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: Gupta S; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicines, India; Inflammation Pharmacology Division, CSIR-Indian Institute of Integrative Medicines, India., Ahsan AU; Cytogenetics Lab, Department of Zoology, Panjab University, Chandigarh, India., Wani A; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicines, India; CancerPharmacology Division, CSIR-Indian Institute of Integrative Medicines, India., Khajuria V; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicines, India; Inflammation Pharmacology Division, CSIR-Indian Institute of Integrative Medicines, India., Nazir LA; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicines, India; PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, India., Sharma S; Natural Product Microbes, CSIR-Indian Institute of Integrative Medicines, India., Bhagat A; Inflammation Pharmacology Division, CSIR-Indian Institute of Integrative Medicines, India., Raj Sharma P; CancerPharmacology Division, CSIR-Indian Institute of Integrative Medicines, India., Bhardwaj S; Department of Pathology, Government Medical College Jammu, India., Peerzada KJ; PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, India., Ali Shah B; Natural Product Microbes, CSIR-Indian Institute of Integrative Medicines, India., Ahmed Z; Inflammation Pharmacology Division, CSIR-Indian Institute of Integrative Medicines, India. Electronic address: zahmed@iiim.ac.in.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2018 Jul; Vol. 107, pp. 93-104. Date of Electronic Publication: 2017 Dec 08.
DOI: 10.1016/j.cyto.2017.12.004
Abstrakt: 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, PGE 2, LTB 4 , 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.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: