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http://dx.doi.org/10.4062/biomolther.2007.15.1.007

Molecular Events on Experimental Skin Inflammation and Modulation by Topical Anti-inflammatory Flavonoids  

Kim, Hyun-Pyo (College of Pharmacy, Kangwon National University)
Publication Information
Biomolecules & Therapeutics / v.15, no.1, 2007 , pp. 7-15 More about this Journal
Abstract
There have been various animal models of skin inflammation. These models have been used for establishing anti-inflammatory activity of the topical agents including cosmetics. Here, the molecular mechanisms of most widely-used animal models of skin inflammation including contact irritation, acute and chronic inflammation, and delayed-type hypersensitivity are summarized. Against these animal models, varieties of plant flavonoids showed anti-inflammatory activity. The action mechanisms of anti-inflammation by topical flavonoids are presented. A therapeutic potential of flavonoids is discussed.
Keywords
skin; inflammation; flavonoid;
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1 Nickoloft, B. J., Griffiths, C. E. M. and Barker, J. N. W. N. (1990). The role of adhesion molecules, chemotactic factors, and cytokines in inflammatory and neoplastic skin disease-1990 update. J. Invest. Dermatol. 94, 151S-157S   DOI   ScienceOn
2 Hertog, M. G. L., Hollman, P. C. H. and Katan, M. B. (1992). Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands. J. Agri. Food Chem. 40, 2379-2383   DOI
3 Manach, C., Williamson, G., Morand, C., Scalbert, A. and Remesy, C. (2005). Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr. 81(Suppl.), 230S-242S   DOI
4 Li, B. and Birt, D. F. (1996). In vivo and in vitro percutaneous absorption of cancer preventive flavonoid apigenin in different vehicles in mouse skin. Pharmaceutical Res. 13, 1710-1715   DOI
5 Kuhnau J. (1976). The flavonoids: A class of semi-essential food components: their role in human nutrition. World Rev. Nutr. Diet 24, 117-191
6 Kwak, W-J., Han, C. K., Son, K. H., Chang, H. W., Kang, S. S., Park, B. K. and Kim, H. P. (2002). Effect of ginkgetin from Ginkgo biloba leaves on cyclooxygenases and in vivo skin inflammation. Planta Med. 68, 316-321   DOI   ScienceOn
7 Lee, S. J., Son, K. H., Chang, H. W., Do, J. C., Jung, K. Y., Kang, S. S. and Kim, H. P. (1993). Anti-inflammatory activity of naturally occurring flavones and flavonol glycosides. Arch. Pharm. Res. 16, 25-28   DOI
8 Lim, H., Park, H. and Kim, H. P. (2004). Inhibition of contact dermatitis in animal models and suppression of proinflammatory gene expression by topically applied flavonoid, wogonin. Arch. Pharm. Res. 27, 442-448   DOI   ScienceOn
9 Lim, H., Son, K. H., Chang, H. W., Kang, S. S. and Kim, H. P. (2006a). Inhibition of chronic skin inflammation by topical anti-inflammatory flavonoid preparation, Ato $Formular^\circledR$. Arch. Pharm. Res. 29, 503-507   과학기술학회마을   DOI   ScienceOn
10 Lim, H., Son, K. H., Chang, H. W., Kang, S. S. and Kim, H. P. (2006b). Effects of anti-inflammatory biflavonoid, ginkgetin, on chronic skin inflammation. Biol. Pharm. Bull. 29, 1046-1049   DOI   ScienceOn
11 Raick, A. N. (1973). Ultrastructural, histological and biochemical alterations produced by 12-O-tetradecanoylphorbol-13-acetate on mouse epidermis and their relevance to skin tumor promotion. Cancer Res. 33, 269-286
12 Moon, J-H., Tsushida, T., Nakahara, K. and Terao, J. (2001). Identification of quercetin 3-O-$\beta$-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin. Free Radic. Biol. Med. 30, 1274-1285   DOI   ScienceOn
13 Manach, C. and Donovan, J. (2004). Pharmacokinetics and metabolism of dietary flavonoids in human. Free Radical Res. 38, 771-185   DOI   ScienceOn
14 Mitsui, G., Mitsui, K., Hirano, T., Ohara, O., Kato, M. and Niwano, Y. (2003). Kinetic profiles of sequential gene expressions for chemokines in mice with contact hypersensitivity. Immunol. Lett. 68, 191-197   DOI   ScienceOn
15 Mizutani, H., Yamanaka, K., Konishi, H. and Murakami, T. (2003). Animal models of psoriasis and pustular psoriasis. Arch. Dermatol. Res. 295, S67-S68   DOI
16 Morita, H., Hori, M. and Kitano, Y. (1996). Modulation of picryl chloride-induced contact hypersensitivity reaction in mice by nitric oxide. J. Invest. Dermatol. 107, 549-552   DOI   ScienceOn
17 Murakami, A., Nakamura, Y., Torikai, K., Tanaka, T., Koshiba, T., Koshimizu, K., Kuwahara, S., Takahashi, Y., Ogawa, K., Yano, M., Tokuda, H., Nishino, H., Mimaki, Y., Sashida, Y., Kitanaka, S. and Ohigashi, H. (2000). Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res. 60, 5059-5066
18 Murakami, M., Yoshihara, K., Shimbara, S., Lambeau, G., Singer, A., Gelb, M. H., Sawada, M., Inagaki, N., Nagai, H. and Kudo, I. (2002). Arachidonate release and eicosanoid generation by group IIE phospholipase $A_2$. Biochem. Biophys. Res. Comm. 292, 689-696   DOI   ScienceOn
19 Norris, P., Poston, R. N., Thomas, D. S., Thorhill, M., Hawk, J. and Haskard, D. O. (1991). The expression of endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in experimental cutaneous inflammation: A comparison of ultraviolet B erythema and delayed hypersensitivity. J. Invest. Dermatol. 96, 763-770   DOI   ScienceOn
20 Stanley, P. L., Steiner, S., Havens, M. and Tramposch, K. M. (1991). Mouse skin inflammation induced by multiple topical application of 12-O-tetradecanoylphorbol-13-acetate. Skin Pharmacol. 4, 262-271   DOI
21 Opas, E. E., Bonney, R. J. and Humes, J. L. (1985). Prostaglandin and leukotriene synthesis in mouse ears inflamed by arachidonic acid. J. Invest. Dermatol. 84, 253-256   DOI   ScienceOn
22 Paganga, G. and Rice-Evans, C. A. (1997). The identification of flavonoids as glucosides in human plasma. FEBS Lett. 401, 78-82   DOI   ScienceOn
23 Park, B. K., Heo, M. Y., Park, H. and Kim, H. P. (2001). Inhibition of TPA-induced cyclooxygenase-2 expression and skin inflammation in mice by wogonin, a plant flavone from Scutellaria radix. Eur. J. Pharmacol. 425, 153-157   DOI   ScienceOn
24 Piguet, P. F., Grau, G. E., Hauser, C. and Vassali, P. (1991). Tumor necrosis factor is a critical mediator in hapten-induced irritant and contact hypersensitivity reactions. J. Exp. Med. 173, 673-679   DOI   ScienceOn
25 Raederstorff, D., Pantze, M., Bachmann, H. and Moser, U. (1996). Anti-inflammatory properties of docosahexaenoic and eicosapentaenoic acids in phorbol-ester-induced mouse ear inflammation. Int. Arch. Allergy Immunol. 111, 284-290   DOI   ScienceOn
26 Sanchez, T. and Moreno, J. J. (1999b). Role of leukocyte influx in tissue prostaglandin-H synthase-2 overexpression induced by phorbol ester and arachidonic acid in skin. Biochem. Pharmacol. 58, 877-879   DOI   ScienceOn
27 Reynolds, N. J., McCombie, S. W., Shankar, B. B., Bishop, W. R. and Fisher, G. J. (1997). SCH 47112, a novel staurosporine derivative, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and epidermal hyperplasia in hairless mouse skin. Arch. Dermatol. Res. 289, 540-546   DOI
28 Ross, J. A. and Kasum, C. M. (2002). Dietary flavonoids: Bioavailability, metabolic effects and safety. Ann. Rev. Nutr. 22, 19-34   DOI   ScienceOn
29 Sanchez, T. and Moreno, J. J. (1999a). Role of prostaglandin H synthase isoforms in murine ear edema induced by phorbol ester application on skin. Prostag. Other Lipid Mediat. 57, 119-131   DOI   ScienceOn
