Neurochemical Research

, Volume 40, Issue 7, pp 1520–1525 | Cite as

Linalool Inhibits LPS-Induced Inflammation in BV2 Microglia Cells by Activating Nrf2

  • Yang Li
  • Ou Lv
  • Fenggang ZhouEmail author
  • Qingsong Li
  • Zhichao Wu
  • Yongri Zheng
Original Paper


Linalool, a natural compound of the essential oils, has been reported to have anti-inflammatory effects. This study aimed to investigate the anti-inflammatory effects and mechanism of linalool in LPS-stimulated BV2 microglia cells. BV2 microglia cells were stimulated with LPS in the presence or absence of linalool. The production of inflammatory mediators TNF-α, IL-1β, NO, and PGE2 as well as Nrf2, HO-1 expression were detected. Our results showed that linalool inhibited LPS-induced TNF-α, IL-1β, NO, and PGE2 production in a dose-dependent manner. Linalool also inhibited LPS-induced NF-κB activation. Treatment of linalool induced nuclear translocation of Nrf2 and expression of HO-1. In addition, our results showed that the anti-inflammatory effect of linalool was attenuated by transfection with Nrf2 siRNA. In conclusion, these results suggested that linalool inhibits LPS-induced inflammation in BV2 microglia cells by activating Nrf2/HO-1 signaling pathway.


Linalool LPS Inflammatory mediators Nrf2 


Conflict of interest

All authors declare that they have no conflict of interest.


