FNF-12, a Novel Benzylidene-chromanone Derivative, Attenuates Inflammatory Response in in Vitro and in Vivo Asthma Models Mediated by M2-related Th2 Cytokines Via MAPK and NF-kB Signaling

Overview

Journal Pharmacol Rep

Specialty Pharmacology

Date 2021 Sep 1

PMID 34468975

Citations 5

Authors

Mohammad Abohassan

Mesfer Al Shahrani

Mohammad Y Alshahrani

Naseem Begum

Suresh Radhakrishnan

Prasanna Rajagopalan

Affiliations

Soon will be listed here.

Abstract

Background And Aim: This study evaluates a novel benzylidene-chromanone derivative, FNF-12, for efficacy in in vitro and in vivo asthma models.

Methods: Rat basophilic leukemia (RBL-2H3) and acute monocytic leukemia (THP-1)-derived M2 macrophages were used. Human whole blood-derived neutrophils and basophils were employed. Flow cytometry was used for studying key signalling proteins. Platelet activation factor (PAF)-induced asthma model in guinea pigs was used for in vivo studies.

Results: The chemical structure of FNF-12 was confirmed with proton-nuclear mass resonance (NMR) and mass spectroscopy. FNF-12 controlled degranulation in RBL-2H3 cells with an IC value of 123.7 nM and inhibited TNF-α release from these cells in a dose-responsive way. The compound effectively controlled the migration and elastase release in activated neutrophils. IC value in the FcεRI-basophil activation assay was found to be 205 nM. FNF-12 controlled the release of lipopolysaccharide (LPS)-induced interleukin-10, I-309/CCL1 and MDC/CCL22 in THP-1 derived M2 macrophages. The compound suppressed LPS-induced mitogen activated protein kinase (MAPK)-p-p38 and nuclear factor kappa B(NF-kB)-p-p65 expression in these cells. A dose-dependent decrease in the accumulation of total leucocytes, eosinophils, neutrophils and macrophages was observed in PAF-induced animal models.

Conclusion: FNF-12 was able to control the inflammatory responses in in vitro and in vivo asthma models, which may be driven by controlling M2-related Th2 cytokines via MAPK and NF-kB signaling.

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