The present work aimed to assess novel pharmacological properties of ethyl vanillin (EVA) which is used as a flavoring agent for cakes, dessert, confectionary, etc. EVA exhibited an inhibitory activity in the chorioallantoic membrane angiogenesis. Anti-inflammatory activity of EVA was convinced using the two in vivo models, such as vascular permeability and air pouch models in mice. Antinociceptive activity of EVA was assessed using acetic acid-induced writhing model in mice. EVA suppressed production of nitric oxide and induction of inducible nitric oxide synthase in the lipopolysaccharide (LPS)-activated RAW264.7 macrophage cells. However, EVA could not suppress induction of cyclooxygenase-2 in the LPS-activated macrophages. EVA diminished reactive oxygen species level in the LPS-activated macrophages. EVA also suppressed enhanced matrix metalloproteinase-9 gelatinolytic activity in the LPSactivated RAW264.7 macrophage cells. EVA at the used concentrations couldn’t diminish viability of the macrophage cells. Taken together, the anti-angiogenic, anti-inflammatory and anti-nociceptive properties of EVA are based on its suppressive effect on the production of nitric oxide possibly via decreasing the reactive oxygen species level.
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Bubici, C., Papa, S., Dean, K., and Franzoso, G., Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance. Oncogene, 25, 6731–6748 (2006).
Cuzzocrea, S., Role of nitric oxide and reactive oxygen species in arthritis. Curr. Pharm. Des., 12, 3551–3570 (2006).
Freshney, R. I., Culture of animal cells: a manual of basic technique. 4th ed. Wiley-Liss Press, New York, pp. 336–338, (1994).
Ghosh, A. K., Hirasawa, N., Niki, H., and Ohuchi, K., Cyclooxygenase-2-mediated angiogenesis in carrageenan-induced granulation tissue in rats. J. Pharmacol. Exp. Ther., 295, 802–809 (2000).
Griffioen, A. W. and Molema, G., Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol. Rev., 52, 237–268 (2000).
Gustafson, D. L., Franz, H. R., Ueno, A. M., Smith, C. J., Doolittle, D. J., and Walden, C. A., Vanillin (3-methoxy-4-hydroxybenzaldehyde) inhibits mutation induced by hydrogen peroxide, N-methyl-N-nitrosoguanidine and mitomycin C but not 137Cs gamma radiation at the CD59 locus in human-hamster hybrid A(L) cells. Mutagenesis, 15, 207–213 (2000).
Ingber, D., Fujita, T., Kishimoto, S., Sudo, K., Kanamaru, T., Brem, H., and Folkman, J., Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature, 348, 555–557 (1990).
Iurlaro, M., Benelli, R., Masiello, L., Rosso, M., Santi, L., and Albini, A., Beta interferon inhibits HIV-1 Tat-induced angiogenesis: synergism with 13-cis retinoic acid. Eur. J. Cancer, 34, 570–576 (1998).
Kamat, J. P., Ghosh, A., and Devasagayam, T. P. A., Vanillin as an antioxidant in rat lever mitochondria: Inhibition of protein oxidation and lipid peroxidation induced by photosensitization. Mol. Cell. Biochem., 209, 47–53 (2000).
Kleiner, D. E. and Stetler-Stevenson, W. G., Quantitative zymography: detection of picogram quantities of gelatinases. Anal. Biochem., 218, 325–329 (1994).
Kumar, S. S., Priyadarsini, K. I., and Sainis, K. B., Inhibition of peroxynitrite-mediated reactions by vanillin. J. Agric. Food Chem., 52, 139–145 (2004).
Lee, J. Y., Jang, Y. W., Kang, H. S., Moon, H., Sim, S. S., and Kim, C.-J., Anti-inflammatory action of phenolic compounds from Gastrodia elata root. Arch. Pharm. Res., 29, 849–858 (2006).
Lim, E. J., Kang, H. J., Jung, H. J., and Park, E. H., Antiangiogenic, anti-inflammatory and anti-nociceptive activity of 4-hydroxybenzyl alcohol. J. Pharm. Pharmacol., 59, 1235–1240 (2007).
