Vermelhotin, an Anti-inflammatory Agent, Suppresses Nitric Oxide Production in RAW 264.7 Cells via p38 Inhibition

Abstract

Vermelhotin exhibited potential anti-inflammatory activity through inhibition of nitric oxide production (IC₅₀ = 5.35 ± 0.59 μM) in LPS-stimulated RAW 264.7 macrophage cells. Vermelhotin suppressed expression of inducible nitric oxide synthase (iNOS) at mRNA and protein levels, in a dose-dependent manner. Mechanistic studies revealed that vermelhotin abrogated upstream signaling of iNOS expression by selectively inhibiting p38 phosphorylation, while ERK and JNK activations were not affected.

Dysifragilones A–C, Unusual Sesquiterpene Aminoquinones and Inhibitors of NO Production from the South China Sea Sponge Dysidea fragilis

“…Of the three compounds, 1 exhibited the most potent inhibitory activity, with an IC 50 value of 6.61 μm. Considering that a number of reported natural products and synthetic compounds bearing α,β-unsaturated carbonyl functional groups have been found to show potent inhibitory activity on NO production, [3,4,[23][24][25][26] the inhibitory activity might be the result of Michael-type additions of biosynthetic thiol and/or related groups to the α,β-unsaturated carbonyl system. [27,28] [a] Hydrocortisone was used as a positive control.…”

“…[1] Macrophages, as key players in inflammation, are the main NO producers when activated by inflammatory mediators. [3,4] Marine sponges harbor compounds with a diverse range of chemical structures to defend against environmental stress factors such as predation, overgrowth by fouling organisms, or competition for space, [5] and this makes them rich sources of new natural products based on unique chemical scaffolds and displaying a spectrum of potent bio-960 chroism (ECD) spectra. [3,4] Marine sponges harbor compounds with a diverse range of chemical structures to defend against environmental stress factors such as predation, overgrowth by fouling organisms, or competition for space, [5] and this makes them rich sources of new natural products based on unique chemical scaffolds and displaying a spectrum of potent bio-960 chroism (ECD) spectra.…”

“…[2] Inhibition of NO production is a key anti-inflammatory approach and provides a strategy for drug development. [3,4] Marine sponges harbor compounds with a diverse range of chemical structures to defend against environmental stress factors such as predation, overgrowth by fouling organisms, or competition for space, [5] and this makes them rich sources of new natural products based on unique chemical scaffolds and displaying a spectrum of potent bio-chroism (ECD) spectra. The inhibitory activity of each compound on the production of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages was evaluated.…”

Anti-Inflammatory Effect of Mangostenone F in Lipopolysaccharide-Stimulated RAW264.7 Macrophages by Suppressing NF-κB and MAPK Activation

“…NO is a free radical produced by nitric oxide synthase (NOS), which exists as three NOS isoforms: endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). Macrophages after LPS stimulation produce NO by up-regulating iNOS expression through mitogen-activated protein kinases (MAPK) and NF-κB signaling pathways (Pansanit et al ., 2013). In response to macrophage activation, LPS stimulates a Toll-like receptor 4 (TLR4)-mediated myeloid differentiation factor (MyD88)-dependent pathway, which in turn activates the transforming growth factor-β-activated protein kinase 1 (TAK1), which subsequently results in activation of nuclear factor-κB (NF-κB) and activating protein-1 (AP-1), and produces inflammatory cytokines including TNF-α, IL-6, and IL-1β (Kawai and Akira, 2006).…”

“…In response to macrophage activation, LPS stimulates a Toll-like receptor 4 (TLR4)-mediated myeloid differentiation factor (MyD88)-dependent pathway, which in turn activates the transforming growth factor-β-activated protein kinase 1 (TAK1), which subsequently results in activation of nuclear factor-κB (NF-κB) and activating protein-1 (AP-1), and produces inflammatory cytokines including TNF-α, IL-6, and IL-1β (Kawai and Akira, 2006). Therefore, inhibition of these inflammatory mediators has been considered as an effective strategy for the development of anti-inflammatory drugs (Shin et al ., 2010; Pansanit et al ., 2013). …”