Your browser doesn't support javascript.
loading
JE-133 Suppresses LPS-Induced Neuroinflammation Associated with the Regulation of JAK/STAT and Nrf2 Signaling Pathways.
Tao, Lingxue; Yu, Weichen; Liu, Ziyi; Zhao, Danfeng; Lin, Sijin; Szalóki, Dóra; Kicsák, Máté; Kurtán, Tibor; Zhang, Haiyan.
Afiliación
  • Tao L; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Yu W; Lingang Laboratory, Shanghai 200031, China.
  • Liu Z; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Zhao D; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Lin S; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Szalóki D; Nanchang University, Jiangxi 330031, China.
  • Kicsák M; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Kurtán T; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Zhang H; University of Chinese Academy of Sciences, Beijing 100049, China.
ACS Chem Neurosci ; 15(2): 258-267, 2024 01 17.
Article en En | MEDLINE | ID: mdl-38181172
ABSTRACT
Neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, and interrupting the microglial-mediated neuroinflammation has been suggested as a promising strategy to delay or prevent the progression of neurodegeneration. In this study, we investigated the effects of JE-133, an optically active isochroman-2H-chromene conjugate containing a 1,3-disubstituted isochroman unit, on lipopolysaccharide (LPS)-induced microglial neuroinflammation and underlying mechanisms both in vitro and in vivo. First, JE-133 treatment decreased LPS-induced overproduction of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nitrite, and nitric oxide synthase (iNOS) in BV2 microglial cells. Further study revealed that JE-133 downregulated the phosphorylation level of JAK/STAT and upregulated the protein level of Nrf2/HO-1 in LPS-stimulated BV2 microglial cells and verified that JE-133 directly bound to Keap1 by a pull-down assay. Next, JE-133 administration also inhibited neuroinflammation in vivo, as indicated by a reduced CD11b protein level and an overexpressed mRNA level of the pro-inflammatory cytokine TNF-α in the hippocampus of LPS-injected mice. Moreover, the regulative effects of JE-133 on the JAK/STAT and Nrf2/HO-1 pathways were also verified in the hippocampus of LPS-injected mice. Taken together, our study for the first time reports that JE-133 exhibits inhibitory effects against LPS-stimulated neuroinflammation both in vitro and in vivo, which might be associated with the simultaneous regulation of the JAK/STAT and Nrf2 pathways. Our findings may provide important clues for the discovery of effective drug leads/candidates against neuroinflammation-associated neurodegeneration.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lipopolisacáridos / Factor 2 Relacionado con NF-E2 Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: ACS Chem Neurosci Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lipopolisacáridos / Factor 2 Relacionado con NF-E2 Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: ACS Chem Neurosci Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos