Abstract
Visnagin, which is found in Ammi visnaga, has biological activity as a vasodilator and reduces blood pressure by inhibiting calcium influx into the cell. The present study demonstrates the anti-inflammatory effect of visnagin on lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. When cells were treated with visnagin prior to LPS stimulation, production of nitric oxide and expression of iNOS were attenuated in a dose-dependent manner. Visnagin also caused a significant decrease of mRNA expression and release of TNF-α, IL-1β and IFNγ. In addition, visnagin reduced LPS-induced IL-6 and MCP-1 mRNA level. We further found that visnagin dose-dependently inhibited LPS-induced AP-1 and NF-κB luciferase activities. Taken together, our results for the first time suggest that the anti-inflammatory effect of visnagin might result from the inhibition of transcription factors, such as AP-1 and NF-κB.
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Aquilano, K., Baldelli, S., Rotilio, G., and Ciriolo, M. R., Role of nitric oxide synthases in Parkinson’s disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem. Res., 33, 2416–2426 (2008).
Bae, E. A., Kim, E. J., Park, J. S., Kim, H. S., Ryu, J. H., and Kim, D. H., Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferon-gamma-stimulated BV-2 microglial cells. Planta Med., 72, 627–633 (2006).
Candelario-Jalil, E., De Oliveira, A. C., Graf, S., Bhatia, H. S., Hull, M., Munoz, E., and Fiebich, B. L., Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J. Neuroinflammation, 4, 25 (2007).
Chen, J. C., Ho, F. M., Pei-Dawn Lee, C., Chen, C. P., Jeng, K. C., Hsu, H. B., Lee, S. T., Wen Tung, W., and Lin, W. W., Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IkappaB kinase, nuclear factorkappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia. Eur. J. Pharmacol., 521, 9–20 (2005).
Chu, S. C., Marks-Konczalik, J., Wu, H. P., Banks, T. C., and Moss, J., Analysis of the cytokine-stimulated human inducible nitric oxide synthase (iNOS) gene: characterization of differences between human and mouse iNOS promoters. Biochem. Biophys. Res. Commun., 248, 871–878 (1998).
De Simone, R., Levi, G., and Aloisi, F., Interferon gamma gene expression in rat central nervous system glial cells. Cytokine, 10, 418–422 (1998).
Duarte, J., Perez-Vizcaino, F., Torres, A. I., Zarzuelo, A., Jimenez, J., and Tamargo, J., Vasodilator effects of visnagin in isolated rat vascular smooth muscle. Eur. J. Pharmacol., 286, 115–122 (1995).
Duarte, J., Torres, A. I., and Zarzuelo, A., Cardiovascular effects of visnagin on rats. Planta Med., 66, 35–39 (2000).
Faggioli, L., Costanzo, C., Donadelli, M., and Palmieri, M., Activation of the Interleukin-6 promoter by a dominant negative mutant of c-Jun. Biochim. Biophys. Acta, 1692, 17–24 (2004).
Graeber, M. B. and Streit, W. J., Microglia: biology and pathology. Acta Neuropathol., 119, 89–105 (2010).
Jang, S., Kelley, K. W., and Johnson, R. W., Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc. Natl. Acad. Sci. U.S.A., 105, 7534–7539 (2008).
Jung, J. S., Yan, J. J., and Song, D. K., Protective effect of decursinol on mouse models of sepsis: enhancement of interleukin-10. Korean J. Physiol. Pharmacol., 12, 79–81 (2008).
Kao, T. K., Ou, Y. C., Raung, S. L., Lai, C. Y., Liao, S. L., and Chen, C. J., Inhibition of nitric oxide production by quercetin in endotoxin/cytokine-stimulated microglia. Life Sci., 86, 315–321 (2010).
Kaul, B. and Staba, E. J., Visnagin: biosynthesis and isolation from Ammi visnagi suspension cultures. Science, 150, 1731–1732 (1965).
Kawanokuchi, J., Mizuno, T., Takeuchi, H., Kato, H., Wang, J., Mitsuma, N., and Suzumura, A., Production of interferon-gamma by microglia. Mult. Scler., 12, 558–564 (2006).
Lee, C. J., Lee, S. S., Chen, S. C., Ho, F. M., and Lin, W. W., Oregonin inhibits lipopolysaccharide-induced iNOS gene transcription and upregulates HO-1 expression in macrophages and microglia. Br. J. Pharmacol., 146, 378–388 (2005).
