Abstract
Wogonin (5,7-dihydroxy-8-methoxyflavone) is a down-regulator of cyclooxygenase-2 and inducible nitric oxide synthase expression, contributing to anti-inflammatory activityin vivo. For further characterization of modulatory activity on proinflammatory gene expressionin vivo, the effect of wogonin was examined in this experiment using animal models of skin inflammation. By topical application, wogonin inhibited an edematic response as well as proinflammatory gene expression against contact dermatitis in mice. Wogonin inhibited ear edema (19.4-22.6%) at doses of 50–200 μg/ear and down-regulated interleukin-1β induction (23.1%) at 200 μg/ear in phenol-induced simple irritation. Wogonin (2×50-2×200 μg/ear) also inhibited edematic response (51.2-43.9%) and down-regulated proinflammatory gene expression of cyclooxygenase-2, interleukin-1 β, interferon-γ, intercellular adhesion molecule-1 and inducible nitric oxide synthase with some different sensitivity against picryl chloride-induced delayed hypersensitivity reaction. All these results clearly demonstrate that wogonin is a down-regulator of proinflammatory gene expression in animal models of skin inflammation. Therefore, wogonin may have potential for a new anti-inflammatory agent against skin inflammation.
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Chang, Y-L., Shen, J-J., Wung, B-S., Chen, J-J., and Wang, D. L., Chinese herbal remedy wogonin inhibits monocyte chemotactic protein-1 gene expression in human endothelial cells.Mol. Pharmacol., 60, 507–513 (2001).
Chi, Y. S., Cheon, B. S., and Kim, H. P., Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells.Biochem. Pharmacol., 61, 1195–1203 (2001).
Chi, Y. S., Lim, H., Park, H., and Kim, H. P., 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 (2003).
Goppelt-Struebe M., Molecular mechanisms involved in the regulation of prostaglandin biosynthesis by glucocorticoids.Biochem. Pharmacol., 53, 1389–1395 (1997).
Jang, M. and Pezzuto, J. M., Effects of resveratrol on 12-O-tetradecanoylphorbol-13-acetate-induced oxidative events and gene expression in mouse skin.Cancer Lett., 134, 81–89 (1998).
Kim, H. K., Cheon, B. S., Kim, Y. H., Kim, S. Y., and Kim, H. P., Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structural-activity relationships.Biochem. Pharmacol., 58, 759–765 (1999a).
Kotanidou, A., Xagorari, A., Bagli, E., Kitsanta, P., Fotsis, T., Papapetropoulos, A., and Roussos, C., Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice.Am. J. Respir. Crit. Care Med., 165, 818–823 (2002).
Krol, W., Czuba, Z. P., Threadgill, M. D., Cunningham, B. D., and Pietse, G., Inhibition of nitric oxide (NO) production in murine macrophages by flavones.Biochem. Pharmacol., 50, 1031–1035 (1995).
Liang, Y-C., Huang, Y-T., Tsai, S-H., Shiau, S-Y., Chen, C-F., and Lin, J-K., Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages.Carcinogenesis, 20, 1945–1952 (1999).
Lim, B. O., Choue, R. W., Lee, H. Y., Seong, N. S., and Kim, J. D., Effect of the flavonoid components obtained from Scutellaria radix on the histamine, immunoglobulin E and lipid peroxidation of spleen lymphocytes of Sprague-dawley rats.Biosci. Biotechnol. Biochem., 67, 1126–1129 (2003).
Middleton, E., Kandaswami, C., and Theoharides, T. C., The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer.Pharmacol. Rev., 52, 673–751 (2000).
Mitsui, G., Mitsui, K., Hirano, T., Phara, O., Kato, M., and Niwano, Y., Kinetic profiles of sequential gene expressions for chemokines in mice with contact hypersensitivity.Immunol. Lett., 68, 191–197 (2003).
Norris, P., Poston, R. N., Thomas, D. S., Thornhill, M., Hawk, J., and Haskard, D. O., 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 (1991).
Park, B. K., Heo, M. Y., Park, H., and Kim, H. P., Inhibition of TPA-induced cyclooxygenase-2 and skin inflammation in mice by wogonin, a plant flavone from Scutellaria radix.Eur. J. Pharmacol., 425, 153–157 (2001).
Piguet, P. F., Grau, G. E., Hauser, C., and Vassali, P., Tumor necrosis factor is a critical mediator in hapten-induced irritant and contact hypersensitivity reaction.J. Exp. Med., 173, 673–679 (1991).
Raso, G. M., Meli, R., Di Carlo, G., Pacillio, M., and Di Carlo, R., Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids in macrophage J774A.1.Life Sci., 68, 921–931 (2001).
Rietschel, R. L. and Fowler, J. E. {jrJr.} (eds.): Fischer’s contact dermatitis, 4th Ed., Baltimore, Williams & Wilkins, 1995, pp 1–10.
Shomick, L. P., Detogni, P., Mariathasan, S., Goellner, J., Strauss-Schoenberger, J., Karr, R. W., Ferguson, T. A., and Caplin, D. D., Mice deficient in IL-1β manifest impaired contact hypersensitivity to trinitrobenzene.J. Exp. Med., 183, 1427–1436 (1996).
Soliman, K. F. and Mazzio, E. A.,In vitro attenuation of nitric oxide production in C6 astrocyte cell culture by various dietary compounds.Proc. Soc. Exp. Biol. Med., 218, 390–397 (1998).
Takahashi, K., Morikawa, A., Kato, Y., Sugiyama, T., Koide, N., Mu, M. M., Yoshida, T., and Yokochi, T., Flavonoids protect mice from two types of lethal shock induced by endotoxin.FEMS Immunol. Med. Microbiol., 31, 29–33 (2001).
Wadsworth, T., McDonald, T. L., and Koop, D. R., Effects of Ginkgo biloba extract (Egb 761) and quercetin on lipopolysachharide-induced signaling pathway involved in the release of tumor necrosis factor-α.Biochem. Pharmacol., 62, 963–974 (2001).
Wakabayashi, I., Inhibitory effects of baicalein and wogonin on lipopolysaccharide-induced nitric oxide production in macrophages.Pharmacol. Toxicol., 84, 288–291 (1999).
Willis, C. M., Young, E., Brandon, D. R., and Wilkinson, J. D., Immunopathological and ultrastructural findings in human allergic and irritant contact dermatitis.Br. J. Dermatol., 115, 305–316 (1986).
Xagorari, A., Roussos, C., and Papapetropoulos, A., Inhibition of LPS-stimulated pathways in macrophages by the fiavonoid luteolin.Brit. J. Pharmacol., 136, 1058–1064 (2002).
You, K. M., Jong, H., and Kim, H. P., Inhibition of cyclooxygenase/lipoxygenase from human platelets by polyhydroxylated/methoxylated flavonoids isolated from the several medicinal plants.Arch. Pharm. Res., 22, 18–24 (1999).
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Lim, H., Park, H. & Kim, H.P. Inhibition of contact dermatitis in animal models and suppression of proinflammatory gene expression by topically applied Flavonoid, Wogonin. Arch Pharm Res 27, 442–448 (2004). https://doi.org/10.1007/BF02980087
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DOI: https://doi.org/10.1007/BF02980087