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Recent Advances in Anti-inflammatory Flavonoid Research since 2004  

Kim Hyun-Pyo (College of Pharmacy, Kangwon National University)
Publication Information
Biomolecules & Therapeutics / v.14, no.1, 2006 , pp. 11-18 More about this Journal
Abstract
Certain flavonoids possess anti-inflammatory activity. Besides their antioxidative property, the cellular action mechanisms of flavonoids include an inhibition of arachidonate metabolizing enzymes such as cyclooxygenases and lipoxygenases, and a down-regulation of proinflammatory gene expression such as cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-$\alpha$. In this review, the recent findings of anti-inflammatory flavonoid research since 2004 were summarized. And the cellular mechanisms on signal transduction pathways were also discussed.
Keywords
flavonoid; anti-inflammation; cyclooxygenase; nitric oxide synthase; gene expression; transcription factor;
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1 Kim, M-J., Ryu, G. R., Kang, J-H., Sim, S. S., Min, D. S., Rhie, D-J., Yoon, S. H., Hahn, S. J., Jeong, I-K., Hong, K-J., Kim, M-S. and Jo, Y-H. (2004). Inhibitory effects of epicatechin on interleukin-1$\beta$-induced inducible nitric oxide synthase expression in RINm5F cells and rat pancreatic islets by down-regulation of NF-$\kappa$B activation. Biochem. Pharmacol. 68, 1775-1785   DOI   ScienceOn
2 Martinez-Florez, S., Gutierrez-Fernandez, B., Sanchez-Campos, S., Gonzalez-Gallego, J. and Tunon, M. J. (2005). Quercetin attenuates nuclear factor-$\kappa$B activation and nitric oxide production in interleukin-1$\beta$-activated rat hepatocytes. J. Nutr. 135, 1359-1365
3 Abad, M. J., Bennejo, P., Alvarez, M., Guerra, J. A, Silvan, A. M. and Villar, A. M. (2004). Flavonoids and a sesquiterpene lactone from Tanacetum microphyllum inhibit anti-inflammatory mediators in LPS-stimulated mouse peritoneal macrophages. Planta Med. 70, 34-38   DOI   ScienceOn
4 Blonska, M., Bronikowska, J., Pietsz, G., Czuba, Z. P., Scheller, S. and Krol, W. (2004). Effects of ethanol extract of propolis (EEP) and its flavones on inducible gene expression in J774A.l macrophages. J. Ethnopharmacol. 91,25-30   DOI   ScienceOn
5 Cheon, B. S., Kim, Y. H., Son, K. S., Chang, H. W., Kang, S. S. and Kim, H. P. (2000). Effects of prenylated flavonoids and biflavonoids on lipopolysaccharide-induced nitric oxide production from the mouse macrophage cell line, RAW 264.7. Planta Med. 66, 596-600   DOI   ScienceOn
6 Chang, Y. L., Shen, J. J., Wung, B. S., Chen, J. J. and Wang, D. L. (2001). Chinese herbal remedy wogonin inhibits monocyte chemotactic protein-1 gene expression in human endothelial cells. Mol. Phamacol. 60. 507-513
7 Chen, C-J., Raung, S-L., Liao, S-L. and Chen, S-Y. (2004). Inhibition of inducible nitric oxide synthase expression by baicalein in endotoxinlcytokine-stimulated microglia. Biochem. Pharmacol. 67, 957-965   DOI   ScienceOn
8 Chen, J-c., Ho, F-M., Chao, P-D. L., Chen, C-P., Jeng, K-C. G, Hsu, H-B., Lee, S-T., Wu, W. T. and Lin, W-w. (2005). Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IKB kinase, nuclear factor-kappa B and STATl, and depends on heme oxygenase-l induction in mouse BV-2 microglia. Eur. J. Pharmacol. 521,9-20   DOI   ScienceOn
