BDMC33, A Curcumin Derivative Suppresses Inflammatory Responses in Macrophage-Like Cellular System: Role of Inhibition in NF-κB and MAPK Signaling Pathways

Abstract

Our preliminary screening has shown that curcumin derivative BDMC33 [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] exerted promising nitric oxide inhibitory activity in activated macrophages. However, the molecular basis and mechanism for its pharmacological action is yet to be elucidated. The aim of this study was to investigate the anti-inflammatory properties of BDMC33 and elucidate its underlying mechanism action in macrophage cells. Our current study demonstrated that BDMC33 inhibits the secretion of major pro-inflammatory mediators in stimulated macrophages, and includes NO, TNF-α and IL-1β through interference in both nuclear factor kappaB (NF-κB) and mitogen activator protein kinase (MAPK) signaling cascade in IFN-γ/LPS-stimulated macrophages. Moreover, BDMC33 also interrupted LPS signaling through inhibiting the surface expression of CD-14 accessory molecules. In addition, the inhibitory action of BDMC33 not only restricted the macrophages cell (RAW264.7), but also inhibited the secretion of NO and TNF-α in IFN-γ/LPS-challenged microglial cells (BV-2). The experimental data suggests the inflammatory action of BDMC33 on activated macrophage-like cellular systems, which could be used as a future therapeutic agent in the management of chronic inflammatory diseases.

Amauroderma rugosum(Blume & T. Nees) Torrend: Nutritional Composition and Antioxidant and Potential Anti-Inflammatory Properties

“…Moreover, the EE and HF significantly ( P < 0.05) promoted proliferation of RAW264.7 cells at a higher concentration. During inflammation, numerous inflammatory mediators such as NO, cytokines, and prostaglandin E 2 are produced [20]. However, excessive production of NO is harmful to living organisms.…”

“…The nitric oxide (NO) was determined according to the method reported by Lee et al [20]. RAW264.7 cells (4 × 10 5 cells/well) were seeded into 96-well plates and incubated at 37°C in a humidified atmosphere containing 5% CO 2 for 24 hrs.…”

“…The nitric oxide radical scavenging assay was performed according to the method described by Lee et al [20] with slight modifications. Briefly, 10  μ L of A. rugosum extracts (0.05, 0.5, 5, 50, or 500  μ g/mL) was added into 96-well plates.…”

Attenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-&kappa;B pathways

“…19,20 The exposure of macrophages to pro-inflammatory stimuli causes a rapid phosphorylation of the IkB protein at two critical serine residues (Ser 32 and Ser 36) by IkB kinase (IKK). 21,22 This results in IkB protein ubiquitination followed by proteasome-mediated degradation, and then NF-κB translocates to the nucleus to promote the transcription of inflammation-associated target genes. [23][24][25] Furthermore, NF-κB is important for LPS-induced inflammation as it regulates a plethora of inflammatory genes (including TNF-α, IL-1, and iNOS) by binding to transcription-regulatory elements in a nucleotide sequence-specific manner.…”

Curcumin and its allied analogues: epigenetic and health perspectives - a review

“…It downregulates the production of tumour necrosis factors including IL-1β and TNF-α, as well as it also suppresses the activation of AP-1 and nuclear factor-κB (NF-κB) through hindering phosphorylation of I-κB by inactivation of I-κB kinase complex (Lee et al 2012). It inhibits c-fos, c-jun, and activator protein-1 owing to its DNA binding activity.…”