Anti-inflammatory effect of BMP326, a novel benzothiazole derivative:
Possible involvement of the NF-κB and MAPKs Signaling Pathways in
LPS-induced RAW264.7 macrophages
Abstract
Background: Benzothiazole and its derivatives have been extensive
studied due to their versatile biological properties and pharmaceutical
applications. We recently found that the BMP326
(1-(1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)-1H-pyrazol-5-ol), a novel
benzothiazole derivative, have anti-inflammatory properties in
lipopolysaccharide(LPS)-induced RAW264.7 macrophages and there were no
relevant reports previously. Methods and Results: Treatment with
BMP326(5, 10 and 20 μM) can significantly inhibit nitric oxide
production and down-regulate mRNA expression of nitric oxide synthase
(iNOS) and cyclooxygenase-2 (COX-2) but did not cause significant
cytotoxicity on RAW264.7 macrophages. It is also observed BMP326 can
inhibit LPS-stimulated interleukin (IL)-6, interleukin(IL)-1β, tumor
necrosis factor (TNF)-α production depending on its dosage. The gene
transcription levels of IL-6, IL-1β and TNF-α were reduced under BMP326
exposure in LPS-treated RAW264.7 cells. In addition, we explored the
inhibitory mechanisms of BMP326 on the production of pro-inflammatory
mediators. The results showed that BMP326 inhibited nuclear factor kappa
B (NF-κB) activation by reducing the phosphorylation of p65 and IκBα.
Moreover, the phosphorylation of p38 MAPK (p38), extracellular
signal-regulated kinases 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK)
in RAW264.7 cells which are stimulated with LPS were suppressed in a
dose-dependent manner. Conclusions: In summary, these results suggest
that BMP326 exerts anti-inflammatory properties via suppression of the
NF-κB and MAPKs signaling pathways.