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Comparative study of β-boswellic acid and its analogue, BA-25 for anti-inflammatory potential.BA-25 strongly inhibits the expression iNOS, COX-2 in LPS-evoked RAW 264.7 cells.Also suppresses the expression of TNFα, IL-1β, IL-6, PGE2 & LTB4 efficiently.Checks inflammatory mediators via ROS-dependent activation of NF-κB/IκBα axis.BA-25 also shows modulatory potential in paw oedema modelled BALB/c mice.Natural product derivatives have proven to be cutting edge window for drug discovery and development. BA-25 (3-α-o-acetoxy-4β-amino-11-oxo-24-norurs-12-ene) an amino analogue of β-boswellic acid exhibited inhibition of TNF-α and IL-6 in THP-1 cells as demonstrated previously, however, the effect on principal inflammatory mediators such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and the pathways that mediate this function remains unknown. This study was designed to examine the comparative anti-inflammatory activity of BA-25 with its parent compound, β boswellic acid both in vitro and in vivo. The effect of BA and BA-25 on suppression of NO, PGE2, LTB4, COX-2 in LPS-stimulated RAW 264.7 cells was determined by ELISA, RT-PCR and ROS by flow cytometry. Phosphorylation of NF-kBp65, IKB degradation was determined by western blotting and also the nuclear localization of NF-kBp65 was assessed by immunofluorescence. Furthermore, this study was extended on Carrageenan induced paw oedema modelled BALB/c mice. A novel derivative BA-25, reported first time notably decreased the LPS (1 μg/mL) induced upregulation in the transcription of TNF-α, IL-6, iNOS and COX-2. Also the protein expression of iNOS and COX-2 as well as their downstream products NO and PGE2 respectively, were also decreased efficiently at a concentration of 10 μM than BA. Moreover, LPS upregulated NF-kB p65 expression and IκB degradation was significantly decreased after BA-25 treatment. In addition, the treatment of BA-25 also restored the paw oedema and decreased the magnitude of histopathological alterations. Our data together suggested that BA-25 might be regarded as prospective therapeutic anti-inflammatory alternative and demands further investigation in pharmacological studies.