DOI QR코드

DOI QR Code

Smilax guianensis Vitman Extract Prevents LPS-Induced Inflammation by Inhibiting the NF-κB Pathway in RAW 264.7 Cells

  • Kim, Ju Gyeong (School of Food Science and Biotechnology, Kyungpook National University) ;
  • Kim, Min Jeong (School of Food Science and Biotechnology, Kyungpook National University) ;
  • Lee, Ji Su (Division of Bioengineering, Incheon National University) ;
  • Sydara, Kongmany (Ministry of Health, Institute of Traditional Medicine) ;
  • Lee, Sangwoo (International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Byun, Sanguine (Department of Biotechnology, Yonsei University) ;
  • Jung, Sung Keun (School of Food Science and Biotechnology, Kyungpook National University)
  • Received : 2019.11.19
  • Accepted : 2020.03.22
  • Published : 2020.06.28

Abstract

Nutraceutical treatments can reduce inflammation and prevent the development of inflammatory diseases. In this study, the anti-inflammatory effects of Smilax guianensis Vitman extract (SGE) were examined. SGE suppressed lipopolysaccharide (LPS)-mediated nitrite production in RAW 264.7 cells. SGE also prevented the LPS-induced expression of inducible nitric oxide synthase (iNOS) but not cyclooxygenase (COX)-2. Western blot analysis showed that SGE attenuated LPS-induced phosphorylation of IκB kinase (IKK), inhibitor of kappa B (IκB), and p65. Additionally, SGE inhibited LPS-induced IκB degradation in RAW 264.7 cells. Western blot analysis of the cytosolic and nuclear fractions, as well as immunofluorescence assay results, revealed that SGE suppressed LPS-induced p65 nuclear translocation in RAW 264.7 cells. Moreover, SGE reduced LPS-induced interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA expression and IL-1β and IL-6 protein expression in RAW 264.7 cells. Collectively, these results indicate that SGE suppresses the NF-κB signaling pathway and thereby inhibits the production of NO, IL-1β, and IL-6.

