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Nordalbergin Exerts Anti-Neuroinflammatory Effects by Attenuating MAPK Signaling Pathway, NLRP3 Inflammasome Activation and ROS Production in LPS-Stimulated BV2 Microglia

Authors :
Jung Lo
Hsin-En Wu
Ching-Chih Liu
Kun-Che Chang
Po-Yen Lee
Po-Len Liu
Shu-Pin Huang
Pei-Chang Wu
Tzu-Chieh Lin
Yu-Hung Lai
Yo-Chen Chang
Yuan-Ru Chen
Sheng-I Lee
Yu-Kai Huang
Shu-Chi Wang
Chia-Yang Li
Source :
International Journal of Molecular Sciences, Vol 24, Iss 8, p 7300 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1β production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression.

Details

Language :
English
ISSN :
24087300, 14220067, and 16616596
Volume :
24
Issue :
8
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.1399ac2f79764234bc1f06d12478eb00
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms24087300