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An alpha-lipoic acid-decursinol hybrid compound attenuates lipopolysaccharide-mediated inflammation in BV2 and RAW264.7 cells
Mi-Youn Kwon1, Jiwon Park1, Sang-Min Kim1, Jooweon Lee1, Hyeongjin Cho2, Jeong-Ho Park3, Inn-Oc Han1,*,#
1Department of Physiology and Biophysics, College of Medicine and 2Department of Chemistry, Inha University,
3Department of Chemical & Biological Engineering, Hanbat National University
Abstract
The anti-inflammatory effects of メ-lipoic acid (LA) and the decursinol (Dec) hybrid compound LA-Dec were evaluated and compared with its prodrugs, LA and Dec. LA-Dec dose-dependently inhibited lipopolysaccharide (LPS) and generated nitric oxide (NO) in BV2 cells, whereas no or mild inhibitory effect was shown by Dec and LA, respectively. LA-Dec demonstrated dose-dependent protection from activation-induced cell death in BV2 cells. LA-Dec, but not LA or Dec individually, inhibited LPS-induced increased expressions of induced NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in a dose-dependent manner in both BV2 and RAW264.7 cells. Furthermore, LA-Dec inhibited LPS-induced expressions of iNOS, COX-2, interleukin-6, tumor necrosis factor-メ, and interleukin-1モ mRNA in BV2 cells, whereas the same concentration of LA or Dec was ineffective. Signaling studies demonstrated that LA-Dec inhibited LPS-activated signal transducer and activator of transcription 3 and protein kinase B activation, but not nuclear factor-kappa B or mitogen-activated protein kinase signaling. The data implicate the LA-Dec hybrid compound as a potential therapeutic agent for inflammatory diseases of the peripheral and central nervous systems.
Abstract, Accepted Manuscript(in press) [Submitted on May 20, 2019, Accepted on June 13, 2019]
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