Keywords

References

  1. Finlay BB, McFadden G. 2006. Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell 124: 767-782. https://doi.org/10.1016/j.cell.2006.01.034
  2. Schepetkin IA, Quinn MT. 2006. Botanical polysaccharides: macrophage immunomodulation and therapeutic potential. Int. Immunopharmacol. 6: 317-333. https://doi.org/10.1016/j.intimp.2005.10.005
  3. Frattaruolo L, Carullo G, Brindisi M, Mazzotta S, Bellissimo L, Rago V, et al. 2019. Antioxidant and anti-inflammatory activities of flavanones from Glycyrrhiza glabra L. (licorice) leaf phytocomplexes: identification of licoflavanone as a modulator of NF-kB/MAPK pathway. Antioxidants 8: 186. https://doi.org/10.3390/antiox8060186
  4. Yu R, Li Q, Feng Z, Cai L, Xu Q. 2019. m6A reader YTHDF2 regulates LPS-induced inflammatory response. Int. J. Mol. Sci. 20: 1323. https://doi.org/10.3390/ijms20061323
  5. Korhonen R, Lahti A, Kankaanranta H, Moilanen E. 2005. Nitric oxide production and signaling in inflammation. Curr. Drug Targets Inflamm. Allergy 4: 471-479. https://doi.org/10.2174/1568010054526359
  6. McAdam E, Haboubi HN, Forrester G, Eltahir Z, Spencer-Harty S, Davies C, et al. 2012. Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) are important mediators of reflux-induced cell signalling in esophageal cells. Carcinogenesis 33: 2035-2043. https://doi.org/10.1093/carcin/bgs241
  7. Zhang LN, Zheng JJ, Zhang L, Gong X, Huang H, Wang CD, et al. 2011. Protective effects of asiaticoside on septic lung injury in mice. Exp. Toxicol. Pathol. 63: 519-525. https://doi.org/10.1016/j.etp.2010.04.002
  8. Hwang JH, Kim KJ, Ryu SJ, Lee BY. 2016. Caffeine prevents LPS-induced inflammatory responses in RAW264.7 cells and zebrafish. Chem. Biol. Interact. 248: 1-7. https://doi.org/10.1016/j.cbi.2016.01.020
  9. Yun CH, Jang EJ, Kwon SC, Lee MY, Lee SK, SR Oh, et al. 2015. A Novel synthetic compound, YH-1118, inhibited LPS-induced inflammatory response by suppressing $I{\kappa}B$ kinase/NF-${\kappa}B$ pathway in Raw 264.7 cells. J. Microbiol. Biotechnol. 25: 1047-1055. https://doi.org/10.4014/jmb.1504.04027
  10. Kim EA, Kim SY, Ye BR, Kim J, Ko SC, Lee WW, et al. 2018. Anti-inflammatory effect of Apo-9'-fucoxanthinone via inhibition of MAPKs and NF-kB signaling pathway in LPS-stimulated RAW 264.7 macrophages and zebrafish model. Int. Immunopharmacol. 59: 339-346. https://doi.org/10.1016/j.intimp.2018.03.034
  11. Palombo EA. 2011. Traditional medicinal plant extracts and natural products with activity against oral bacteria: Potential application in the prevention and treatment of oral diseases. Evid.-Based. Complement Alternat Med. 2011: 680354. https://doi.org/10.1093/ecam/nep067
  12. Zubair M, Rizwan K, Rashid U, Saeed R, Saeed AA, Rasool N, et al. 2017. GC/MS profiling, in vitro antioxidant, antimicrobial and haemolytic activities of Smilax macrophylla leaves. Arab. J. Chem. 10: S1460-S1468. https://doi.org/10.1016/j.arabjc.2013.04.024
  13. Ferrufino-Acosta L. 2010. Taxonomic revision of the genus smilax (Smilacaceae)in central America and the Caribbean Islands. Willdenowia 40: 227-280. https://doi.org/10.3372/wi.40.40208
  14. Moncada S, Higgs E. 1995. Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEB J. 9: 1319-1330. https://doi.org/10.1096/fasebj.9.13.7557022
  15. Shan J, Fu J, Zhao Z, Kong X, Huang H, Luo L, et al. 2009. Chlorogenic acid inhibits lipopolysaccharide-induced cyclooxygenase-2 expression in RAW264. 7 cells through suppressing NF-${\kappa}B$ and JNK/AP-1 activation. Int. Immunopharmacol. 9: 1042-1048. https://doi.org/10.1016/j.intimp.2009.04.011
  16. Tak PP, Firestein GS. 2001. NF-kappaB: a key role in inflammatory diseases. J. Clin. Invest. 107: 7-11. https://doi.org/10.1172/JCI11830
  17. Huang TH, Tran VH, Duke RK, Tan S, Chrubasik S, Roufogalis BD, et al. 2006. Harpagoside suppresses lipopolysaccharide-induced iNOS and COX-2 expression through inhibition of NF-kappa B activation. J. Ethnopharmacol. 104: 149-155. https://doi.org/10.1016/j.jep.2005.08.055
  18. Wilms H, Sievers J, Rickert U, Rostami-Yazdi M, Mrowietz U, Lucius R. 2010. Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-$1{\beta}$, TNF-$\alpha$ and IL-6 in an in-vitro model of brain inflammation. J. Neuroinflammation 7: 30. https://doi.org/10.1186/1742-2094-7-30
  19. Brooks MN, Rajaram MV, Azad AK, Amer AO, Valdivia-Arenas MA, Park JH, et al. 2011. NOD2 controls the nature of the inflammatory response and subsequent fate of Mycobacterium tuberculosis and M. bovis BCG in human macrophages. Cell Microbiol. 13: 402-418. https://doi.org/10.1111/j.1462-5822.2010.01544.x
  20. Kumagai Y, Sobajima J, Higashi M, Ishiguro T, Fukuchi M, Ishibashi K, et al. 2015. Coexpression of COX-2 and iNOS in angiogenesis of superficial esophageal squamous cell carcinoma. Int. Surg. 100: 733-743. https://doi.org/10.9738/INTSURG-D-14-00234.1
  21. Zhou MM, Zhang WY, Li RJ, Guo C, Wei SS, Tian XM, et al. 2018. Anti-inflammatory activity of khayandirobilide A from Khaya senegalensis via NF-kappaB, AP-1 and p38 MAPK/Nrf2/HO-1 signaling pathways in lipopolysaccharide-stimulated RAW 264.7 and BV-2 cells. Phytomedicine 42: 152-163. https://doi.org/10.1016/j.phymed.2018.03.016
