期刊论文详细信息
BMC Complementary and Alternative Medicine
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
Jin Yeul Ma1  Won-Kyung Cho1  Jeong-Ho Ha1  Yun Hee Jeong1  You-Chang Oh1 
[1]Korean Medicine (KM)-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon, Yuseong, Republic of Korea
关键词: Mitogen-activated protein kinase;    Nuclear factor-kappaB;    Heme oxygenase-1;    Inducible nitric oxide synthase;    Oryeongsan;   
Others  :  1087357
DOI  :  10.1186/1472-6882-14-242
 received in 2014-04-03, accepted in 2014-06-30,  发布年份 2014
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【 摘 要 】

Background

Oryeongsan (OR) is an herbal medication used in east-Asian traditional medicine to treat dysuresia, such as urinary frequency, hematuria, and dysuria due to renal disease and chronic nephritis. Recent studies showed that protective effect against acute gastric mucosal injury and an inhibitory effect on the renin-angiotensin-aldosterone pathway of OR. However, its effect on inflammation still remains unknown. In this study, to provide insight into the biological effects of OR, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in the RAW 264.7 macrophage cells.

Methods

We investigated the pharmacological and biological effects of OR on the production of pro-inflammatory cytokines, inflammatory mediators, and related products through Enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Also, we examined the activation and suppression of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) pathways in LPS-stimulated macrophages via Western blot analysis in order to explore inhibitory mechanism of OR.

Results

OR had anti-inflammatory effects by inhibiting the production of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta. In addition, it strongly suppressed cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), NO synthesizing enzymes. It also induced heme oxygenase (HO)-1 expression and inhibited NF-kappaB signaling pathway activation and phosphorylation of MAPKs.

Conclusions

We further demonstrate the anti-inflammatory effects and inhibitory mechanism of OR in LPS-stimulated macrophages for the first time. OR contains strong anti-inflammatory activity and affects various mechanism pathways including NF-kappaB, MAPKs and HO-1. Our results suggest that OR has potential value to be developed as an inflammatory therapeutic agent from a natural substance.