30 Schlingemann, J., Hess, J., Wrobel, G., Breitenbach, U., Gebhardt, C., Steinlein, P., Kramer, H., Furstenberger, G., Hahn, M., Angel, P. and Lichter, P. (2003). Profile of gene expression involved by the tumor promoter TPA in murine epithelial cells. Int. J. Cancer 104, 699-708   DOI   ScienceOn
31 Schon, M. P. (1999). Animal models of psoriasis - What can we learn from them?. J. Invest. Dermatol. 112, 405-410   DOI   ScienceOn
32 Shornick, L. P., De Togni, P., Mariathasan, S., Goellner, J., Strauss-Schoenberger, J., Karr, R. W., Ferguson, T. A. and Chaplin, D. D. (1996). Mice deficient in IL-1$\beta$ manifest impaired contact hypersensitivity to trinitrochlorobenzene. J. Exp. Med. 183, 1427-1436   DOI   ScienceOn
33 Walle, T., Otake, Y., Brubaker, J. A., Walle, U. K. and Halushka, P. V. (2001). Disposition and metabolism of the flavonoid chrysin in normal volunteers. Br. J. Clin. Pharmacol. 51, 143-146   DOI   ScienceOn
34 Tarayre, J. P., Barbara, M., Aliaga, M. and Tsne-Versailles, J. (1990). Comparative actions of immunosuppressants, glucocorticoids and non-steroidal anti-inflammatory drugs on various models of delayed hypersensitivity and in a non-immune inflammation in mice. Arzneim. Forsch. 40, 1125-1131
35 Teixeira, M. M., Williams, T. J. and Hellewell, P. G. (1993). Role of prostaglandins and nitric oxide in acute inflammatory reactions in guinea-pig skin. Br. J. Pharmacol. 110, 1515-1521   DOI   ScienceOn
36 Tsuji, F., Miyake, Y., Horiuchi, M. and Mita, S. (1998). Involvement of leukotriene $B_4$ in murine dermatitis models. Biochem. Pharmacol. 55, 297-304   DOI   ScienceOn
37 Wang, H. Q. and Smart, R. C. (1999). Overexpression of protein kinase C$\alpha$ in the epidermis of transgenic mice results in striking alterations in phorbol ester-induced inflammation and COX-2, MIP-2 and TNF-$\alpha$ expression but not tumor promotion. J. Cell Sci. 112 (Pt 20), 3497-3506
38 Wedmore, C. V. and Williams, T. J. (1981). Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature 289, 646-650   DOI   ScienceOn
39 Wille, J. J., Kydonieus, A. F. and Kalish, R. S. (1998). Inhibition of irritation and contact hypersensitivity by ethacrynic acid. Skin Pharmacol. Appl. Skin Physiol. 11, 279-288   DOI   ScienceOn
40 Williamson, G. and Manach, C. (2005). Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am. J. Clin. Nutr. 81(Suppl.), 243S-255S   DOI
41 Young, J. M., Spires, D. A., Bedord, C. J., Wagner, B., Ballaron, S. J. and De Young, L. M. (1984). The mouse ear inflammatory response to topical arachidonic acid. J. Invest. Dermatol. 82, 367-371   DOI   ScienceOn
42 Yamamoto, S., Aizu, E., Jiang, H., Nakadate, T., Kiyoto, I., Wang, J. C. and Kato, K. (1991). The potent anti-tumor promoting agent isoliquiritigenin. Carcinogenesis 12, 317-323   DOI   ScienceOn
43 Yasukawa, K., Takido, M., Takeuchi, M. and Nakagawa, S. (1989). Effect of chemical constituents from plants on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. Chem. Pharm. Bull. 37, 1071-1073   DOI   ScienceOn
44 Yoshizawa, S., Suganuma, M., Fugiki, H., Fukai, T., Nomura, T. and Sigimura, T. (1989). Morusin, isolated from root bark of Morus alba L., inhibits tumor promotion of teleocidin. Phytotherapy Res. 3, 193-195   DOI
45 Alford, J. G., Stanley, P. L., Todderud, G. and Tramposch, K. M. (1992). Temporal alteration of leukocyte subsets into mouse skin inflamed with phorbol ester. Agents Actions 37, 261-267
46 Wittig, J., Herderich, M., Graefe, E. U. and Veit, M. J. (2001). Identification of quercetin glucuronides in human plasma by high-performance liquid chromatography-tandem mass spectrometry. Chromatography B Biomed. Sci. Appl. 753, 237-243   DOI   ScienceOn
