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1-Phenil-6,7-dihydroxy-isochroman inhibits inflammatory activation of microglia.
Brain Res Bull 2013; 95:33-9BR

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 μM) 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-κB) was also performed in cellular lysates by Immunoblot. L137 significantly reduced tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 secretion, as well as nitric oxide (NO) and prostanoids [Thromboxane (TX)B2, prostaglandin (PG)E2] 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)-κB, 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.

Authors+Show Affiliations

Department of Physiology and Pharmacology Vittorio Erspamer, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23558156

Citation

Togna, Anna Rita, et al. "1-Phenil-6,7-dihydroxy-isochroman Inhibits Inflammatory Activation of Microglia." Brain Research Bulletin, vol. 95, 2013, pp. 33-9.
Togna AR, Latina V, Trefiletti G, et al. 1-Phenil-6,7-dihydroxy-isochroman inhibits inflammatory activation of microglia. Brain Res Bull. 2013;95:33-9.
Togna, A. R., Latina, V., Trefiletti, G., Guiso, M., Moschini, S., & Togna, G. I. (2013). 1-Phenil-6,7-dihydroxy-isochroman inhibits inflammatory activation of microglia. Brain Research Bulletin, 95, pp. 33-9. doi:10.1016/j.brainresbull.2013.03.001.
Togna AR, et al. 1-Phenil-6,7-dihydroxy-isochroman Inhibits Inflammatory Activation of Microglia. Brain Res Bull. 2013;95:33-9. PubMed PMID: 23558156.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 1-Phenil-6,7-dihydroxy-isochroman inhibits inflammatory activation of microglia. AU - Togna,Anna Rita, AU - Latina,Valentina, AU - Trefiletti,Giuliana, AU - Guiso,Marcella, AU - Moschini,Sabina, AU - Togna,Giuseppina I, Y1 - 2013/04/01/ PY - 2012/11/07/received PY - 2013/03/04/revised PY - 2013/03/05/accepted PY - 2013/4/6/entrez PY - 2013/4/6/pubmed PY - 2014/2/11/medline SP - 33 EP - 9 JF - Brain research bulletin JO - Brain Res. Bull. VL - 95 N2 - 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 μM) 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-κB) was also performed in cellular lysates by Immunoblot. L137 significantly reduced tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 secretion, as well as nitric oxide (NO) and prostanoids [Thromboxane (TX)B2, prostaglandin (PG)E2] 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)-κB, 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. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/23558156/1_Phenil_67_dihydroxy_isochroman_inhibits_inflammatory_activation_of_microglia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(13)00044-0 DB - PRIME DP - Unbound Medicine ER -