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http://dx.doi.org/10.4110/in.2010.10.5.145

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)
Publication Information
IMMUNE NETWORK / v.10, no.5, 2010 , pp. 145-152 More about this Journal
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
Inula japonica; Inulae Flos Extract (IFE); Nitric oxide (NO); iNOS; Cytokine; NF-${\kappa}B$; MAP kinase;
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1 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   DOI
2 Johnson GL, Lapadat R: Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298;1911-1912, 2002   DOI   ScienceOn
3 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   DOI   ScienceOn
4 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   DOI   ScienceOn
5 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   DOI   ScienceOn
6 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   DOI   ScienceOn
7 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   DOI   ScienceOn
8 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   DOI   ScienceOn
9 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   DOI
10 Aggarwal BB, Natarajan K: Tumor necrosis factors: developments during the last decade. Eur Cytokine Netw 7;93-124, 1996
11 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   DOI   ScienceOn
12 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   DOI   ScienceOn
13 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   DOI   ScienceOn
14 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   DOI   ScienceOn
15 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   DOI   ScienceOn
16 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   DOI   ScienceOn
17 Geng HM, Zhang DQ, Zha JP, Qi JL: Simultaneous HPLC determination of five flavonoids in flos inulae. Chromatographia 66;271-275, 2007   DOI   ScienceOn
18 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   DOI   ScienceOn
19 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   DOI   ScienceOn
20 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   DOI
21 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   DOI   ScienceOn
22 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   DOI   ScienceOn
23 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   DOI   ScienceOn
24 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
25 Makarov SS: NF-kappaB as a therapeutic target in chronic inflammation: recent advances. Mol Med Today 6;441-448, 2000   DOI   ScienceOn
26 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   DOI   ScienceOn