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001-es BibID:	BIBFORM121125
035-os BibID:	(WOS)001144603900001
Első szerző:	Tao, Lingxue
Cím:	JE-133 suppresses LPS-induced neuroinflammation associated with the regulation of JAK/STAT and Nrf2 signaling pathways / Lingxue Tao, Weichen Yu, Ziyi Liu, Danfeng Zhao, Sijin Lin, Dóra Szalóki, Máté Kicsák, Tibor Kurtán, Haiyan Zhang
Dátum:	2024
ISSN:	1948-7193
Megjegyzések:	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-1[beta]), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), 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-? 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.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk JAK/STAT LPS Nrf2 microglia neuroinflammation
Megjelenés:	ACS Chemical Neuroscience. - 15 : 2 (2024), p. 258-267. -
További szerzők:	Yu, Weichen Liu, Ziyi Zhao, Danfeng Lin, Sijin Vargáné Szalóki Dóra (1989-) (vegyész) Kicsák Máté (1990-) (gyógyszerész) Kurtán Tibor (1973-) (vegyész, angol szakfordító) Zhang, Hai-Yan
Pályázati támogatás:	K138672 OTKA
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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