Abstract
Wogonin (5,7-dihydroxy-8-methoxyflavone) has been reported to exhibit a variety of biological properties including anti-inflammatory and neuroprotective functions. In this study, biological activities of diverse synthetic wogonin derivatives have been evaluated in two experimental cell culture models. Inhibitory activities of wogonin derivatives on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells and on hydrogen peroxide (H202)-induced neuronal cell death in SH-SY5Y human neuroblastoma were examined. Wogonin derivatives such as WS2 and WS3 showed more potent suppressive activities on LPS-induced NO production and H202-induced cytotoxicity than wogonin itself. In addition, thiol substitution played a minor role in enhancing the activities of the derivatives. These findings may contribute to the development of novel anti-inflammatory and neuroprotective agents derived from wogonin.
Similar content being viewed by others
References
Blasi, E., Barluzzi, R., Bocchini, V., Mazzolla, R., and Bistoni, F., Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus.J. Neuroimmunol., 27,229–237 (1990).
Chandra, J., Samali, A., and Orrenius, S., Triggering and modulation of apoptosis by oxidative stress.Free Radic Biol. Med., 29, 323–333 (2000).
Chen, Y. C., Shen, S. C., Chen, L. G., Lee, T. J., and Yang, L. L., Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors and lipopolysaccharide.Biochem. Pharmacol., 61,1417–1427 (2001).
Cho, J. and Lee, H. K., Wogonin inhibits excitotoxic and oxidative neuronal damage in primary cultured rat cortical cells.Eur. J. Pharmacol., 485,105–110 (2004).
Dao, T. T., Chi, Y. S., Kim, J., Kim, H. P., Kim, S., and Park, H., Synthesis and inhibitory activity against COX-2 catalyzed prostaglandin production of chrysin derivatives.Bioorg Med. Chem. Lett., 14,1165–1167 (2004a).
Dao, T. T., Kim, S. B., Sin, K. S., Kim, S., Kim, H. P., and Park, H., Synthesis and biological activities of 8-arylflavones.Arch. Pharm. Res., 27,278–282 (2004b).
Gao, Z., Huang, K., and Xu, H., Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells.Pharmacol. Res., 43,173–178 (2001).
Gao, Z., Huang, K., Yang, X., and Xu, H., Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi.Biochim. Biophys. Acta, 1472,643–650 (1999).
Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S., and Tannenbaum, S. R., Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids.Anal. Biochem., 126,131–138(1982).
Kang, S. S., Lee, J. Y., Choi, Y. K., Kim, G. S., and Han, B. H., Neuroprotective effects of flavones on hydrogen peroxide-induced apoptosis in SH-SY5Y neuroblostoma cells.Bioorg. Med. Chem. Lett., 14,2261–2264 (2004).
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 structure-activity relationships.Biochem. Pharmacol., 58, 759–765(1999).
Kim, S. S., Kong, P. J., Kim, B. S., Sheen, D. H., Nam, S. Y., and Chun, W., Inhibitory action of minocycline on lipopoly-saccharide-induced release of nitric oxide and prostaglandin E2 in BV2 microglial cells.Arch. Pharm. Res., 27, 314–318 (2004).
Lee, H., Kim, Y. O., Kim, H., Kim, S. Y., Noh, H. S., Kang, S. S., Cho, G. J., Choi, W. S., and Suk, K., Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia.Faseb. J., 17,1943–1944 (2003).
Liu, B., Gao, H. M., Wang, J. Y., Jeohn, G. H., Cooper, C. L., and Hong, J. S., Role of nitric oxide in inflammation-mediated neurodegeneration.Ann. N. Y. Acad. Sci., 962, 318–331 (2002).
Middleton, E., Jr., 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).
Murphy, M. P., Nitric oxide and cell death.Biochim. Biophys. Acta., 1411,401–414(1999).
Simonian, N. A. and Coyle, J. T., Oxidative stress in neurodegenerative diseases.Annu. Rev. Pharmacol. Toxicol., 36, 83–106(1996).
Wakabayashi, I. and Yasui, K., Wogonin inhibits inducible prostaglandin E(2) production in macrophages.Eur. J. Pharmacol., 406,477–481 (2000).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chun, W., Lee, H.J., Kong, PJ. et al. Synthetic wogonin derivatives suppress lipopolysaccharide-induced nitric oxide production and hydrogen peroxide-induced cytotoxicity. Arch Pharm Res 28, 216–219 (2005). https://doi.org/10.1007/BF02977718
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02977718