, Volume 41, Issue 3, pp 835–845 | Cite as

Anti-Inflammatory Effects of Gingerol on Lipopolysaccharide-Stimulated RAW 264.7 Cells by Inhibiting NF-κB Signaling Pathway

  • Na Liang
  • Yaxin Sang
  • Weihua Liu
  • Wenlong Yu
  • Xianghong WangEmail author


Gingerol was the main functional substance of Zingiberaceous plant which has been known as traditional medicine for thousands of years. The purpose of this experiment was to explore anti-inflammatory effects of gingerol and study the possible mechanism in lipopolysaccharide (LPS)-stimulated RAW246.7 cells. The cells were treated with 10 μg/mL LPS and 300, 200, 100, and 50 μg/mL gingerol for 24 h. The cytotoxicity of gingerol was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zoliumbromide (MTT) method. Nitric oxide (NO) production was observed using Griess assays. Prostaglandin E2 (PGE2) and pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 have been analyzed by ELISA. Real-time PCR was used to detect the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-6, and IL-1β in LPS-induced RAW246.7 cells. Nuclear transcription factor kappa-B (NF-κB) signaling pathway-related proteins have been assessed by western blot assays. The determination of MTT showed that cell viability was not significantly affected by up to 300 μg/mL gingerol. Compared with LPS group, 50, 100, 200, and 300 μg/mL gingerol can inhibit the production of NO and the inhibitory rate was 10.4, 29.1, 58.9, and 62.4%, respectively. The results indicated gingerol existed anti-inflammatory effect. In addition, gingerol also observably inhibited LPS-induced TNF-α, IL-1β, IL-6, and PGE2 (p < 0.01) expression and secretion in a dose-dependent manner. At the genetic level, after the intervention of gingerol, mRNA transcriptions of iNOS, COX-2, IL-6, and IL-1β were all decreased. The protein expressions of iNOS, NF-κB, p-p65, and p-IκB were significantly increased in LPS-induced cells, while these changes were reversed by the treatment with gingerol. This study suggested that gingerol exerts its anti-inflammatory activities in LPS-induced macrophages which can inhibit the production of inflammatory cytokines by targeting the NF-κB signaling pathway.


gingerol anti-inflammatory RAW246.7 cells NF-κB 



This study was supported by the agricultural technology system innovation team of Hebei, China.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

10753_2018_737_MOESM1_ESM.docx (37 kb)
ESM 1 (DOCX 36 kb)


