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Biologia

pp 1–10 | Cite as

FPX-113 attenuates inflammatory responses by deteriorating cytokines, neutrophil activity and mast cell degranulation via Akt/ NF- κB pathway

  • Prasanna RajagopalanEmail author
  • Ayed A Dera
  • Mohamad Ragab Abdalsamad
  • Majed Al Fayi
  • Abdulrahim Hakami
  • Harish C. Chandramoorthy
Original Article
  • 11 Downloads

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.

Keywords

Arylidene Inflammation Neutrophil Mast cells p-Akt 

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

Notes

Acknowledgments

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).

Compliance with ethical standards

Conflict of interest

The authors hereby state that there is no any conflict of interest related to this study.

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Copyright information

© Institute of Molecular Biology, Slovak Academy of Sciences 2019

Authors and Affiliations

  1. 1.Department of Clinical Laboratory Sciences, College of Applied Medical SciencesKing Khalid UniversityAbhaSaudi Arabia
  2. 2.Central Research Laboratory, College of Applied Medical SciencesKing Khalid UniversityAbhaSaudi Arabia
  3. 3.Research Center of Advanced MaterialsKing Khalid UniversityAbhaSaudi Arabia
  4. 4.Department of Microbiology & Clinical Parasitology and Center for Stem Cell Research, College of MedicineKing Khalid UniversityAbhaSaudi Arabia

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