Effect of Benzoylsalicylic Acid on IKK-Beta Kinase and NF-κB Pathway in Murine Macrophage raw 264.7 Cells

Abstract The transcription factor NF-κB regulates a large array of genes of immune and inflammatory responses. Deregulated NF-κB signalling is implicated in the pathogenesis and broad spectrum of human inflammatory disorders and malignancies. The mechanism for NF-κB activation is the inducible degradation of IκB, triggered through its site-specific phosphorylation by a multi-subunit IκB kinase (IKK) complex. Aspirin (acetylsalicylic acid) a well-known anti-inflammatory agent that binds to ATP binding pocket of IKKβ and inhibits its kinase activity. However, several side effects of aspirin due to the inactivation of COX-1 limits the therapeutic usage of ASA. Here we have demonstrate the effect of a plant phenolic compound benzoylsalicylic acid (BzSA) isolated first time in plants a potent anti-viral compound inhibits Tobacco mosaic virus (TMV) and enhance the plant defense response (Samuel et all 2016&2017) inhibit the IKKβ mediated NF-κB pathway higher than aspirin. Our In-vitro COX enzymatic assays with BzSA have shown less COX-1 and high COX-2 inhibition as compared to ASA. Western blotting analysis of Raw 264.7 cells that were pre-treated with BzSA down-regulated LPS stimulated pIKK-β, pIκB, NF-κBp65, TNF-α, COX-1, COX-2, 5-LOX, IL-1β, and IL-6 higher than ASA. Therefore, our observations suggested that the potencial therapeutic value of BzSA an upcoming new inhibitor of NF-KB pathway and the dual inhibitor of COX2/5-LOX without effecting the usefull COX-1. Hence useful as an anti-inflammatory agent like ASA.