  1. 1.
    Zhai, X.-T., J.-Q. Chen, C.-H. Jiang, J. Song, D.-Y. Li, H. Zhang, X.-B. Jia, W. Tan, S.-X. Wang, Y. Yang, and F.-X. Zhu. 2016. Corydalis bungeana Turcz. attenuates LPS-induced inflammatory responses via the suppression of NF-κB signaling pathway in vitro and in vivo. Journal of Ethnopharmacology 194: 153–161.CrossRefPubMedGoogle Scholar
  2. 2.
    Ahn, C.-B., Y.-S. Cho, and J.-Y. Je. 2015. Purification and anti-inflammatory action of tripeptide from salmon pectoral fin byproduct protein hydrolysate. Food Chemistry. 168: 151–156.CrossRefPubMedGoogle Scholar
  3. 3.
    Baldwin, G.S. 2000. Do NSAIDs contribute to acute fatty liver of pregnancy? Medical Hypotheses 54 (5): 846.CrossRefPubMedGoogle Scholar
  4. 4.
    Stuart, M.J., S.J. Gross, H. Elrad, et al. 1982. Effects of acetylsalicylic acid ingestion on maternal and neonatal hemostatic. The New England Journal of Medicine 307: 909.CrossRefPubMedGoogle Scholar
  5. 5.
    Guo, J.-B., Y. Fan, W.-J. Zhang, H. Wu, L.-M. Du, and Y.-X. Chang. 2017. Extraction of gingerols and shogaols from ginger ( Zingiber officinale Roscoe) through microwave technique using ionic liquids. Journal of Food Composition and Analysis 62: 35–42.CrossRefGoogle Scholar
  6. 6.
    Young, H.-Y., Y.-L. Luo, H.-Y. Cheng, W.-C. Hsieh, J.-C. Liao, and W.-H. Peng. 2005. Analgesic and anti-inflammatory activities of [6]-gingerol. Journal of Ethnopharmacology 96 (1–2): 207–210.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhang, F., K. Thakur, F. Hu, J.-G. Zhang, and Z.-J. Wei. 2017. Cross-talk between 10-gingerol and its anti-cancerous potential: A recent update. Food Function 8:2635–2649.CrossRefPubMedGoogle Scholar
  8. 8.
    Brahma Naidu, P., V.V. Uddandrao, R. Ravindar Naik, P. Suresh, B. Meriga, M.S. Begum, R. Pandiyan, and G. Saravanan. 2016. Ameliorative potential of gingerol: Promising modulation of inflammatory factors and lipid marker enzymes expressions in HFD induced obesity in rats. Molecular and Cellular Endocrinology 419: 139–147.CrossRefPubMedGoogle Scholar
  9. 9.
    Li, Y., B. Xu, M. Xu, D. Chen, Y. Xiong, M. Lian, Y. Sun, Z. Tang, L. Wang, C. Jiang, and Y. Lin. 2017. 6-Gingerol protects intestinal barrier from ischemia/reperfusion-induced damage via inhibition of p38 MAPK to NF-kappaB signalling. Pharmacological Research 119: 137–148.CrossRefPubMedGoogle Scholar
  10. 10.
    Gibon, E., L.Y. Lu, K. Nathan, and S.B. Goodman. 2017. Inflammation, ageing, and bone regeneration. Journal of Orthopaedic Translation 10: 28–35.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chen, L.Z., W.W. Sun, L. Bo, J.Q. Wang, C. Xiu, W.J. Tang, J.B. Shi, H.P. Zhou, and X.H. Liu. 2017. New arylpyrazoline-coumarins: Synthesis and anti-inflammatory activity. European Journal of Medicinal Chemistry 138: 170–181.CrossRefPubMedGoogle Scholar
  12. 12.
    Gu, Q., H. Yang, and Q. Shi. 2017. Macrophages and bone inflammation. Journal of Orthopaedic Translation 10: 86–93.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Dong, L., L. Yin, Y. Zhang, X. Fu, and J. Lu. 2017. Anti-inflammatory effects of ononin on lipopolysaccharide-stimulated RAW 264.7 cells. Molecular Immunology 83: 46–51.CrossRefPubMedGoogle Scholar
  14. 14.
    Wu, J., M. Li, L. Liu, Q. An, J. Zhang, J. Zhang, M. Li, W. Duan, D. Liu, Z. Li, and C. Luo. 2013. Nitric oxide and interleukins are involved in cell proliferation of RAW264.7 macrophages activated by viili exopolysaccharides. Inflammation 36 (4): 954–961.CrossRefPubMedGoogle Scholar
  15. 15.
    Jeon, H.J., H.J. Kang, H.J. Jung, Y.S. Kang, C.J. Lim, Y.M. Kim, and E.H. Park. 2008. Anti-inflammatory activity of Taraxacum officinale. Journal of Ethnopharmacology 115 (1): 82–88.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhang, L.B., Z.T. Man, W. Li, W. Zhang, X.Q. Wang, and S. Sun. 2017. Calcitonin protects chondrocytes from lipopolysaccharide-induced apoptosis and inflammatory response through MAPK/Wnt/NF-kappaB pathways. Molecular Immunology 87: 249–257.CrossRefPubMedGoogle Scholar
  17. 17.
    Olbert, M., J. Gdula-Argasinska, G. Nowak, and T. Librowski. 2017. Beneficial effect of nanoparticles over standard form of zinc oxide in enhancing the anti-inflammatory activity of ketoprofen in rats. Pharmacological Reports 69 (4): 679–682.CrossRefPubMedGoogle Scholar
  18. 18.
    Sheeba, M.S., and V.V. Asha. 2009. Cardiospermum halicacabum ethanol extract inhibits LPS induced COX-2, TNF-alpha and iNOS expression, which is mediated by NF-kappaB regulation, in RAW264.7 cells. Journal of Ethnopharmacology 124 (1): 39–44.CrossRefPubMedGoogle Scholar
  19. 19.