9 Chi, Y. S., Cheon, B. S. and Kim, H. P. (2001a). Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells. Biochem. Pharmacol. 61,11l95-1203   DOI   ScienceOn
10 Chi, Y. S., Jong, H. G., Son, K. H., Chang, H. W., Kang, S. S. and Kim, H. P. (2001b). Effects of naturally occurring prenylated flavonoids on enzymes metabolizing arachidonic acid: Cyclo-oxygenases and lipoxygenases. Biochem. Pharmacol. 62, 1185-1191   DOI   ScienceOn
11 Chuang, H-N., Wang, J-Y., Chiu, J-H., Tsai, T. H., Yeh, S. F., Fu, S. L., Lui, W. Y. and Wu, C. W. (2005). Enhancing effects of Scutellaria baicalensis and some of its constituents on TGF- $\beta$1 gene expression in RAW 264.7 murine macrophage cell line. Planta Med. 71, 440-445   DOI   ScienceOn
12 Hou, D-X., Yanagita, T., Uto, T., Masuzaki, S. and Fujii, M. (2005). Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages: Structure-activity relationship and molecular mechanisms involved. Biochem. Phannacol. 70, 417-425   DOI   ScienceOn
13 Dao, T. T., Chi, Y. S., Kim, J., Kim, H. P., Kim, S. and Park, H. (2004). Synthesis and inhibitory activity against COX-2 catalyzed prostaglandin production of chrysin derivatives. Bioorg. Med. Chern. Lett. 14, 1165-1167   DOI   ScienceOn
14 Furuhashi, I., Iwata, S., Shibata, S., Sato, T. and Inoue, H. (2005). Inhibition by licochalcone A, a novel flavonoid isolated from liquorice root of IL-1$\beta$-induced $PGE_{2}$ production in human skin fibroblasts. J. Pharm. Pharmacol. 57, 1661-1666   DOI   ScienceOn
15 Hirano, T., Higa, S., Arimitsu, J., Naka, T., Ogata, A., Shima, Y., Fujimoto, M., Yamadori, T., Ohkawara, T., Kuwabara, Y., Kawai, M., Matsuda, H., Yoshiawa, M., Maezaki, N., Tanaka, T., Kawase, I. and Tanaka, T. (2006). Luteolin, a flavonoid, inhibits AP-l activation by basophils. Biochem. Biophys. Res.Comm. 340, 1-7   DOI   ScienceOn
16 Hu, C. and Kitts, D. D. (2004). Luteolin and luteolin-7-O-glucoside from dandelion flower suppress iNOS and COX-2 in RAW264.7 cells. Mol. Cell. Biochem. 265,107-113   DOI   ScienceOn
17 Hu, X. M., Zhou, M. M., Hu, X. M. and Zeng, F. D. (2005). Neuroprotective effects of scutellarin on rat neuronal damage induced by cerebral ischemia/reperfusion. Acta Pharmacol. Sin. 26, 1454-1459   DOI   ScienceOn
18 Kim, A. R., Cho, J. Y., Zou, Y., Choi, J. S. and Chung, H. Y. (2005). Flavonoids differentially modulate nitric oxide production pathways in lipopolysaccharide-activated RAW 264.7 cells. Arch. Pharm. Res. 28,297-304   과학기술학회마을   DOI
19 Kim, H. K., Cheon, B. S., Kim, Y. H., Kim, S. Y. and Kim, H. P. (1999). Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure-activity relationships. Biochem. Pharmacol. 58, 759-765   DOI   ScienceOn
20 Kim, H., Kim, Y. S., Kim, S. Y. and Suk, K. (2001). The flavonoid wogonin suppresses death of activated C6 rat glial cells by inhibiting nitric oxide production. Neurosci. Lett. 309, 67-71   DOI   ScienceOn
21 Kim, J-A., Kim, D-K., Kang, O-H., Choi, Y-A., Park, H-J., Choi, S-C., Kim, T-H., Yun, K-J., Nah, Y-H. and Lee, Y-M. (2005). Inhibitory effect of luteolin on TNF-$\alpha$-induced IL-8 production in human colon epithelial cells. Int. Immunopharmacol. 5, 209-217   DOI   ScienceOn
