Anti-Inflammatory Effect of Methylpenicinoline from a Marine Isolate of Penicillium sp. (SF-5995): Inhibition of NF-κB and MAPK Pathways in Lipopolysaccharide-Induced RAW264.7 Macrophages and BV2 Microglia

Abstract

Abstract:In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1) was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production by suppressing the expression of inducible NO synthase (iNOS) in RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E2 (PGE2) production by suppressing cyclooxygenase-2 (COX-2) expression in a concentration-dependent manner (from 10 μM to 80 μM) without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1β (IL-1β). In a further study designed to elucidate the mechanism of its anti-inflammatory effects, compound 1 was shown to block OPEN ACCESSMolecules 2014, 19 18074 nuclear factor-kappa B (NF-κB) activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-α (IκB-α), thereby suppressing the nuclear translocation of NF-κB dimers, namely p50 and p65, that are known to be crucial molecules associated with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation of mitogen-activated protein kinase (MAPK) pathways. Taken together, the results suggest that compound 1 might be a valuable therapeutic agent for the treatment of anti-inflammatory and anti-neuroinflammatory diseases.

Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via Inhibition of STAT3

“…RAW 264.7 cells were plated in 12-well plates (1×10 5 cells/well) and transiently transfected with STAT3-Luc plasmid using a mixture of plasmid and Lipofectamine 3000 in OPTIMEM according to manufacturer’s specification (Invitrogen, Carlsbad, CA, USA) for 24 h ( Kim et al ., 2012 ; Kim et al ., 2014 ). The transfected cells were treated with 1, 2 and 5 μM carnosol for another 24 h. Luciferase activity was measured by using a luciferase assay kit (Promega, Madison, WI, USA), and the results were read on a luminometer as described by the manufacturer’s specifications (WinGlow, Bad Wildbad, Germany).…”

Evaluation of anti-inflammatory activity of compounds isolated from the rhizome of Ophiopogon japonicas

“…The cytotoxicity of the isolated compounds toward RAW264.7 macrophage cells were evaluated by a conventional MTT assay as reported previously [15]. RAW 264.7 cells (1.0 × 10 5 cells/well) were given a volume of 100 μl to 96-well plates and incubated for 24 h and then treated with or without different concentrations of compounds (1, 5, 25, 50 and 100 μg/mL).…”

Prenylated Flavonoids from Cudrania tricuspidata Suppress Lipopolysaccharide-Induced Neuroinflammatory Activities in BV2 Microglial Cells

“…WP-2014-12) was deposited at the Herbarium of the College of Pharmacy, Wonkwang University (Iksan, Korea). Prenylated flavonoids ( Figure 1 ) were isolated from the methanol extract of C. tricuspidata (Moraceae) by various chromatographic methods, and the structures were determined mainly by analysis of MS and NMR data [ 24 , 43 ].…”

“…Optical density was measured at 590 nm using a microplate reader (Bio-Rad, Hercules, CA, USA). The optical density of the formazan formed in control (untreated) cells was considered to represent 100% cell viability [ 43 , 44 ].…”

“…The qPCR conditions were established by following the manufacturer’s instructions. The data were analyzed using StepOne software (Applied Biosystems) and the cycle numbers at the linear amplification threshold ( C t ) values for the endogenous control gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the target gene were recorded [ 43 ].…”