【 授权许可】

   
2014 Oh et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Jeon WY, Lee MY, Shin IS, Lim HS, Shin HK: Protective effects of the traditional herbal formula oryeongsan water extract on ethanol-induced acute gastric mucosal injury in rats. Evid Based Complement Alternat Med 2012, 2012:438191.
  • [2]Ahn YM, Cho KW, Kang DG, Lee HS: Oryeongsan (Wulingsan), a traditional Chinese herbal medicine, induces natriuresis and diuresis along with an inhibition of the renin-angiotensin-aldosterone system in rats. J Ethnopharmacol 2012, 141:780-785.
  • [3]Liu IM, Tzeng TF, Liou SS, Chang CJ: The amelioration of streptozotocin diabetes-induced renal damage by Wu-Ling-San (Hoelen Five Herb Formula), a traditional Chinese prescription. J Ethnopharmacol 2009, 124:211-218.
  • [4]He L, Rong X, Jiang JM, Liu PQ, Li Y: Amelioration of anti-cancer agent adriamycin-induced nephrotic syndrome in rats by Wulingsan (Gorei-San), a blended traditional Chinese herbal medicine. Food Chem Toxicol 2008, 46:1452-1460.
  • [5]Becker S, Mundandhara S, Devlin RB, Madden M: Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: further mechanistic studies. Toxicol Appl Pharmacol 2005, 1:269-275.
  • [6]Pierce GF: Macrophages: important physiologic and pathologic sources of polypeptide growth factors. Am J Respir Cell Mol Biol 1990, 2:233-234.
  • [7]Guslandi M: Nitric oxide and inflammatory bowel diseases. Eur J Clin Invest 1998, 28:904-907.
  • [8]Simons RK, Junger WG, Loomis WH, Hoyt DB: Acute lung injury in endotoxemic rats is associated with sustained circulating IL-6 levels and intrapulmonary CINC activity and neutrophil recruitment–role of circulating TNF-alpha and IL-beta? Shock 1996, 6:39-45.
  • [9]Wadleigh DJ, Reddy ST, Kopp E, Ghosh S, Herschman HR: Transcriptional activation of the cyclooxygenase-2 gene in endotoxin-treated RAW 264.7 macrophages. J Biol Chem 2000, 275:6259-6266.
  • [10]Kim JB, Han AR, Park EY, Kim JY, Cho W, Lee J, Seo EK, Lee KT: Inhibition of LPS-induced iNOS, COX-2 and cytokines expression by poncirin through the NF-kappaB inactivation in RAW 264.7 macrophage cells. Biol Pharm Bull 2007, 30:2345-2351.
  • [11]Pae HO, Chung HT: Heme oxygenase-1: its therapeutic roles in inflammatory diseases. Immune Netw 2009, 9:12-19.
  • [12]Terry CM, Clikeman JA, Hoidal JR, Callahan KS: Effect of tumor necrosis factor-alpha and interleukin-1 alpha on heme oxygenase-1 expression in human endothelial cells. Am J Physiol 1998, 274:883-891.
  • [13]Srisook K, Cha YN: Super-induction of HO-1 in macrophages stimulated with lipopolysaccharide by prior depletion of glutathione decreases iNOS expression and NO production. Nitric Oxide 2005, 12:70-79.
  • [14]Kaur H, Hughes MN, Green CJ, Naughton P, Foresti R, Motterlini R: Interaction of bilirubin and biliverdin with reactive nitrogen species. FEBS Lett 2003, 543:113-119.
  • [15]Wang WW, Smith DL, Zucker SD: Bilirubin inhibits iNOS expression and NO production in response to endotoxin in rats. Hepatology 2004, 40:424-433.
  • [16]Ashino T, Yamanaka R, Yamamoto M, Shimokawa H, Sekikawa K, Iwakura Y, Shioda S, Numazawa S, Yoshida T: Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages. Mol Immunol 2008, 45:2106-2115.
  • [17]Kang SR, Han DY, Park KI, Park HS, Cho YB, Lee HJ, Lee WS, Ryu CH, Ha YL, Lee Do H, Kim JA, Kim GS: Suppressive effect on lipopolysaccharide-induced proinflammatory mediators by citrus aurantium L. In macrophage RAW 264.7 cells via NF-κB signal pathway. Evid Based Complement Alternat Med 2011, 2011:248592.
  • [18]Makarov SS: NF-κB as a therapeutic target in chronic inflammation recent advances. Mol Med Today 2000, 6:441-448.
  • [19]de Martin R, Vanhove B, Cheng Q, Hofer E, Csizmadia V, Winkler H, Bach FH: Cytokine-inducible expression in endothelial cells of an IκBα-like gene is regulated by NF-κB. EMBO J 1993, 12:2773-2779.
  • [20]Pahl HL: Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 1999, 18:6853-6866.
  • [21]Baeuerle PA, Baltimore D: NF-kappa B: ten years after. Cell 1996, 87:13-20.
  • [22]Wu LC, Fan NC, Lin MH, Chu IR, Huang SJ, Hu CY, Han SY: Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS-induced inflammatory mediators. J Agric Food Chem 2008, 56:2341-2349.
  • [23]Gilroy DW, Lawrence T, Perretti M, Rossi AG: Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov 2004, 3:401-416.
  • [24]Robinson MJ, Cobb MH: Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 1997, 9:180-186.