47 Chang, J., Carlson, R. P., Oneill-Davis, L., Lamb, B., Sharma, R. N. and Lewis, A. J. (1986). Correlation between mouse skin inflammation induced by arachidonic acid and eicosanoid synthesis. Inflammation 10, 205-214   DOI
48 Chen, X., Yin, O. Q., Zuo, Z. and Chow, M. S. (2005). Pharmacokinetics and modeling of quercetin and metabolites. Pharm. Res. 22, 892-901   DOI
49 Della Loggia, R., Ragazzi, E., Tubaro, A., Fassina, G. and Vertua R. (1988). Anti-inflammatory activity of benzopyrones that are inhibitors of cyclo- and lipo-oxygenase. Pharmacol. Res. Comm. 20 (Suppl. V), 91-94
50 Adlercreutz, H., Markkanen, H. and Watanabe, S. (1993). Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 342, 1209-1210   DOI   ScienceOn
51 Bouclier, M., Cavey, D., Kail, N. and Hensby, C. (1990). Experimental models in skin pharmacology. Pharmacol. Rev. 42, 127-153
52 Burke, J. R. (2001). Targeting phospholipase A2 for the treatment of inflammatory skin diseases. Curr. Opin. Investig. Drugs 2, 1549-1552
53 Gil, B., Sanz, M. J., Terencio, M. C., Ferrandiz, M. L., Bustos, G., Paya, M., Gunasegaran, R. and Alcaraz, M. J. (1994). Effects of flavonoids on Naja naja and human recombinant synovial phospholipase A2 and inflammatory responses in mice. Life Sci. 54, PL333-338   DOI   ScienceOn
54 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. Essent. Fatty Acids 72, 59-66   DOI   ScienceOn
55 Cheon, B. S., Kim, Y. H., Son, K. H., 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
56 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 induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells. Biochem. Pharmacol. 61, 1195-1203   DOI   ScienceOn
57 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: Cyclooxygenases and lipoxygenases. Biochem. Pharmacol. 62, 1185-1191   DOI   ScienceOn
58 Chi, Y. S., Lim, H., Park, H. and Kim, H. P. (2003). Effect of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression. Biochem. Pharmacol. 66, 1271-1278   DOI   ScienceOn
59 Day, A. J., Mellon, F., Barron, D., Sarrazin, G., Morgan, M. R. and Williamson, G. (2001). Human metabolism of dietary flavonoids: identification of plasma metabolites of quercetin. Free Radic. Res. 35, 941-952   DOI   ScienceOn
60 Kennard, M. D, Kang, D. C., Montgomery, R. L. and Butler, A. P. (1995). Expression of epidermal ornithine decarboxylase and nuclear proto-oncogene in phorbol ester tumor promotor-sensitive and -resistant mice. Mol. Carcinog. 12, 14-22   DOI   ScienceOn
61 Erlund, I., Kosonen, T., Alfthan, G., Maenpaa, J., Perttunen, K., Kenraali, J., Parantainen, J. and Aro, A. (2000). Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur. J. Clin. Pharmacol. 56, 545-553   DOI   ScienceOn
62 Della Loggia, R., Tubaro, A., Dri, P., Zilli, C. and Del Negro, P. (1986). The role of flavonoids in the anti-inflammatory activity of Chamomilla recutita. In Plant flavonoids in biology and medicines, 1986 (Cody et al. Eds.), pp. 481-484. Alan R. Liss, New York
63 De Young, L. M., Kheifets, J. B., Ballaron, S. J. and Young, J. M. (1989). Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially modulated by pharmacologic agents. Agents Actions 26, 335-341   DOI
64 Enk, A. H. and Katz, S. J. (1992). Early molecular events in the induction phase of contact sensitivity. Proc. Nat'l. Acad. Sci. USA 89, 1398-1402   DOI   ScienceOn
65 Fogh, K. and Kragballe, K. (2000). Eicosanoids in inflammatory skin diseases. Prostag. Other Lipid Mediat. 63, 43-54   DOI   ScienceOn
66 Fuchs, J. and Milbradt, R. (1993). Skin anti-inflammatory activity of apigenin-7-glucoside in rats. Arzneim. Forsch. 43, 370-372
67 Fujii, E., Irie, K., Uchida, Y., Ohba, K. and Muraki, T. (1995). Role of eicosanoids but not nitric oxide in the platelet-activating factor-induced increase in vascular permeability in mouse skin. Eur. J. Pharmacol. 273, 267-272   DOI   ScienceOn
68 Kubo, M., Matsuda, H., Tanaka, M., Kimura, Y., Okuda, H., Higashino, M., Tani, T., Namba, K. and Arichi, S. (1984). Studies on Scutellaria radix. VII. Anti-arthritic and anti-inflammatory actions of methanolic extract and flavonoid components from Scutellaria radix. Chem. Pharm. Bull. 32, 2724-2729   DOI   ScienceOn
69 Hollman, P. C. H., van Trijp, J. M. P., Mengelers, M. J. B., de Vries, J. H. M. and Katan, M. B. (1997). Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Lett. 114, 139-140   DOI   ScienceOn
70 Hara, H., Sukamoto, T., Ohtaka, H., Abe, K., Tatumi, Y., Saito, Y., Suzuki, A. and Tsukamoto, G. (1992). Effects of baicalein and $\alpha$-tocopherol on lipid peroxidation, free radical scavenging activity and 12-O-tetradecanoylphorbol acetate-induced ear edema. Eur. J. Pharmacol. 221, 193-198   DOI   ScienceOn
71 Hsiu, S. L., Huang, T. Y., Hou, Y. C., Chin, D. H. and Chao, P. D. (2002). Comparison of metabolic pharmacokinetics of naringin and naringenin in rabbits. Life Sci. 70, 1481-1489   DOI   ScienceOn
72 Inoue, H., Mori, T. and Koshihara, Y. (1988). Sulfidopeptide-leukotrienes are major mediators of arachidonic acid-induced mouse ear edema. Prostaglandins 36, 731-739   DOI   ScienceOn
73 Iversen, L. and Kragballe, K. (2000). Arachidonic acid metabolism in skin health and disease. Prostag. Other Lipid Mediat. 63, 25-42   DOI   ScienceOn
74 Jang, M. and Pezzuto, J. M. (1998). Effects of resveratrol on 12-O-tetradecanoylphorbol-13-acetate-induced oxidative events and gene expression in mouse skin. Cancer Lett. 134, 81-89   DOI   ScienceOn
75 Kato, R., Nakadate, T., Yamamoto, S. and Sugimura, T. (1983). Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion and ornithine decarboxylase activity by quercetin: possible involvement of lipoxygenase inhibition. Carcinogenesis 4, 1301-1305   DOI   ScienceOn
76 Maldve, R. E., Kim, Y., Muga, S. J. and Fisher, S. M. (2000). Prostaglandin E2 regulation of cyclooxygenase expression in keratinocytes is mediated via cyclic nucleotide-linked prostaglandin receptors. J. Lipd Res. 41, 873-881
77 Kim, H. K., Namgoong, S. Y. and Kim, H. P. (1993). Antiinflammatory activity of flavonoids: Mice ear edema inhibition. Arch. Pharm. Res. 16, 18-24   DOI
78 Kim, D. W., Chi, Y. S., Son, K. H., Chang, H. W., Kim, J. S., Kang, S. S. and Kim, H. P. (2002). Effects of sophoraflavanone G, a prenylated flavonoid from Sophora flavescens on cyclooxygenase-2 and in vivo inflammatory response. Arch. Pharm. Res. 25, 329-335   DOI   ScienceOn
79 Kim, H., Kim, Y. S., Kim, S. Y. and Suk, K. (2001). The plant flavonoid wogonin suppresses death of activated C6 rat glial cells by inhibiting nitric oxide production. Neurosci. Lett. 309, 67-71   DOI   ScienceOn
80 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
81 Kim, H. K., Son, K. H., Chang, H. W., Kang, S. S. and Kim, H. P. (1998a). Amentoflavone, a plant biflavone: A new potential anti-inflammatory agent. Arch. Pharm. Res. 21, 406-410   DOI   ScienceOn
82 Kim, H. P., Mani, I., Iversen, L. and Ziboh, V. A. (1998b). Effects of naturally occurring flavonoids and biflavonoids on epidermal cyclooxygenase and lipoxygenase from guinea-pigs. Prostag. Leukot. Essent. Fatty Acids 58, 17-24   DOI   ScienceOn
83 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
84 Murota, K. and Terao, J. (2003). Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism. Arch. Biochem. Biophys. 417, 12-17   DOI   ScienceOn