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
| Autor: | Simmi Sharma, Shilpa Gupta, Bhahwal Ali Shah, Abubakar Wani, Vidushi Khajuria, Zabeer Ahmed, Kaiser J. Peerzada, Aitizaz Ul Ahsan, Subhash Bhardwaj, Lone A. Nazir, Asha Bhagat, Parduman R. Sharma |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharide Immunology Anti-Inflammatory Agents Nitric Oxide Synthase Type II Biochemistry Nitric oxide Cell Line 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Downregulation and upregulation NF-KappaB Inhibitor alpha In vivo Immunology and Allergy Animals Edema Molecular Biology Inflammation Mice Inbred BALB C biology NF-kappa B NF-κB Hematology Molecular biology Triterpenes Up-Regulation Nitric oxide synthase IκBα 030104 developmental biology RAW 264.7 Cells chemistry Cyclooxygenase 2 030220 oncology & carcinogenesis biology.protein Cytokines Boswellic acid Inflammation Mediators Signal Transduction |
| Zdroj: | Cytokine. 107 |
| ISSN: | 1096-0023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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