  • [25]Wang X, Martindale JL, Liu Y, Holbrook NJ: The cellular response to oxidative stress: influences of mitogen-activated protein kinase signalling pathways on cell survival. Biochem J 1998, 333(Pt 2):291-300.
  • [26]Kim YH, Lee SH, Lee JY, Choi SW, Park JW, Kwon TK: Triptolide inhibits murine inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-kappa B and c-Jun NH2-terminal kinase. Eur J Pharmacol 2004, 494:1-9.
  • [27]Choi HJ, Kang OH, Park PS, Chae HS, Oh YC, Lee YS, Choi JG, Lee GH, Kweon OH, Kwon DY: Mume Fructus water extract inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated macrophages. J Med Food 2007, 10:460-466.
  • [28]Jo HY, Kim Y, Nam SY, Lee BJ, Kim YB, Yun YW, Ahn B: The inhibitory effect of quercitrin gallate on iNOS expression induced by lipopolysaccharide in Balb/c mice. J Vet Sci 2008, 9:267-272.
  • [29]Kim HY, Kim JK, Choi JH, Jung JY, Oh WY, Kim DC, Lee HS, Kim YS, Kang SS, Lee SH, Lee SM: Hepatoprotective effect of pinoresinol on carbon tetrachloride-induced hepatic damage in mice. J Pharmacol Sci 2010, 112:105-112.
  • [30]Srisook K, Palachot M, Mongkol N, Srisook E, Sarapusit S: Anti-inflammatory effect of ethyl acetate extract from Cissus quadrangularis Linn may be involved with induction of heme oxygenase-1 and suppression of NF-κB activation. J Ethnopharmacol 2011, 133:1008-1014.
  • [31]Kwon DJ, Ju SM, Youn GS, Choi SY, Park J: Suppression of iNOS and COX-2 expression by flavokawain A via blockade of NF-κB and AP-1 activation in RAW 264.7 macrophages. Food Chem Toxicol 2013, 58:479-486.
  • [32]Jang MH, Shin MC, Kim YJ, Kim CJ, Kim Y, Kim EH: Atractylodes japonica suppresses lipopolysaccharide-stimulated expressions of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages. Biol Pharm Bull 2004, 27:324-327.
  • [33]Liao JC, Deng JS, Chiu CS, Hou WC, Huang SS, Shie PH, Huang GJ: Anti-inflammatory activities of cinnamomum cassia constituents in vitro and in vivo. Evid Based Complement Alternat Med 2012, 2012:429320.
  • [34]Han CW, Kwun MJ, Kim KH, Choi JY, Oh SR, Ahn KS, Lee JH, Joo M: Ethanol extract of Alismatis Rhizoma reduces acute lung inflammation by suppressing NF-κB and activating Nrf2. J Ethnopharmacol 2013, 146:402-410.
  • [35]Guzik TJ, Korbut R, Adamek-Guzik T: Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol 2003, 54:469-487.
  • [36]Southan GJ, Szabo C: Selective pharmacological inhibition of distinct nitric oxide synthase isoforms. Biochem Pharmacol 1996, 51:383-394.
  • [37]Brasier AR: The NF-kappaB regulatory network. Cardiovasc Toxicol 2006, 6:111-130.
  • [38]Gilmore TD: Multiple mutations contribute to the oncogenicity of the retroviral oncoprotein v-Rel. Oncogene 1999, 18:6842-6844.
  • [39]Tian B, Brasier AR: Identification of a nuclear factor kappa B-dependent gene network. Recent Pro Hor Res 2003, 58:95-130.
  • [40]Chen F, Kuhn DC, Sun SC, Gaydos LJ, Demers LM: Dependence and reversal of nitric oxide production on NF-kappa B in silica and lipopolysaccharide-induced macrophages. Biochem Biophys Res Commun 1995, 214:839-846.
  • [41]Roshak AK, Jackson JR, McGough K, Chabot-Fletcher M, Mochan E, Marshall LA: Manipulation of distinct NFkappaB proteins alters interleukin-1beta-induced human rheumatoid synovial fibroblast prostaglandin E2 formation. J Biol Chem 1996, 271:31496-31501.
  • [42]Xie W, Merrill JR, Bradshaw WS, Simmons DL: Structural determination and promoter analysis of the chicken mitogen-inducible prostaglandin G/H synthase gene and genetic mapping of the murine homolog. Arch Biochem Biophys 1993, 300:247-252.
  • [43]Ahn KS, Noh EJ, Zhao HL, Jung SH, Kang SM, Kim YS: Inhibition of inducible nitric oxide synthase and cyclooxygenase II by Platycodon grandiflorum saponins via suppression of nuclear factor-kappaB activation in RAW 264.7 cells. Life Sci 2005, 76:2315-2328.
  • [44]Barnes PJ, Karin M: Nuclear factor-kappaB. A pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997, 336:1066-1071.
  • [45]Kim YM, Lee BS, Yi KY, Paik SG: Upstream NF-kappaB site is required for the maximal expression of mouse inducible nitric oxide synthase gene in interferon-gamma plus lipopolysaccharideinduced RAW 264.7 macrophages. Biochem Biophys Res Commun 1997, 236:655-660.
  • [46]Caivano M: Role of MAP kinase cascades in inducing arginine transporters and nitric oxide synthetase in RAW 264.7 macrophages. FEBS Lett 1999, 429:249-253.
  • [47]Li CQ, He LC, Jin JQ: Atractylenolide I and atractylenolide III inhibit Lipopolysaccharide-induced TNF-alpha and NO production in macrophages. Phytother Res 2007, 21:347-353.
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