DOI QR코드

DOI QR Code

Flowers of Inula japonica Attenuate Inflammatory Responses

  • Choi, Jeon-Hyeun (Research and Development Division, Daegu Gyeongbuk Institute for Oriental Medicine Industry) ;
  • Park, Young-Na (Research and Development Division, Daegu Gyeongbuk Institute for Oriental Medicine Industry) ;
  • Li, Ying (College of Pharmacy, Yeungnam University) ;
  • Jin, Mei-Hua (College of Pharmacy, Yeungnam University) ;
  • Lee, Ji-Ean (Research and Development Division, Daegu Gyeongbuk Institute for Oriental Medicine Industry) ;
  • Lee, Youn-Ju (College of Medicine, Yeungnam University) ;
  • Son, Jong-Keun (College of Pharmacy, Yeungnam University) ;
  • Chang, Hyeun-Wook (College of Pharmacy, Yeungnam University) ;
  • Lee, Eun-Kyung (Research and Development Division, Daegu Gyeongbuk Institute for Oriental Medicine Industry)
  • Received : 2010.08.05
  • Accepted : 2010.09.02
  • Published : 2010.10.30

Abstract

Background: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of inflammatory diseases. In the present study, we investigated the anti-inflammatory properties of Inulae Flos Extract (IFE). Methods: The anti-inflammatory effects of IFE against nitric oxide (NO), $PGE_2$, TNF-${\alpha}$, and IL-6 release, as well as NF-${\kappa}B$ and MAP kinase activation were evaluated in RAW 264.7 cells. Results: IFE inhibited the production of NO and the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW264.7 cells. In addition, IFE reduced the release of pro-inflammatory cytokines, such as TNF-${\alpha}$ and IL-6. Furthermore, IFE inhibited the NF-${\kappa}B$ activation induced by LPS, which was associated with the abrogation of $I{\kappa}B-{\alpha}$ degradation and subsequent decreases in nuclear p65 and p50 levels. Moreover, the phosphorylation of ERK, JNK, and p38 MAP kinases in LPS-stimulated RAW 264.7 cells was suppressed by IFE in a dose-dependent manner. Conclusion: These results suggest that the anti-inflammation activities of IFE might be attributed to the inhibition of NO, iNOS and cytokine expression through the down-regulation of NF-${\kappa}B$ activation via suppression of $I{\kappa}B{\alpha}$ and MAP kinase phosphorylation in macrophages.

Keywords

References

  1. Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM:Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 11;821-831, 2003
  2. Makarov SS: NF-kappaB as a therapeutic target in chronic inflammation: recent advances. Mol Med Today 6;441-448, 2000 https://doi.org/10.1016/S1357-4310(00)01814-1
  3. Lappas M, Permezel M, Georgiou HM, Rice GE: Nuclear factor kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro. Biol Reprod 67;668-673, 2002 https://doi.org/10.1095/biolreprod67.2.668
  4. Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS: Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 480-481;243-268, 2001 https://doi.org/10.1016/S0027-5107(01)00183-X
  5. Yamamoto Y, Gaynor RB: Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest 107;135-142, 2001 https://doi.org/10.1172/JCI11914
  6. Geng HM, Zhang DQ, Zha JP, Qi JL: Simultaneous HPLC determination of five flavonoids in flos inulae. Chromatographia 66;271-275, 2007 https://doi.org/10.1365/s10337-007-0285-8
  7. Liu S, Liu H, Yan W, Zhang L, Bai N, Ho CT: Studies on 1-O-acetylbritannilactone and its derivative, (2-O-butyloxime- 3-phenyl)-propionyl-1-O-acetylbritannilactone ester. Bioorg Med Chem Lett 14;1101-1104, 2004 https://doi.org/10.1016/j.bmcl.2003.12.078
  8. Grilli M, Chiu JJ, Lenardo MJ: NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol 143;1-62, 1993 https://doi.org/10.1016/S0074-7696(08)61873-2
  9. Shan JJ, Yang M, Ren JW: Anti-diabetic and hypolipidemic effects of aqueous-extract from the flower of Inula japonica in alloxan-induced diabetic mice. Biol Pharm Bull 29;455- 459, 2006 https://doi.org/10.1248/bpb.29.455
  10. Han M, Wen JK, Zheng B, Zhang DQ: Acetylbritannilatone suppresses NO and PGE2 synthesis in RAW 264.7 macrophages through the inhibition of iNOS and COX-2 gene expression. Life Sci 75;675-684, 2004 https://doi.org/10.1016/j.lfs.2003.12.022
  11. Hernandez V, del Carmen Recio M, Manez S, Prieto JM, Giner RM, Ríos JL: A mechanistic approach to the in vivo anti-inflammatory activity of sesquiterpenoid compounds isolated from Inula viscosa. Planta Med 67;726-731, 2001 https://doi.org/10.1055/s-2001-18342
  12. Hernandez V, Manez S, Recio MC, Giner RM, Rios JL: Anti-inflammatory profile of dehydrocostic acid, a novel sesquiterpene acid with a pharmacophoric conjugated diene. Eur J Pharm Sci 26;162-169, 2005 https://doi.org/10.1016/j.ejps.2005.05.007
  13. Hernandez V, Recio MC, Manez S, Giner RM, Ríos JL: Effects of naturally occurring dihydroflavonols from Inula viscosa on inflammation and enzymes involved in the arachidonic acid metabolism. Life Sci 81;480-488, 2007 https://doi.org/10.1016/j.lfs.2007.06.006
  14. Whan Han J, Gon Lee B, Kee Kim Y, Woo Yoon J, Kyoung Jin H, Hong S, Young Lee H, Ro Lee K, Woo Lee H: Ergolide, sesquiterpene lactone from Inula britannica, inhibits inducible nitric oxide synthase and cyclo-oxygenase- 2 expression in RAW 264.7 macrophages through the inactivation of NF-kappaB. Br J Pharmacol 133;503-512, 2001 https://doi.org/10.1038/sj.bjp.0704099
  15. Yu NJ, Zhao YM, Zhang YZ, Li YF: Japonicins A and B from the flowers of Inula japonica. J Asian Nat Prod Res 8;385-390, 2006 https://doi.org/10.1080/10286020500034832
  16. Bai N, Lai CS, He K, Zhou Z, Zhang L, Quan Z, Zhu N, Zheng QY, Pan MH, Ho CT: Sesquiterpene lactones from Inula britannica and their cytotoxic and apoptotic effects on human cancer cell lines. J Nat Prod 69;531-535, 2006 https://doi.org/10.1021/np050437q
  17. Cheng PY, Lee YM, Wu YS, Chang TW, Jin JS, Yen MH: Protective effect of baicalein against endotoxic shock in rats in vivo and in vitro. Biochem Pharmacol 73;793-804, 2007 https://doi.org/10.1016/j.bcp.2006.11.025
  18. Aggarwal BB, Natarajan K: Tumor necrosis factors: developments during the last decade. Eur Cytokine Netw 7;93-124, 1996
  19. Thanos D, Maniatis T: Identification of the rel family members required for virus induction of the human beta interferon gene. Mol Cell Biol 15;152-164, 1995 https://doi.org/10.1128/MCB.15.1.152
  20. Kim HG, Shrestha B, Lim SY, Yoon DH, Chang WC, Shin DJ, Han SK, Park SM, Park JH, Park HI, Sung JM, Jang Y, Chung N, Hwang KC, Kim TW: Cordycepin inhibits lipopolysaccharide- induced inflammation by the suppression of NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur J Pharmacol 545;192-199, 2006 https://doi.org/10.1016/j.ejphar.2006.06.047
  21. Choi MS, Lee SH, Cho HS, Kim Y, Yun YP, Jung HY, Jung JK, Lee BC, Pyo HB, Hong JT: Inhibitory effect of obovatol on nitric oxide production and activation of NF-kappaB/ MAP kinases in lipopolysaccharide-treated RAW 264.7cells. Eur J Pharmacol 556;181-189, 2007 https://doi.org/10.1016/j.ejphar.2006.10.054
  22. Choi HJ, Eun JS, Park YR, Kim DK, Li R, Moon WS, Park JM, Kim HS, Cho NP, Cho SD, Soh Y: Ikarisoside A inhibits inducible nitric oxide synthase in lipopolysaccharide-stimulated RAW 264.7 cells via p38 kinase and nuclear factor- kappaB signaling pathways. Eur J Pharmacol 601;171- 178, 2008 https://doi.org/10.1016/j.ejphar.2008.09.032
  23. Zingarelli B, Sheehan M, Wong HR: Nuclear factor-kappaB as a therapeutic target in critical care medicine. Crit Care Med 31(1 Suppl);S105-S111, 2003 https://doi.org/10.1097/00003246-200301001-00015
  24. Johnson GL, Lapadat R: Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298;1911-1912, 2002 https://doi.org/10.1126/science.1072682
  25. Kim JH, Kim DH, Baek SH, Lee HJ, Kim MR, Kwon HJ, Lee CH: Rengyolone inhibits inducible nitric oxide synthase expression and nitric oxide production by down-regulation of NF-kappaB and p38 MAP kinase activity in LPS-stimulated RAW 264.7 cells. Biochem Pharmacol 71;1198-1205, 2006 https://doi.org/10.1016/j.bcp.2005.12.031
  26. Suh SJ, Chung TW, Son MJ, Kim SH, Moon TC, Son KH, Kim HP, Chang HW, Kim CH: The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappaB regulation, in RAW264.7 cells. Arch Biochem Biophys 447;136-146, 2006 https://doi.org/10.1016/j.abb.2006.01.016