22 Kim, S. J., Park, H. and Kim, H. P. (2004). Inhibition of nitric oxide production from lipopolysaccharide-treated RAW 264.7 cells by synthetic flavones: Structure-activity relationship and action mechanism. Arch. Pharm. Res. 27,937-943   DOI   ScienceOn
23 Kobuchi, H., Roy, S., Sen, C. K., Nguyen, H. G. and Packer, L. (1999). Quercetin inhibits inducible ICAM-l expression in human endothelial cells through the JNK pathway. Am. J. Physiol. 277 (Cell PhysioI. 46), C403-C411   DOI
24 Kowalski, J., Samojedny, A., Paul, M., Pietsz, G. and Wilczak, T. (2005a) Effect of apigenin, kaempherol and resveratrol on the expression of interleukin-1$\beta$, and tumor necrosis factor-$\alpha$ genes in 1774.2 macrophages. Pharmacol. Reports 57, 390-394
25 Cho, J. and Lee, H-K. (2004). Wogonin inhibits excitotoxic and oxidative neuronal damage in primary cultured rat cortical cells. Eur. J. Pharmacol. 485, 105-110   DOI   ScienceOn
26 Ludwig, A., Lorenz, M., Grimbo, N., Steinle, F., Meiners, S., Bartsch, C., Stangl, K., Baumann, G. and Stangl, V. (2004). The tea flavonoid epigallocatechin-3-gallate reduces cytokineinduced YCAM-1 expression and monocyte adhesion to endothelial cells. Biochem. Biophys. Res. Comm. 316, 659-665   DOI   ScienceOn
27 Kwak, W. J., Moon, T. C., Lin, C. X., Rhyn, H. G., Jung, H., Lee, E., Kwon, D. Y., Son, K. H., Kim, H. P., Kang, S. S., Murakami, M., Kudo, I. and Chang, H. W. (2003). Papyriflavonol A from Broussonetia papyrifera inhibits the passive cutaneous anaphylaxis reaction and has a secretory phospholipase $A_{2}$-inhibitory activity. Biol. Pharm. Bull. 26, 299-302   DOI   ScienceOn
28 Liang, Y. C., Huang, Y. T., Tsai, S. H., Lin-Shiau, S. Y., Chen, C. F. and Lin, J. K. (1999). Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis 20, 1945-1952   DOI   ScienceOn
29 Lim, B. O. (2004). Efficacy of wogonin in the production of immunoglobulins and cytokines by mesenteric lymph node lymphocytes in mouse colitis induced with dextran sulfate sodium. Biosci. Biotechnol. Biochem. 68, 2505-2511   DOI   ScienceOn
30 Middleton, E., Kandaswami, C. and Theoharides, T. C. (2000). The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol. Rev. 52,673-751
31 Murakami, M. and Kudo, I. (2004). Recent advances in molecular biology and physiology of the prostaglandin $E_{2}$-biosynthetic pathway. Progress in Lipid Res. 43, 3-35   DOI   ScienceOn
32 Park, J., Kim, S. H. and Kim, T. S. (2006). Inhibition of interleukin- 4 production in activated T cells via down-regulation of NF-AT DNA binding activity by apigenin, a flavonoid present in dietary plants. Immunol. Lett. 103, 108-114   DOI   ScienceOn
33 Kang, B. Y., Kim, S. H., Cho, D. and Kim, T. S. (2005). Inhibition of interleukin-12 production in mouse macrophages via decreased nuclear factor-$\kappa$B DNA binding activity by myricetin, a naturally occurring flavonoid. Arch. Pharm. Res. 28, 274-279   과학기술학회마을   DOI
34 Pandey, R., Maruya, R, Singh, G., Sathiamoorhy, B. and Naik, S. (2005). Immunosuppressive properties of flavonoids isolated from Boerhaavia diffusa Linn. Int. Immunopharmacol. 5, 541-553   DOI   ScienceOn
