854

    Article  PubMed  CAS  Google Scholar 

  9. Block ML, Hong JS (2005) Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76(2):77–98

    Article  PubMed  CAS  Google Scholar 

  10. Perry VH, Gordon S (1988) Macrophages and microglia in the nervous system. Trends Neurosci 11(6):273–277

    Article  PubMed  CAS  Google Scholar 

  11. Hanisch UK (2002) Microglia as a source and target of cytokines. Glia 40(2):140–155

    Article  PubMed  Google Scholar 

  12. Minghetti L, Levi G (1998) Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog Neurobiol 54(1):99–125

    Article  PubMed  CAS  Google Scholar 

  13. Gonzalez-Scarano F, Baltuch G (1999) Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 22:219–240

    Article  PubMed  CAS  Google Scholar 

  14. Tak PP, Firestein GS (2001) NF-κB: a key role in inflammatory diseases. J Clin Invest 107(1):7–11

    Article  PubMed  CAS  Google Scholar 

  15. Schieven GL (2005) The biology of p38 kinase: a central role in inflammation. Curr Top Med Chem 5(10):921–928

    Article  PubMed  CAS  Google Scholar 

  16. Waetzig V, Czeloth K, Hidding U, Mielke K, Kanzow M, Brecht S, Goetz M, Lucius R, Herdegen T, Hanisch UK (2005) c-Jun N-terminal kinases (JNKs) mediate pro-inflammatory actions of microglia. Glia 50(3):235–246

    Article  PubMed  Google Scholar 

  17. Park JS, Woo MS, Kim SY, Kim WK, Kim HS (2005) Repression of interferon-gamma-induced inducible nitric oxide synthase (iNOS) gene expression in microglia by sodium butyrate is mediated through specific inhibition of ERK signaling pathways. J Neuroimmunol 168(1–2):56–64

    Article  PubMed  CAS  Google Scholar 

  18. Blasi E, Barluzzi R, Bocchini V, Mozzolla R, Bistoni F (1990) Immortalization of murine microglial cells by a v-raf/v-myc carrying carrying retrovirus. J Neuroimmunol 27(2–3):229–237

    Article  PubMed  CAS  Google Scholar 

  19. Cho KO, Kim SK, Cho YJ, Sung KW, Kim SY (2007) Regional differences in the neuroprotective effect of minocycline in a mouse model of global forebrain ischemia. Life Sci 80(22):2030–2035

    Article  PubMed  CAS  Google Scholar 

  20. Fernandez AP, Pozo-Rodrigalvarez A, Serrano J, Martinez-Murillo R (2010) Nitric oxide: target for therapeutic strategies in Alzheimer’s disease. Curr Pharm Des 16(25):2837–2850

    PubMed  CAS  Google Scholar 

  21. Aquilano K, Baldelli S, Rotilio G, Ciriolo MR (2008) Role of nitric oxide synthases in Parkinson’s disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem Res 33(12):2416–2426

    Article  PubMed  CAS  Google Scholar 

  22. Parmentier S, Bohme GA, Lerouet D, Damour D, Stutzmann JM, Margaill I, Plotkine M (1999) Selective inhibition of inducible nitric oxide synthase prevents ischaemic brain injury. Br J Pharmacol 127(2):546–552

    Article  PubMed  CAS  Google Scholar 

  23. Giovannini MG, Scali C, Prosperi C, Bellucci A, Pepeu G, Casamenti F (2003) Experimental brain inflammation and neurodegeneration as model of Alzheimer’s disease: protective effects of selective COX-2 inhibitors. Int J Immunopathol Pharmacol 16(2 Suppl):31–40

    PubMed  CAS  Google Scholar 

  24. Barone FC, Feuerstein GZ (1999) Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19(8):819–834

    Article  PubMed  CAS  Google Scholar 

  25. Samson Y, Lapergue B, Hosseini H (2005) Inflammation and ischaemic stroke: current status and future perspectives. Rev Neurol (Paris) 161(12 Pt 1):1177–1182

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Kyung Hee University Post-Doctoral Fellowship program in 2009 (KHU-20090448).

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Graduate School of East–West Medical Science, East–West Integrated Medical Science Research Center, Kyung Hee University Global Campus, #1732 Deogyeong-daero, Giheung-gu, Yongin, Gyeonggi-do, 446-701, Republic of Korea

    Sang Keun Ha, Eunjung Moon & Sun Yeou Kim

  2. Korea Food Research Institute, #516 Baekhyun-dong, Bundang-gu, Sungnam, Gyeonggi-do, 463-746, Republic of Korea

    Sang Keun Ha

  3. Department of Natural Medicine Resources, Semyung University, #21 Sinwoul-dong, Jecheon, Chungcheongbuk-do, 390-711, Republic of Korea

    Pyeongjae Lee

  4. Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East–West Pharmaceutical Research Institute, Kyung Hee University Seoul Campus, #1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea

    Jong Hoon Ryu & Myung Sook Oh

Authors
  1. Sang Keun Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eunjung Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pyeongjae Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jong Hoon Ryu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Myung Sook Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sun Yeou Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sun Yeou Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ha, S.K., Moon, E., Lee, P. et al. Acacetin Attenuates Neuroinflammation via Regulation the Response to LPS Stimuli In Vitro and In Vivo. Neurochem Res 37, 1560–1567 (2012). https://doi.org/10.1007/s11064-012-0751-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-012-0751-z

Keywords

Search

Navigation