Mohammad Abohassan1, Mesfer Al Shahrani1, Mohammad Y Alshahrani1, Naseem Begum1, Suresh Radhakrishnan2, Prasanna Rajagopalan3,4. 1. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. 2. Post Graduate and Research Department of Chemistry, Presidency College, Chennai, Tamil Nadu, India. 3. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. prachu.rg@gmail.com. 4. Central Research Laboratory, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. prachu.rg@gmail.com.
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 IC50 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. IC50 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.
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 IC50 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. IC50 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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