35 Parente, L. and Perretti, M. (2003). Advances in the pathophysiology of constitutive and inducible cyclooxygenases: two enzymes in the spotlight. Biochem. Pharmacol. 65, 153-159   DOI   ScienceOn
36 Rathel, T. R, Leikert, J. F., Vollmar, A. M. and Dirsh, V. M. (2005). The soy isoflavanone genistein induces a late but sustained activation of the endothelial nitric oxide-synthase system in vitro. Br. J. Pharmacol. 144, 394-399   DOI   ScienceOn
37 Rollinger, J. M., Bodensieck, A., Seger, C., Ellmerer, E. P., Bauer, R, Langer, T. and Stappner, H. (2005). Discovering COX-inhibiting constituents of MOTUS root bark: activityguided versus computer-aided methods. Planta Med. 71, 399-405   DOI   ScienceOn
38 Sala, A., Recio, M. C., Giner, R. M., Manez, S. and Rios, J-L. (2000). Anti-phospholipase $A_{2}$ and anti-inflammatory activity of Santolina chamaecyparissus. Life Sci. 66, PL35-40   DOI   ScienceOn
39 Son, D., Lee, P., Lee, J., Kim, H. and Kim, S. Y. (2004). Neuroprotective effect of wogonin in hippocampal slice culture exposed to oxygen and glucose deprivation. Eur. J. Pharmacol. 493, 99-122   DOI   ScienceOn
40 Kowalski, J., Samojedny, A., Paul, M., Pietsz, G. and Wilczak, T. (2005b). Effect of kaempferol on the production and gene expression of monocyte chemoattractant protein-1 in J774.2 macrophages. Pharmacol. Reports 57, 107-112
41 Xagorari, A., Papapetropoulos, A., Mauromatis, A., Economou, M., Fotsis, T. and Roussos, C. (2001). Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine-production in macrophages. J. Pharm. Exp.Ther. 296, 181-187
42 Van Dross, R. T., Hong, X. and Pelling, J. C. (2005). Inhibition of TPA-induced cyclooxygenase-2 (COX-2) expression by apigenin through downregulation of Akt signal transduction in human keratinocytes. Mol. Carcinog. 44, 83-91   DOI   ScienceOn
43 Comalada, M., Camuesco, D., Sierra, S., Ballester, I., Xaus, J., Galvez, J. and Zarzuelo, A. (2005). In vivo quercitrin antiinflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-$\kappa$B pathway. Eur. J. Immunol. 35, 584-592   DOI   ScienceOn
44 Jang, J., Kim, H. P. and Park, H. (2005). Structure and antiinflammatory activity relationships of wogonin derivatives. Arch. Pharm. Res. 28, 877-884   과학기술학회마을   DOI
45 Abate, A., Yang, G., Wong, R. J., Schroder, H., Stevenson, D. K. and Dennery, P. A. (2005). Apigenin decreases hemin-mediated heme oxygenase-l induction. Free Radical Biol. Med. 39, 711-718   DOI   ScienceOn
46 Chen, C-C., Chow, M-P., Huang, W-C., Lin, Y-C. and Chang, Y-J. (2004). Flavonoids inhibit tumor necrosis factor-a-induced up-regulation of intercellular adhesion molecule-l (ICAM-1) in respiratory epithelial cells through activator protein-l and nuclear factor-$\kappa$B: Structure-activity relationships. Mol. Pharmacol. 66, 683-693
47 Chi, Y. S. and Kim, H. P. (2005). Suppression of cyclooxygenase- 2 expression of skin fibroblasts by wogonin, a plant flavone from Scutellaria radix. Prostag. Leukot. Essen. Fatty Acids 72, 59-66   DOI   ScienceOn
48 Osada, M., Imaoka, S. and Funae, Y. (2004). Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF-1$\alpha$ protein. FEBS Lett. 575, 59-63   DOI   ScienceOn
49 Kanno, S., Shouji, A., Tomizawa, A., Hiura, T., Osanai, Y., Ujibe, M., Obara, Y., Nakahata, N. and Ishikawa, M. (2006). Inhibitory effect of naringenin on lipopolysaccharide (LPS)induced endotoxin shock in mice and nitric oxide production in RAW 264.7 macrophages. Life Sci. 78,673-681   DOI   ScienceOn