    Bockerstett, K.A., and R.J. DiPaolo. 2017. Regulation of gastric carcinogenesis by inflammatory cytokines. Cellular and Molecular Gastroenterology and Hepatology. 4 (1): 47–53.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Chu, C.Q. 2016. Molecular probing of TNF: From identification of therapeutic target to guidance of therapy in inflammatory diseases. Cytokine 101: 64–69.CrossRefPubMedGoogle Scholar
  21. 21.
    Hu, P., G.M. Jiang, Y. Wu, B.Y. Huang, S.Y. Liu, D.D. Zhang, Y. Xu, Y.F. Wu, X. Xia, W. Wei, and B. Hu. 2017. TNF-alpha is superior to conventional inflammatory mediators in forecasting IVIG nonresponse and coronary arteritis in Chinese children with Kawasaki disease. Clinica chimica acta. International Journal of Clinical Chemistry 471: 76–80.PubMedGoogle Scholar
  22. 22.
    Parameswaran, N., and S. Patial. 2010. Tumor necrosis factor-α signaling in macrophages. Critical Reviews™ in. Eukaryotic Gene Expression 20: 87–103.CrossRefGoogle Scholar
  23. 23.
    Szot, P., A. Franklin, D.P. Figlewicz, T.P. Beuca, K. Bullock, K. Hansen, W.A. Banks, M.A. Raskind, and E.R. Peskind. 2017. Multiple lipopolysaccharide (LPS) injections alter interleukin 6 (IL-6), IL-7, IL-10 and IL-6 and IL-7 receptor mRNA in CNS and spleen. Neuroscience 355: 9–21.CrossRefPubMedGoogle Scholar
  24. 24.
    Seppola, M., A.N. Larsen, K. Steiro, B. Robertsen, and I. Jensen. 2008. Characterisation and expression analysis of the interleukin genes, IL-1beta, IL-8 and IL-10, in Atlantic cod (Gadus morhua L.). Molecular Immunology 45 (4): 887–897.CrossRefPubMedGoogle Scholar
  25. 25.
    Yang, Q., Q. Chu, X. Zhao, and T. Xu. 2017. Characterization of IL-1beta and two types of IL-1 receptors in miiuy croaker and evolution analysis of IL-1 family. Fish Shellfish Immunology 63: 165–172.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhou, L., and D.Y. Zhu. 2009. Neuronal nitric oxide synthase: Structure, subcellular localization, regulation, and clinical implications. Nitric Oxide-Biology and Chemistry 20 (4): 223–230.CrossRefPubMedGoogle Scholar
  27. 27.
    Bredt, D.S. 2009. Endogenous nitric oxide synthesis: Biological functions and pathophysiology. Free Radical Research 31 (6): 577–596.CrossRefGoogle Scholar
  28. 28.
    Manferdini, C., F. Paolella, E. Gabusi, L. Gambari, A. Piacentini, G. Filardo, S. Fleury-Cappellesso, A. Barbero, M. Murphy, and G. Lisignoli. 2017. Adipose stromal cells mediated switching of the pro-inflammatory profile of M1-like macrophages is facilitated by PGE2: In vitro evaluation. Osteoarthritis and Cartilage 25 (7): 1161–1171.CrossRefPubMedGoogle Scholar
  29. 29.
    Liu, N., Y. Zhuang, Z. Zhou, J. Zhao, Q. Chen, and J. Zheng. 2017. NF-kappaB dependent up-regulation of TRPC6 by Abeta in BV-2 microglia cells increases COX-2 expression and contributes to hippocampus neuron damage. Neuroscience Letters 651: 1–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Katanić, J., T. Boroja, V. Mihailović, S. Nikles, S.-P. Pan, G. Rosić, D. Selaković, J. Joksimović, S. Mitrović, and R. Bauer. 2016. In vitro and in vivo assessment of meadowsweet (Filipendula ulmaria) as anti-inflammatory agent. Journal of Ethnopharmacology 193: 627–636.CrossRefPubMedGoogle Scholar
  31. 31.
    Perkins, N.D. 1997. Achieving transcriptional specificity with NF-ĸB. Int J Biochem Cell B 29: 1433–1448.CrossRefGoogle Scholar
  32. 32.
    Oeckinghaus, A., and S. Ghosh. 2009. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harbor Perspectives in Biology 1 (4): a000034.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Gong, J., Q. Chen, Y. Yan, and G. Pang. 2014. Effect of casein glycomacropeptide on subunit p65 of nuclear transcription factor-κB in lipopolysaccharide-stimulated human colorectal tumor HT-29 cells. Food Science and Human Wellness 3 (2): 51–55.CrossRefGoogle Scholar
  34. 34.
    Oh, Y.C., Y.H. Jeong, J.H. Ha, et al. 2014. Oryeongsan inhibits LPS-induced production of inflammatory mediators via blockade of the NF-kappaB, MAPK pathways and leads to HO-1 induction in macrophage cells[J]. BMC Complementary and Alternative Medicine 14: 242.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Gugasyan, R., R. Grumont, M. Grossmann, et al. 2000. Rel/NF-kappaB transcription factors: Key mediators of B-cell activation[J]. Immunological Reviews 176: 134–140.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Na Liang
    • 1
  • Yaxin Sang
    • 1
    • 2
  • Weihua Liu
    • 1
    • 2
  • Wenlong Yu
    • 1
  • Xianghong Wang
    • 1
    • 2
    Email author
  1. 1.Faculty of Food Science and TechnologyAgricultural University of HebeiBaodingPeople’s Republic of China
  2. 2.Hebei Research Center of Primary Products Processing TechnologyBaodingPeople’s Republic of China

Personalised recommendations