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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
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  • huijie Guo,
  • xingyan Luo,
  • shuxia Yang,
  • yang Liu,
  • chunfen Mo
huijie Guo
Chengdu Medical College
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xingyan Luo
Chengdu Medical College
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shuxia Yang
Chengdu Medical College
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yang Liu
Chengdu Medical College
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chunfen Mo
Chengdu Medical College

Corresponding Author:mochunfen@cmc.edu.cn

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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.
20 Sep 2023Submitted to Immunity, Inflammation and Disease
26 Sep 2023Submission Checks Completed
26 Sep 2023Assigned to Editor
26 Sep 2023Review(s) Completed, Editorial Evaluation Pending
03 Oct 2023Reviewer(s) Assigned