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Plant derived inhibitors of NF-κB

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Abstract

Plant secondary metabolites (natural products) have been a source for many of our medicines. Their functions in plants remain often unknown, but in recent years there are more and more new compounds isolated and identified and their medicinal potential investigated. The major classes of plant natural products and various derivatives thereof are: phenolics, terpenoids, alkaloids and lignans. The major transcription factor, nuclear factor-κB (NF-κB) is a central downstream regulator of inflammation, cell proliferation and apoptosis that controls the expression of more than 500 genes. It plays an essential role in several aspects of human health including the development of innate and adaptive immunity. The deregulation of NF-κB is associated with many ailments including cancer and chronic inflammatory diseases. In spite of a vast literature describing NF-κB inhibitors from many natural or synthetic sources, such modulators have not been fully tapped for therapeutic purposes and the search for effective and specific inhibitors for therapeutic use and minimal side effects is still relevant and ongoing. Plant-derived phytochemicals are promising lead compounds to develop potent and safe inhibitors for cancer and inflammatory disorders driven by NF-κB. We briefly review the recent knowledge on plant derived phytochemicals and their major NF-κB molecular targets.

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Abbreviations

AMPK:

Adenosine monophosphate- activated protein kinase

AKT:

Protein Kinase B

CBP:

CREB binding protein

COX:

Cyclooxygenase

CXCR CXC:

Chemokine receptor

EGF:

Epidermal growth factor

ERK:

Extracellular signal-regulated kinase

FAK:

Focal adhesion kinase

IAP:

Inhibitor of apoptosis

ICAM:

Intracellular adhesion molecule

IκB:

Inhibitor of NF-κB

IKK:

Inhibitor of NF-κB Kinase

IL-1:

Interleukin-1

LPS:

Lipopolysacharide

MAPK:

Mitogen-activated protein kinase

MMP:

Matrix metalloproteinase

PI3K:

Phosphoinositide 3-kinase

RHD:

REL homology domain

ROS:

Reactive oxygen species

γ-T3:

γ-tocotrienol

TBP:

TATA binding protein

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TNFR:

Tumor necrosis factor receptor

VEGF:

Vascular endothelial factor

XIAP:

X-linked inhibitor of apoptosis protein

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Acknowledgments

The authors gratefully acknowledge the support of the Israel Ministry of Health through the Winkselbaum fund, the Israel Cancer Association through the Miriam and Shlomo Hasid Memorial fund, ICA in Israel, Jacobs foundation through BG-Negev and The Richard H. Holzer Foundation. We thank Janet Ozer (M.Sc.) for assistance in preparation of figure 1 and critical reading of the manuscript.

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Authors and Affiliations

  1. French Associates Institute for Agriculture and Biotechnology of Drylands, Albert Katz Department of Dryland Biotechnologies, The Jacob Blaustein Institutes for Desert Research, Ben Gurion University of the Negev, Sede Boqer Campus, 84990, Midreshet Ben Gurion, Israel

    Avi Golan-Goldhirsh

  2. The Shraga Segal Department of Microbiology and Immunology and Genetics, Faculty of Health Sciences and Laboratory of Oncology, Soroka University Medical Center, Ben Gurion University of the Negev, 84105, Beer Sheva, Israel

    Jacob Gopas

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  1. Avi Golan-Goldhirsh
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Correspondence to Avi Golan-Goldhirsh or Jacob Gopas.

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Golan-Goldhirsh, A., Gopas, J. Plant derived inhibitors of NF-κB. Phytochem Rev 13, 107–121 (2014). https://doi.org/10.1007/s11101-013-9293-5

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