  22. Tsai HH, Lee WR, Wang PH, Cheng KT, Chen YC, Shen SC. 2013. Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-kappaB and AP-1 activation in macrophages. J. Dermatol. Sci. 69: 122-131. https://doi.org/10.1016/j.jdermsci.2012.10.009
  23. Chu Q, Hashimoto K, Satoh K, Wang Q, Sakagami H. 2009. Effect of three herbal extracts on NO and PGE2 production by activated mouse macrophage-like cells. In Vivo 23: 537-544.
  24. Hong CH, Hur SK, Oh O-J, Kim SS, Nam KA, Lee SK. 2002. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J. Ethnopharmacol. 83: 153-159. https://doi.org/10.1016/S0378-8741(02)00205-2
  25. Kim M-J, Lee J, Kim SS, Seong KC, Lim CK, Park KJ, et al. 2018. Anti-inflammatory activities of Olea europaea extracts from Jeju Island on LPS-induced RAW 264.7 cells. Korean J. Food Preserv. 25: 557-563. https://doi.org/10.11002/kjfp.2018.25.5.557
  26. Jeong YE, Lee MY. 2018. Anti-inflammatory activity of Populus deltoides leaf extract via modulating NF-kappaB and p38/JNK Pathways. Int. J. Mol. Sci. 19: 3746. https://doi.org/10.3390/ijms19123746
  27. van den Berg R, Haenen GRMM, van den Berg H, Bast A. 2007. Transcription factor NF-${\kappa}B$ as a potential biomarker for oxidative stress. Br. J. Nutr. 86: S121-S127. https://doi.org/10.1079/bjn2001340
  28. Viatour P, Merville MP, Bours V, Chariot A. 2005. Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem. Sci. 30: 43-52. https://doi.org/10.1016/j.tibs.2004.11.009
  29. Kong F, Lee BH, Wei K. 2019. 5-Hydroxymethylfurfural mitigates lipopolysaccharide-stimulated inflammation via suppression of MAPK, NF-kappaB and mTOR activation in RAW 264.7 Cells. Molecule 24: 275. https://doi.org/10.3390/molecules24020275
  30. Fan C, Wu LH, Zhang GF, Xu F, Zhang S, Zhang X, et al. 2017. 4'-Hydroxywogonin suppresses lipopolysaccharide-induced inflammatory responses in RAW 264.7 macrophages and acute lung injury mice. PLoS One 12: e0181191. https://doi.org/10.1371/journal.pone.0181191
  31. Jung YJ, Jung JI, Cho HJ, Choi MS, Sung MK, Yu R, et al. 2014. Berteroin present in cruciferous vegetables exerts potent antiinflammatory properties in murine macrophages and mouse skin. Int. J. Mol. Sci. 15: 20686-20705. https://doi.org/10.3390/ijms151120686
  32. Noman AS, Koide N, Hassan F, I IE-K, Dagvadorj J, Tumurkhuu G, et al. 2009. Thalidomide inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production via down-regulation of MyD88 expression. Innate. Immun. 15: 33-41. https://doi.org/10.1177/1753425908099317
  33. Wang P, Qiao Q, Li J, Wang W, Yao LP, Fu YJ. 2016. Inhibitory effects of geraniin on LPS-induced inflammation via regulating NFkappaB and Nrf2 pathways in RAW 264.7 cells. Chem. Biol. Interact. 253: 134-142. https://doi.org/10.1016/j.cbi.2016.05.014
  34. Shin JS, Kang SY, Lee HH, Kim SY, Lee DH, Jang DS, et al. 2020. Patriscabrin F from the roots of Patrinia scabra attenuates LPSinduced inflammation by downregulating NF-${\kappa}B$, AP-1, IRF3, and STAT1/3 activation in RAW 264.7 macrophages. Phytomedicine 68: 153167. https://doi.org/10.1016/j.phymed.2019.153167
  35. Choi WS, Seo YB, Shin PG, Kim WY, Lee SY, Choi YJ, et al. 2015. Veratric acid inhibits iNOS expression through the regulationof PI3K activation and histone acetylationin LPS-stimulated RAW264.7 cells. Int. J. Mol. Med. 35: 202-210. https://doi.org/10.3892/ijmm.2014.1982
  36. Yao F, Xue Q, Li K, Cao X, Sun L, Liu Y. 2019. Phenolic compounds and ginsenosides in ginseng shoots and their antioxidant and antiinflammatory capacities in LPS-induced RAW264.7 mouse macrophages. Int. J. Mol. Sci. 20: 2951. https://doi.org/10.3390/ijms20122951
  37. Kim SY, Kook KE, Kim CH, Hwang JK. 2018. Inhibitory effects of Curcuma xanthorrhiza supercritical extract and xanthorrhizol on LPS-induced inflammation in HGF-1 Cells and RANKL-induced osteoclastogenesis in RAW264.7 cells. J. Microbiol. Biotechnol. 28: 1270-1281. https://doi.org/10.4014/jmb.1803.03045
  38. Dinarello CA. 2018. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol. Rev. 281: 8-27 https://doi.org/10.1111/imr.12621
  39. Tanaka T, Narazaki M, Kishimoto T. 2014. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 6: a016295. https://doi.org/10.1101/cshperspect.a016295
  40. Popa C, Netea MG, van Riel PL, van der Meer JW, Stalenhoef AF. 2007. The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J. Lipid Res. 48: 751-762. https://doi.org/10.1194/jlr.R600021-JLR200
  41. Jung HW, Seo UK, Kim JH, Leem KH, Park YK. 2009. Flower extract of Panax notoginseng attenuates lipopolysaccharide-induced inflammatory response via blocking of NF-kappaB signaling pathway in murine macrophages. J. Ethnopharmacol. 122: 313-319. https://doi.org/10.1016/j.jep.2008.12.024

Cited by

  1. Barringtonia augusta Kurz 추출물의 항염증 및 항산화 효능 평가 vol.53, pp.2, 2021, https://doi.org/10.9721/kjfst.2021.53.2.154
  2. Anti-Inflammatory and Antioxidant Effects of Soroseris hirsuta Extract by Regulating iNOS/NF-κB and NRF2/HO-1 Pathways in Murine Macrophage RAW 264.7 Cells vol.11, pp.10, 2020, https://doi.org/10.3390/app11104711
  3. Anti-inflammatory activities of Italian Chestnut and Eucalyptus honeys on murine RAW 264.7 macrophages vol.87, 2020, https://doi.org/10.1016/j.jff.2021.104752