Cited by

  1. 2,5-Dihydroxyacetophenone Isolated from Rehmanniae Radix Preparata Inhibits Inflammatory Responses in Lipopolysaccharide-Stimulated RAW264.7 Macrophages vol.15, pp.6, 2010, https://doi.org/10.1089/jmf.2011.1940
  2. Inulae Flos and Its Compounds Inhibit TNF- α - and IFN- γ -Induced Chemokine Production in HaCaT Human Keratinocytes vol.2012, pp.None, 2012, https://doi.org/10.1155/2012/280351
  3. Sargachromenol from Sargassum micracanthum Inhibits the Lipopolysaccharide-Induced Production of Inflammatory Mediators in RAW 264.7 Macrophages vol.2013, pp.None, 2010, https://doi.org/10.1155/2013/712303
  4. Chemical Composition and Anti-inflammation Activity of Essential Oils from Citrus unshiu Flower vol.9, pp.5, 2010, https://doi.org/10.1177/1934578x1400900538
  5. Inhibitory Effect of Litchi (Litchi chinensis Sonn.) Flower on Lipopolysaccharide-Induced Expression of Proinflammatory Mediators in RAW264.7 Cells through NF-κB, ERK, and JAK2/STAT3 Inactivatio vol.62, pp.15, 2014, https://doi.org/10.1021/jf5003705
  6. Inhibitory Effects of JEUD-38, a New Sesquiterpene Lactone from Inula japonica Thunb, on LPS-Induced iNOS Expression in RAW264.7 Cells vol.38, pp.3, 2010, https://doi.org/10.1007/s10753-014-0056-2
  7. Anti-Inflammatory Activity of Heterocarpin from the Salt Marsh Plant Corydalis heterocarpa in LPS-Induced RAW 264.7 Macrophage Cells vol.20, pp.8, 2010, https://doi.org/10.3390/molecules200814474
  8. Chemical composition and anti-inflammatory activities of essential oil from Trachydium roylei vol.24, pp.3, 2016, https://doi.org/10.1016/j.jfda.2016.02.009
  9. The combination of herbal medicine Weng-li-tong with Tolterodine may be better than Tolterodine alone in the treatment of overactive bladder in women: a randomized placebo-controlled prospective trial vol.16, pp.None, 2016, https://doi.org/10.1186/s12894-016-0167-1
  10. Ethanol Extracts of Rheum undulatum and Inula japonica Protect Against Oxidative Damages on Human Keratinocyte HaCaT cells through the Induction of ARE/NRF2-dependent Phase II Cytoprotective Enzymes vol.27, pp.3, 2017, https://doi.org/10.5352/jls.2017.27.3.310
  11. 국산 한약재로 이용되는 약용식물의 NCI-H1229 인간 폐암 세포주에 대한 성장 억제효과 분석 vol.26, pp.4, 2010, https://doi.org/10.7783/kjmcs.2018.26.4.281
  12. Essential oil from halophyteLobularia maritima: protective effects against CCl4-induced hepatic oxidative damage in rats and inhibition of the production of proinflammatory gene expression vol.9, pp.63, 2010, https://doi.org/10.1039/c9ra05885k
  13. Nepetin, a natural compound from Inulae flos, suppresses degranulation and eicosanoid generation through PLCγ1 and Akt signaling pathways in mast cells vol.43, pp.2, 2010, https://doi.org/10.1007/s12272-020-01212-7
  14. Analysis of chemical composition of Inula japonica Thunb. extract and in vitro screening for anti-pulmonary fibrosis active components vol.36, pp.None, 2010, https://doi.org/10.1016/j.phytol.2020.02.003
  15. 선복화 에탄올 추출물의 급성 독성 연구 vol.28, pp.2, 2010, https://doi.org/10.14374/hfs.2020.28.2.169
  16. A Review of Phytochemical and Pharmacological Studies of Inula Species vol.16, pp.5, 2010, https://doi.org/10.2174/1573407215666190207093538
  17. Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones vol.9, pp.10, 2021, https://doi.org/10.3390/biomedicines9101325