  1. 1.
    Sun GY, Shelat PB, Jensen MB, He Y, Sun AY, Simonyi A (2010) Phospholipases A2 and inflammatory responses in the central nervous system. NeuroMol Med 12:133–148CrossRefGoogle Scholar
  2. 2.
    Griffiths M, Neal JW, Gasque P (2007) Innate immunity and protective neuroinflammation: new emphasis on the role of neuroimmune regulatory proteins. Int Rev Neurobiol 82:29–55PubMedCrossRefGoogle Scholar
  3. 3.
    Wang S, Jing H, Yang H, Liu Z, Guo H, Chai L, Hu L (2015) Tanshinone I selectively suppresses pro-inflammatory genes expression in activated microglia and prevents nigrostriatal dopaminergic neurodegeneration in a mouse model of Parkinsons disease. J Ethnopharmacol 164:247–255PubMedCrossRefGoogle Scholar
  4. 4.
    Zhu M, Wang X, Schultzberg M, Hjorth E (2015) Differential regulation of resolution in inflammation induced by amyloid-β42 and lipopolysaccharides in human microglia. J Alzheimers Dis: JAD 43:1237–1250PubMedGoogle Scholar
  5. 5.
    Yan J, Fu Q, Cheng L, Zhai M, Wu W, Huang L, Du G (2014) Inflammatory response in Parkinson’s disease (review). Mol Med Rep 10:2223–2233PubMedGoogle Scholar
  6. 6.
    Heneka MT, Kummer MP, Latz E (2014) Innate immune activation in neurodegenerative disease. Nat Rev Immunol 14:463–477PubMedCrossRefGoogle Scholar
  7. 7.
    Huo M, Cui X, Xue J, Chi G, Gao R, Deng X, Guan S, Wei J, Soromou LW, Feng H, Wang D (2013) Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model. J Surg Res 180:e47–e54PubMedCrossRefGoogle Scholar
  8. 8.
    Peana AT, D’Aquila PS, Panin F, Serra G, Pippia P, Moretti MD (2002) Anti-inflammatory activity of linalool and linalyl acetate constituents of essential oils. Phytomedicine 9:721–726PubMedCrossRefGoogle Scholar
  9. 9.
    Li J, Zhang X, Huang H (2014) Protective effect of linalool against lipopolysaccharide/D-galactosamine-induced liver injury in mice. Int Immunopharmacol 23:523–529PubMedCrossRefGoogle Scholar
  10. 10.
    Deleidi M, Gasser T (2013) The role of inflammation in sporadic and familial Parkinson’s disease. Cell Mol Life Sci: CMLS 70:4259–4273PubMedCrossRefGoogle Scholar
  11. 11.
    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 PI3K/Akt-mediated nuclear transcription factor-κB pathway. Nutr Res 34:1111–1119PubMedCrossRefGoogle Scholar
  12. 12.
    Zhang Y, Chen WA (2015) Biochanin a inhibits lipopolysaccharide-induced inflammatory cytokines and mediators production in BV2 microglia. Neurochem Res 40:165–171PubMedCrossRefGoogle Scholar
  13. 13.
    Chao Y, Wong SC, Tan EK (2014) Evidence of inflammatory system involvement in Parkinson’s disease. BioMed Res Int 2014:308654PubMedCentralPubMedGoogle Scholar
  14. 14.
    Nelson L, Gard P, Tabet N (2014) Hypertension and inflammation in Alzheimer’s disease: close partners in disease development and progression! J Alzheimers Dis: JAD 41:331–343PubMedGoogle Scholar
  15. 15.
    Mizuno T (2012) The biphasic role of microglia in Alzheimer’s disease. Int J Alzheimers Dis 2012:737846PubMedCentralPubMedGoogle Scholar
  16. 16.
    Cianciulli A, Dragone T, Calvello R, Porro C, Trotta T, Lofrumento DD, Panaro MA (2015) IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in activated microglia cells. Int Immunopharmacol 24:369–376PubMedCrossRefGoogle Scholar
  17. 17.
    Kim AR, Lee MS, Choi JW, Utsuki T, Kim JI, Jang BC, Kim HR (2013) Phlorofucofuroeckol A suppresses expression of inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines via inhibition of nuclear factor-κB, c-Jun NH2-terminal kinases, and Akt in microglial cells. Inflammation 36:259–271PubMedCrossRefGoogle Scholar
  18. 18.
    Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–934PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Sun Y, Zhao Y, Yao J, Zhao L, Wu Z, Wang Y, Pan D, Miao H, Guo Q, Lu N (2015) Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB and NLRP3 inflammasome activation. Biochem Pharmacol 94:142–154PubMedCrossRefGoogle Scholar
  20. 20.
    Rai A, Kapoor S, Singh S, Chatterji BP, Panda D (2015) Transcription factor NF-κB associates with microtubules and stimulates apoptosis in response to suppression of microtubule dynamics in MCF-7 cells. Biochem Pharmacol 93:277–289PubMedCrossRefGoogle Scholar
  21. 21.
    Ouyang Z, Zhai Z, Li H, Liu X, Qu X, Li X, Fan Q, Tang T, Qin A, Dai K (2014) Hypericin suppresses osteoclast formation and wear particle-induced osteolysis via modulating ERK signalling pathway. Biochem Pharmacol 90:276–287PubMedCrossRefGoogle Scholar
  22. 22.
    Zhao ZZ, Tang XF, Zhao XH, Zhang MH, Zhang WJ, Hou SH, Yuan WF, Zhang HF, Shi LJ, Jia H, Liang L, Lai Z, Gao JF, Zhang KY, Fu L, Chen W (2014) Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-κB activation. Biochem Pharmacol 90:73–87PubMedCrossRefGoogle Scholar
  23. 23.
    Huang CS, Lin AH, Yang TC, Liu KL, Chen HW, Lii CK (2015) Shikonin inhibits oxidized LDL-induced monocyte adhesion by suppressing NFκB activation via up-regulation of PI3K/Akt/Nrf2-dependent antioxidation in EA. hy926 endothelial cells. Biochem Pharmacol 93:352–361PubMedCrossRefGoogle Scholar
  24. 24.
    Sid B, Glorieux C, Valenzuela M, Rommelaere G, Najimi M, Dejeans N, Renard P, Verrax J, Calderon PB (2014) AICAR induces Nrf2 activation by an AMPK-independent mechanism in hepatocarcinoma cells. Biochem Pharmacol 91:168–180PubMedCrossRefGoogle Scholar
  25. 25.
    Lee BH, Hsu WH, Chang YY, Kuo HF, Hsu YW, Pan TM (2012) Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. Free Radic Biol Med 53:2008–2016PubMedCrossRefGoogle Scholar
  26. 26.
    Lee TM, Lin SZ, Chang NC (2014) Antiarrhythmic effect of lithium in rats after myocardial infarction by activation of Nrf2/HO-1 signaling. Free Radic Biol Med 77:71–81PubMedCrossRefGoogle Scholar
  27. 27.
    Innamorato NG, Rojo AI, Garcia-Yague AJ, Yamamoto M, de Ceballos ML, Cuadrado A (2008) The transcription factor Nrf2 is a therapeutic target against brain inflammation. J Immunol 181:680–689PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Yang Li
    • 1
  • Ou Lv
    • 2
  • Fenggang Zhou
    • 1
    Email author
  • Qingsong Li
    • 1
  • Zhichao Wu
    • 1
  • Yongri Zheng
    • 1
  1. 1.Department of NeurosurgeryThe Second Affiliated Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Department of NeorologyThe Second Affiliated Hospital of Harbin Medical UniversityHarbinChina

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