Inflammation plays a central role in the pathogenesis of several brain disorders and neuronal injury, and it develops as a consequence of glial cell activation. Activated microglial cells generate potentially damaging nitric oxide, oxygen free radicals, prostanoids, and pro-inflammatory cytokines. Naturally occurring polyphenols have recently received attention for their potential protective effect on neurodegenerative disorders characterized by microglial activation, due to their anti-inflammatory and antioxidant properties. In the present study, we investigated, using an in vitro model of primary microglia, the ability of 1-phenyl-6,7-dihydroxy-isochroman (encoded L 137), a natural polyphenolic compound, to inhibit microglia activation induced by an inflammatory insult. So, L137 effects (1-100 mu M) on production of pro-inflammatory mediators in lipopolysaccharide (LPS)-activated microglial cells were evaluated. The expression of inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) as well as of the nuclear transcription Factor-kappa B (NF-kappa B) was also performed in cellular lysates by Immunoblot. L137 significantly reduced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 secretion, as well as nitric oxide (NO) and prostanoids [Thromboxane (TX)B-2, prostaglandin (PG)E-2] production in activated microglial cells. Western blot analyses showed an inhibitory effect of L137 on the iNOS and COX-2 expression, mediated by a modulation of redox-sensitive nuclear transcriptional factor (NF)-kappa B, known to control a wide array of genes involved in inflammation. In conclusion, this study demonstrate that L137 is able to inhibit the production of pro-inflammatory and neurotoxic mediators by LPS-activated microglial cells thus suggesting L137 as a potential lead compound for drug development for neurodegenerative disorders where microglia-mediated inflammatory responses play an important pathogenic role. (C) 2013 Elsevier Inc. All rights reserved.

1-Phenyl-6,7-dihydroxy-isochroman inhibits inflammatory activation of microglia / Togna, Anna Rita; Latina, Valentina; Trefiletti, Giuliana; Guiso, Marcella; Sabina, Moschini; Togna, Giuseppina Ines. - In: BRAIN RESEARCH BULLETIN. - ISSN 0361-9230. - STAMPA. - 95:(2013), pp. 33-39. [10.1016/j.brainresbull.2013.03.001]

1-Phenyl-6,7-dihydroxy-isochroman inhibits inflammatory activation of microglia

TOGNA, Anna Rita;LATINA, VALENTINA;TREFILETTI, GIULIANA;GUISO, Marcella;TOGNA, Giuseppina Ines
2013

Abstract

Inflammation plays a central role in the pathogenesis of several brain disorders and neuronal injury, and it develops as a consequence of glial cell activation. Activated microglial cells generate potentially damaging nitric oxide, oxygen free radicals, prostanoids, and pro-inflammatory cytokines. Naturally occurring polyphenols have recently received attention for their potential protective effect on neurodegenerative disorders characterized by microglial activation, due to their anti-inflammatory and antioxidant properties. In the present study, we investigated, using an in vitro model of primary microglia, the ability of 1-phenyl-6,7-dihydroxy-isochroman (encoded L 137), a natural polyphenolic compound, to inhibit microglia activation induced by an inflammatory insult. So, L137 effects (1-100 mu M) on production of pro-inflammatory mediators in lipopolysaccharide (LPS)-activated microglial cells were evaluated. The expression of inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) as well as of the nuclear transcription Factor-kappa B (NF-kappa B) was also performed in cellular lysates by Immunoblot. L137 significantly reduced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 secretion, as well as nitric oxide (NO) and prostanoids [Thromboxane (TX)B-2, prostaglandin (PG)E-2] production in activated microglial cells. Western blot analyses showed an inhibitory effect of L137 on the iNOS and COX-2 expression, mediated by a modulation of redox-sensitive nuclear transcriptional factor (NF)-kappa B, known to control a wide array of genes involved in inflammation. In conclusion, this study demonstrate that L137 is able to inhibit the production of pro-inflammatory and neurotoxic mediators by LPS-activated microglial cells thus suggesting L137 as a potential lead compound for drug development for neurodegenerative disorders where microglia-mediated inflammatory responses play an important pathogenic role. (C) 2013 Elsevier Inc. All rights reserved.
2013
anti-inflammatory activity; pro-inflammatory mediators; cyclooxygenase; microglia activation; isochromans
01 Pubblicazione su rivista::01a Articolo in rivista
1-Phenyl-6,7-dihydroxy-isochroman inhibits inflammatory activation of microglia / Togna, Anna Rita; Latina, Valentina; Trefiletti, Giuliana; Guiso, Marcella; Sabina, Moschini; Togna, Giuseppina Ines. - In: BRAIN RESEARCH BULLETIN. - ISSN 0361-9230. - STAMPA. - 95:(2013), pp. 33-39. [10.1016/j.brainresbull.2013.03.001]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/514839
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