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KMID : 0624620190520080508
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BMB Reports
2019 Volume.52 No. 8 p.508 ~ p.513
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An alpha-lipoic acid-decursinol hybrid compound attenuates lipopolysaccharide-mediated inflammation in BV2 and RAW264.7 cells
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Kwon Mi-Youn
Park Ji-Won
Kim Sang-Min
Lee Joo-Weon
Cho Hyeong-Jin
Park Jeong-Ho
Han Inn-Oc
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Abstract
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In this study, the anti-inflammatory effects of α-lipoic acid (LA) and decursinol (Dec) hybrid compound LA-Dec were evaluated and compared with its prodrugs, LA and Dec. LA-Dec dose-dependently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) generation in BV2 mouse microglial cells. On the other hand, no or mild inhibitory effect was shown by the 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 dosedependent manner in both BV2 and mouse macrophage, RAW264.7 cells. Furthermore, LA-Dec inhibited LPS-induced expressions of iNOS, COX-2, interleukin-6, tumor necrosis factor-α, and interleukin-1β 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 LA-Dec hybrid compound as a potential therapeutic agent for inflammatory diseases of the peripheral and central nervous systems.
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KEYWORD
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Decursinol, Hybrid molecule, iNOS, Lipoic acid, Lipopolysaccharide
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