Abstract
Search of novel chemical compounds to manage disorders of inflammation is always on demand. Herein we report FPX-113 a novel small molecule to exhibit excellent anti-inflammatory properties in human whole blood (HWB), peripheral blood mononuclear cells (PBMCs), RBL-2H3 and THP-1 cells. FPX-113 showed an inhibition of TNF-α, IFN-γ, IL-2, IL-6, IL-8 and IL-17 release from HWB and PBMC with IC50 values of 364.6 nM, 505.2 nM, 160.2 nM, 369.1 nM 371.2 nM, 459 nM and 64.14 nM, 92.30 nM, 49.88 nM, 151.7 nM, 108.9 nM, 92.70 nM respectively. The compound inhibited neutrophil migration and elastase in a dose dependent way. Further, FPX-113 inhibited the degranulation of rat mast cell basophils in RBL-2H3 cells with an IC50 of 280.5 nM. A dose dependent inhibition of Akt phosphorylation in RBL-2H3 and THP-1 cells and down regulation of NF- κB in PBMCs, RBL-2H3 and THP-1 cells by FPX-113 were evidenced when induced with 5 μg/mL PHA + 50 ng/mL PMA for 30 min. Taken together, the results suggest FPX-113 exhibits anti-inflammatory mechanism signaled via Akt/ NF- κB pathway. These findings will provide a wide scope for FPX-113 and its close analogues to be developed as novel anti-inflammatory agents for various diseases.
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Abbreviations
- ACD:
-
Acid citrate dextrose
- ATCC:
-
American Type Culture Collection
- DMSO:
-
Dimethyl sulphoxide
- DNP-BSA:
-
2,4-Dinitrophenol- Bovine serum albumin
- ELISA:
-
Enzyme linked immune sorbent assay
- FBS:
-
Fetal bovine serum
- fMLP:
-
N-Formyl methionyl-leucyl-phenylalanine
- HBSS:
-
Hanke’s Buffered Salt Solution
- HWB:
-
Human whole blood
- IFN-γ:
-
Interferon gamma
- IgE:
-
Immunoglobin E
- IL:
-
Interleukin
- Kcl,:
-
Potassium chloride
- MTT:
-
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
- NCE:
-
Novel chemical entity
- PBMC:
-
Peripheral blood mono nucleocytes
- PHA:
-
Phytohaemagglutinin
- PMA:
-
Phorbol-12-myristate-13-acetate
- RBL:
-
Rat basophilic leukemia
- SDS:
-
Sodium dodecyl sulphate
- TBS:
-
Tris buffer saline
- TNF-α:
-
Tissue necrosis factor alpha
- μM:
-
Micro molar
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The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University, Abha, Saudi Arabia, for funding this work through General Research Project under grant number (G.R.P.1/80/40).
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Rajagopalan, P., A Dera, A., Abdalsamad, M.R. et al. FPX-113 attenuates inflammatory responses by deteriorating cytokines, neutrophil activity and mast cell degranulation via Akt/ NF- κB pathway. Biologia 75, 447–456 (2020). https://doi.org/10.2478/s11756-019-00367-z
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DOI: https://doi.org/10.2478/s11756-019-00367-z