Inhibitory effect of a 2,4-bis(4-hydroxyphenyl)-2-butenal diacetate on neuro-inflammatory reactions via inhibition of STAT1 and STAT3 activation in cultured astrocytes and microglial BV-2 cells
- Authors
- Kim, Jin A.; Yun, Hyung-Mun; Jin, Peng; Lee, Hee Pom; Han, Jin Yi; Udumula, Venkatareddy; Moon, Dong Cheul; Han, Sang Bae; Oh, Ki Wan; Ham, Young Wan; Jung, Heon-Sang; Song, Ho Sueb; Hong, Jin Tae
- Issue Date
- Apr-2014
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Anti-amyloidogenesis; Anti-neuroinflammation; NF-kappa B; STAT1; STAT3; 2,4-Bis(4-hydroxyphenyl)but-2-enal diacetate
- Citation
- NEUROPHARMACOLOGY, v.79, pp.476 - 487
- Journal Title
- NEUROPHARMACOLOGY
- Volume
- 79
- Start Page
- 476
- End Page
- 487
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12737
- DOI
- 10.1016/j.neuropharm.2013.06.032
- ISSN
- 0028-3908
- Abstract
- 2,4-Bis(p-hydroxyphenyl)-2-butenal (Butenal), a tyrosine-fructose Maillard reaction product has been demonstrated as an effective compound for prevention of neuroinflammatory diseases. However, this compound was vulnerable to environmental factors. Our research has been continuously made to improve druggability of Butenal and identified 2,4-bis(4-hydroxyphenyl)but-2-enal diacetate (HPBD) as an alternative. Herein, to investigate potential anti-neuroinflammatory and anti-amyloidogenic effects of HPBD, we treated HPBD (0.5, 1, and 2 mu g/ml) on the lipopolysaccharides (LPS) (1 mu g/ml) stimulated astrocytes and microglial BV-2 cell. HPBD inhibited LPS-induced NO and ROS production, and LPS-elevated expression of iNOS, COX2, beta-site APP-cleaving enzyme 1 (BACE1), C99, and A beta(1-42) levels as well as attenuation of beta-secretase activities. The activation of nuclear factor-kappaB (NF-kappa B), signal transducer and activator of transcription1 (STAT1), and STAT3 was concomitantly inhibited by HPBD. Moreover, siRNA targeting STAT3 abolished HPBD-induced inhibitory effects on neuro-inflammation and amyloidogenesis. In addition, pull down assay and docking model showed interaction of HPBD with STAT3. These findings suggest that HPBD may be useful and potentially therapeutic choices for the treatment of neuroinflammatory diseases. (C) 2013 Elsevier Ltd. All rights reserved.
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