Lirdprapamongkol, K., Sakurai, H., Kawasaki, N., Choo, M. K., Saitoh, Y., Aozuka, Y., Singhirunnusorn, P., Ruchirawat, S., Svasti, J., and Saiki, I., Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast cancer cells. Eur. J. Pharm. Sci., 25, 57–65 (2005).
Mamer, O. A., Montgomery, J. A., Deckelbaum, R. J., and Granot, E., Identification of urinary 3-ethoxy-4-hydroxybenzoic and 3-ethoxy-4-hydroxymandelic acids after dietary intake of ethyl vanillin. Biomed. Mass Spectrom., 12, 163–169 (1985).
Mott, J. D. and Werb, Z., Regulation of matrix biology by matrix metalloproteinases. Curr. Opin. Cell Biol., 16, 558–564 (2004).
Nordberg, J. and Arner, E. S., Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic. Biol. Med., 31, 1287–1312 (2001).
Ojemann, L. M., Nelson, W. L., Shin, D. S., Rowe, A. O., and Buchanan, R. A., Tien ma, an ancient Chinese herb, offers new options for the treatment of epilepsy and other conditions. Epilepsy Behav., 8, 376–383 (2006).
Olajide, O. A., Awe, S. O., Makinde, J. M., Ekhelar, A. I., Olusola, A., Morebise, O., and Okpako, D. T., Studies on the anti-inflammatory, antipyretic and analgesic properties of Alstonia boonei stem bark. J. Ethnopharmacol., 71, 179–186 (2000).
Royall, J. A. and Ischiropoulos, H., Evaluation of 2′,7′-dichlorofluorescin and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells. Arch. Biochem. Biophys., 302, 348–355 (1993).
Sherman, M. P., Aeberhard, E. E., Wong, V. Z., Griscavage, J. M., and Ignarro, L. J., Pyrrolidine dithiocarbamate inhibits induction of nitric oxide synthase activity in rat alveolar macrophages. Biochem. Biophys. Res. Commun., 191, 1301–1308 (1993).
Singh, V. K., Mehrotra, S., Narayan, P., Pandey, C. M., and Agarwal, S. S., Modulation of autoimmune diseases by nitric oxide. Immunol. Res., 22, 1–19 (2000).
Song, Y. S., Kim, S. H., Sa, J. H., Jin, C., Lim, C. J., and Park, E. H., Anti-angiogenic and inhibitory activity on inducible nitric oxide production of the mushroom Ganoderma lucidum. J. Ethnopharmacol., 90, 17–20 (2004).
Sorsa, T., Tjäderhane, L., Konttinen, Y. T., Lauhio, A., Salo, T., Lee, H.-M., Golub, L. M., Brown, D. L., and Mäntylä, P., Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann. Med., 38, 306–321 (2006).
Tamargo, R. J., Bok, R. A., and Brem, H., Angiogenesis inhibition by minocycline. Cancer Res., 51, 672–675 (1991).
Tong, Y., Zhang, X., Zhao, W., Zhang, Y., Lang, J., Shi, Y., Tan, W., Li, M., Zhang, Y., Tong, L., Lu, H., Lin, L., and Ding, J., Anti-angiogenic effects of shiraiachrome A, a compound isolated from a Chinese folk medicine used to treat rheumatoid arthritis. Eur. J. Pharmacol., 494, 101–109 (2004).
Vogel, H. G. and Vogel, W. H., Drug Discovery and Evaluations, Pharmacological Assays. Springer, Berlin, pp. 402–403, (1997).
Whittle, B. A., The use of changes in capillary permeability in mice to distinguish between narcotic and nonnarcotic analgesics. Br. J. Pharmacol. Chemother., 22, 246–253 (1964).
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Jung, HJ., Song, Y.S., Kim, K. et al. Assessment of the anti-angiogenic, anti-inflammatory and antinociceptive properties of ethyl vanillin. Arch. Pharm. Res. 33, 309–316 (2010). https://doi.org/10.1007/s12272-010-0217-2
- Ethyl vanillin
- Nitric oxide
- Reactive oxygen species