50 Stangl, V., Lorenz, M., Ludwig, A., Grimbo, N., Guether, C., Sanad, W., Ziemer, S., Martus, P., Baumann, G. and Stangl K. (2005). The flavonoid phloretin suppresses stimulated expression of endothelial adhesion molecules and reduces activation of human platelets. J. Nutr. 135, 172- 178
51 Bagli, E., Stefaniotou, M., Morbidelli, L., Ziche, M., Psillas, K., Murphy, C. and Fotsis, T. (2004). Luteolin inhibits vascular endothelial growth factor-induced angiogenesis; Inhibition of endothelial cell survival and proliferation by targeting phosphatidylinositol 3'-kinase activity. Cancer Res. 64, 7936-7946   DOI   ScienceOn
52 Kim, J. S., Lee, H. J., Lee, M. H., Kim, J., Jin, C. and Ryu, J. H. (2006). Luteolin inhibits LPS-stimulated inducible nitric oxide synthase expression in BY-2 microglial cells. Pianta Med. 72, 65-68   DOI   ScienceOn
53 Njamen, D., Mbafor, J. T., Fomum, Z. T., Kamanyi, A., Mbanya, J-C., Recio, M. C., Giner, R., Manez, S. and Rios, J. L. (2004). Anti-inflammatory activities of two flavanones, sigmoidin A and sigmoidin B, from Erythria sigmoidea. Pianta Med. 70, 104-107   DOI   ScienceOn
54 Park, H., Dao, T. T. and Kim, H. P. (2005). Synthesis and inhibition of $PGE_{2}$ production of 6,8-disubstituted chrysin derivatives. Eur. J. Med. Chem. 40, 943-948   DOI   ScienceOn
55 Tanaka, S., Sato, T., Akimoto, N., Yano, M. and Ito, A. (2004). Prevention of UVB-induced photoinflammation and photoagaing by a polymethoxy flavonoid, nobiletin, in human keratinocytes in vivo and in vitro. Biochem. Pharmacol. 68, 433-439   DOI   ScienceOn
56 Hegde, V. R., Dai, P., Patel, M. G., Puar, M. S., Das, P., Pai, J., Bryant, R. and Cox, P. A. (1997). Phospholipase $A_{2}$ inhibitors from an Erythrina species from Samoa. J. Nat. Prod. 60, 537-539   DOI   ScienceOn
57 O'Leary, K. A., de Pascual-Tereasa, S., Needs, P. W., Bao, Y-P., O'Brien, N. M. and Williamson, G. (2004). Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription. Mut. Res. 551, 245-254   DOI
58 Kim, H. P., Son, K. H., Chang, H. W. and Kang, S. S. (2004). Anti-inflammatory plant flavonoids and cellular action mechanisms. J. Pharmacol. Sci. 96, 229-245   DOI   ScienceOn
59 Han, C. K., Son, M. J., Chang, H. W., Chi, Y. S., Park, H. and Kim, H. P. (2005). Inhibition of prostaglandin production by a structurally optimized flavonoid derivative, 2',4',7-trimethoxyflavone and cellular action mechanism. BioI. Pharm. Bull. 28, 1366-1370   DOI   ScienceOn
60 Nathan, C. (1992). Nitric oxide as a secretory product of mammalian cells. FASEB J. 6, 3051-3064   DOI
61 Rao, Y. K., Fang, S-H. and Tzeng, Y-M. (2005). Inhibitory effects of the flavonoids isolated from Waltheria indica on the production of NO, TNF-$\alpha$ and IL-12 in activated macrophages. BioI. Pharm. Bull. 28,912-915   DOI   ScienceOn
62 de Pascual-Teresa, S., Johnston, K. L., DuPont, M. S., O'Leary, K. A., Needs, P. W., Morgan, L. M., Clifford, M. N., Bao, Y. and Williamson, G. (2004). Quercetin metabolites downregulate cyclooxygenase-2 transcription in human lymphocytes ex vivo but not in vivo. J. Nutr. 134, 552-557