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Curcumin: An NF- k B and Multiple Pathway
Signaling Inhibitor


Curcumin, the active ingredient of the spice turmeric, is a highly pleiotropic, complex  molecule which interacts with a number of signaling targets involved in inflammation and other biological processes. Many signaling molecules ultimately signal through NF-
k B, and whereas many pharmacological activities have been ascribed to curcumin, the inhibition of NF- k B signaling has been a key focus.   In this regard, data from IMGENEX’s laboratories, as well as from other model systems in the scientific literature, provide supporting evidence for curcumin as an extremely powerful research tool for inhibiting NF- k B activation.

NF-
k B is a ubiquitous eukaryotic transcription factor that plays a key role in regulating a number of cellular processes including inflammation, cellular proliferation, transformation and tumorigenesis.  In unstimulated cells, NF- k B dimers are held in the cytoplasm by I k Bs which mask the nuclear localization signals (NLS) of NF- k B  required for nuclear translocation and activation. Following cell stimulation, I k B a is phosphorylated and degraded. This results in NLS exposure, thereby enabling NF- k B to translocate to the nucleus and activate transcription. Evidence suggests that curcumin suppresses NF- k B activation and subsequent proinflammatory gene expression by blocking I k B phosphorylation.

Curcumin (Cat. No. IMG-2010) is a highly purified extract from the turmeric plant Curcuma longa especially designed for research use. Our curcumin is assay validated, and for a limited time only, we are offering a complimentary vial with the purchase of any TLR/NF- k B Pathway Inhibitor or Cell Line, or NF- k B Readout Assay Kit.

References:
1. Curcumin as a therapeutic agent: The evidence from in vitro, animal and human studies. Epstein J, IR Sanderson, and TT Macdonald. B J Nutrition. doi:10.1017/S0007114509993667 (2009).
2. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research. Jurenka JS. Alternative Medicine Review 2:141153 (2009).

Curcumin inhibition of ligand activated TLR/NF- k B signaling.  TLR5/NF- k B/SEAPorter HEK 293 (IML-105) cells were plated in 12-well plates (0.5 x 106 cells/well)  for 16 h. Cells were preincubated with increasing concentrations of curcumin (IMG-2010) for 2 h or a DMS0 vehicle (V) control. Cells were then stimulated with the TLR5 ligand Flagellin (10 ng/ml, IMG-2205) for 24 h. The SEAPorter Assay Kit (10055K) was used to measure SEAP, the readout assay for measuring NF- k B activation in TLR5/NF- k B cells. The results show that the cells had  a minimal basal level of NF- k B activity which was dramatically increased by Flagellin. They also show that curcumin decreased Flagellin-activated NF- k B signaling in a dose-dependent manner.

TLR Ligands

Pam3CSK4

Imiquimod

Poly(I).Poly(C)

Imidazoquinoline Resiquimod (R-848)

LPS from E. Coli

CpG ODN (2006) with negative control oligo (human)

Flagellin, Recombinant

CpG ODN (1668) with negative control oligo (mouse)

MALP-2

 

TLR and NF- k B Inhibitors

IKKg NEMO Binding Domain (NBD)

TRAF6

NF-kB p65 (Ser276)

MyD88 Homodimerization

NF-kB p65 (Ser529/536)

TIRAP

NF-kB p50 (NLS)

 

Stable Reporter Cell Lines

TLR/NF- k B/SEAPorter™ HEK 293

TLR/HEK 293
 

ACTIVELISA™ Kits

NF- k B/p65 ActivELISA Kit

Phospho-I k B a ActivELISA Kit