Lu, D. Y., Tang, C. H., Chen, Y. H., and Wei, I. H., Berberine suppresses neuroinflammatory responses through AMP-activated protein kinase activation in BV-2 microglia. J. Cell. Biochem., 110, 697–705 (2010).
Park, S. H., Kang, J. S., Yoon, Y. D., Lee, K., Kim, K. J., Lee, K. H., Lee, C. W., Moon, E. Y., Han, S. B., Kim, B. H., Kim, H. M., and Park, S. K., Glabridin inhibits lipopolysaccharide-induced activation of a microglial cell line, BV-2, by blocking NF-kappaB and AP-1. Phytother. Res., 24Suppl 1, S29–S34 (2010).
Perez, R. L., Ritzenthaler, J. D., and Roman, J., Transcriptional regulation of the interleukin-1beta promoter via fibrinogen engagement of the CD18 integrin receptor. Am. J. Respir. Cell Mol. Biol., 20, 1059–1066 (1999).
Rauwald, H. W., Brehm, O., and Odenthal, K. P., The involvement of a Ca2+ channel blocking mode of action in the pharmacology of Ammi visnaga fruits. Planta Med., 60, 101–105 (1994).
Ray, B. and Lahiri, D. K., Neuroinflammation in Alzheimer’s disease: different molecular targets and potential therapeutic agents including curcumin. Curr. Opin. Pharmacol., 9, 434–444 (2009).
Saraiva, M. and O’garra, A., The regulation of IL-10 production by immune cells. Nat. Rev. Immunol., 10, 170–181 (2010).
Saud, K., Herrera-Molina, R., and Von Bernhardi, R., Proand anti-inflammatory cytokines regulate the ERK pathway: implication of the timing for the activation of microglial cells. Neurotox. Res., 8, 277–287 (2005).
Strle, K., Zhou, J. H., Shen, W. H., Broussard, S. R., Johnson, R. W., Freund, G. G., Dantzer, R., and Kelley, K. W., Interleukin-10 in the brain. Crit. Rev. Immunol., 21, 427–449 (2001).
Thompson, W. L., Karpus, W. J., and Van Eldik, L. J., MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult. J. Neuroinflammation, 5, 35 (2008).
Tuttolomondo, A., Di Raimondo, D., Di Sciacca, R., Pinto, A., and Licata, G., Inflammatory cytokines in acute ischemic stroke. Curr. Pharm. Des., 14, 3574–3589 (2008).
Tzeng, S. F., Hsiao, H. Y., and Mak, O. T., Prostaglandins and cyclooxygenases in glial cells during brain inflammation. Curr. Drug Targets Inflamm. Allergy, 4, 335–340 (2005).
Ubeda, A., Tejerina, T., Tamargo, J., and Villar, A., Effects of khellin on contractile responses and 45Ca2+ movements in rat isolated aorta. J. Pharm. Pharmacol., 43, 46–48 (1991).
Udalova, I. A. and Kwiatkowski, D., Interaction of AP-1 with a cluster of NF-kappa B binding elements in the human TNF promoter region. Biochem. Biophys. Res. Commun., 289, 25–33 (2001).
Vanachayangkul, P., Byer, K., Khan, S., and Butterweck, V., An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells. Phytomedicine, 17, 653–658 (2010).
Wang, J., Barke, R. A., Charboneau, R., Loh, H. H., and Roy, S., Morphine negatively regulates interferon-gamma promoter activity in activated murine T cells through two distinct cyclic AMP-dependent pathways. J. Biol. Chem., 278, 37622–37631 (2003).
Yang, X., Du, L., Tang, X., Jung, S. Y., Zheng, B., Soh, B. Y., Kim, S. Y., Gu, Q., and Park, H., Brevicompanine E reduces lipopolysaccharide-induced production of proinflammatory cytokines and enzymes in microglia by inhibiting activation of activator protein-1 and nuclear factorkappaB. J. Neuroimmunol., 216, 32–38 (2009).
Zhang, F., Liu, J., and Shi, J. S., Anti-inflammatory activities of resveratrol in the brain: role of resveratrol in microglial activation. Eur. J. Pharmacol., 636, 1–7 (2010).
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Lee, JK., Jung, JS., Park, SH. et al. Anti-inflammatory effect of visnagin in lipopolysaccharide-stimulated BV-2 microglial cells. Arch. Pharm. Res. 33, 1843–1850 (2010). https://doi.org/10.1007/s12272-010-1117-1
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DOI: https://doi.org/10.1007/s12272-010-1117-1