Polyphenol-rich pomegranate fruit extract (POMx) suppresses PMACI- induced expression of pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-kappaB in human KU812 cells

Comment:  As in the last study, cytokines and chemokines are elevated in chronic fatigue syndrome (CFS) and were recently proposed as a biomarker to diagnose CFS.  Polyphenol-rich pomegranate fruit extract is being proposed as a treatment for inflammatory diseases.

 

Polyphenol-rich pomegranate fruit extract (POMx) suppresses PMACI- induced expression of pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-kappaB in human KU812 cells http://www.journal-inflammation.com/content/pdf/1476-9255-6-1.pdf

Rasheed Z, Akhtar N, Anbazhagan A, Ramamurthy S, Shukla M, Haqqi T
Journal of Inflammation, 2009 6:1 ( 8 January 2009 )

 

Abstract

 

Background Mast cells and basophils are multifunctional effector cells and contain plentiful

secretary granules in their cytoplasm. These cell types are involved in several inflammatory and

immune events and are known to produce an array of mediators including a broad spectrum of

cytokines. Pomegranate fruit is rich in anthocyanins and hydrolysable tannins; a group of

polyphenolic compounds shown to be potent antioxidant with anti-inflammatory activity.

However, no studies have been undertaken to investigate whether a polyphenol-rich pomegranate

fruit extract (POMx) inhibits the inflammatory activity of activated human mast cells and

basophils. The aim of this study was to examine whether POMx modulates inflammatory

reactions using human basophilic cell line KU812.

 

Methods KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus calcium

inophore A23187 (PMACI). The inhibitory effect of POMx on pro-inflammatory cytokine gene

expression and production by stimulated KU812 cells was measured by quantitative RT-PCR,

and cytokine-specific ELISA assays, respectively. Western blotting was used to analyze the

effect of POMx on the activation of mitogen-activated protein kinases (MAPKs), and the nuclear

factor (NF)-κB in PMACI stimulated KU812 cells. Effect on the activity of NF-κB was

determined using Luciferase reporter assay. Significance of differences from control values were

analyzed by means of standard statistical methods.

 

Results POMx significantly decreased PMACI stimulated inflammatory gene expression and

production of interleukin (IL)-6 and IL-8 in KU812 cells. The inhibitory effect of POMx on the

pro-inflammatory cytokines was MAPK subgroups c-jun N-terminal kinase (JNK)- and

extracellular-regulated kinase (ERK) dependent. In addition, POMx suppressed the NF-κB

activation induced by PMACI by inhibiting IκB-degradation in human basophil cells. POMx also

suppressed the powerful induction of NF-κB promoter-mediated luciferase activity in transiently

transfected KU812 cells.

 

Conclusion These novel pharmacological actions of POMx provide new suggestion that POMx

or POMx-derived compounds may be of therapeutic use for the treatment of inflammatory

diseases by suppressing mast cells/basophils activation.