The amino analogue of β-boswellic acid efficiently attenuates the release of pro-inflammatory mediators than its parent compound through the suppression of NF-κB/IκBα signalling axis

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2018-07, Vol.107, p.93-104
• Main Authors: Gupta, Shilpa, Ahsan, Aitizaz Ul, Wani, Abubakar, Khajuria, Vidushi, Nazir, Lone A., Sharma, Simmi, Bhagat, Asha, Raj Sharma, Parduman, Bhardwaj, Subhash, Peerzada, Kaiser J., Ali Shah, Bhahwal, Ahmed, Zabeer
• Format: Article
• Language: English
• Subjects: 3-α-o-acetoxy-4β-amino-11-oxo-24-norurs-12-ene (BA-25); Animals; Anti-Inflammatory Agents - pharmacology; Cell Line; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytokines - metabolism; Edema - drug therapy; Edema - metabolism; Inflammation - drug therapy; Inflammation - metabolism; Inflammation Mediators - metabolism; Lipopolysaccharide; Mice; Mice, Inbred BALB C; Mouse paw oedema; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha - metabolism; Nitric oxide; Nitric Oxide Synthase Type II - metabolism; RAW 264.7 Cells; Signal Transduction - drug effects; Triterpenes - pharmacology; Up-Regulation - drug effects; β-Boswellic acid (BA)
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2017.12.004

[Display omitted] •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.