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Phytochemicals as a potential source for TNF-α inhibitors

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Abstract

Cytokines play an important role in the immune system. Any disorder in the regulation of cytokines can lead to the development of inflammatory diseases. Tumor necrosis factor-α (TNF-α) is one of the most important inflammatory cytokines that controls different types of cell functions. The overproduction of TNF-α is linked with the development of various diseases such as asthma, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, septic shock, diabetes and atherosclerosis. Plants are considered as excellent sources of pharmacologically active compounds. Currently, scientists are searching for natural products with anti-TNF-α properties for the treatment of various inflammatory disorders. At present, protein-based drugs are available for the inhibition of TNF-α, however these have some limitations. Plant might provide an alternative and cost-effective source of drugs that can regulate TNF-α levels. This review briefly highlights the physiological and pathological roles of TNF-α along with a description of plant-derived compounds capable of interfering with TNF-α activity and production.

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Abbreviations

AKT:

A serine/threonine kinase

AP-1:

Activator protein-1

COX-2:

Cycloxygenase 2

DD:

Death domain

EGB-761:

Extract of Ginkgo biloba

ERK:

Extracellular signal-regulated kinases

ICAM-1:

Intercellular adhesion molecule-1

IGF:

Insuline-like growth factor

IκB:

Inhibitor of nuclear factor-kappa B

INOS:

Inducible nitric oxide

IRA:

Insulin receptor activation

LOX-2:

Lipoxygenase-2

LPS:

Lipopolysaccharides

MAPK:

Mitogen activated protein kinase

MCP-1:

Monocyte chemoattractant protein 1

MEKK1:

Mitogen-activated protein kinase kinase 1

NF-κB:

Nuclear factor kappa B

NIK:

Nuclear factor-kB-inducing kinase

NO:

Nitric oxide

PDE4:

Phosphodiesterase 4

PGE2:

Prostaglandin E2

PK:

Protein kinase

RAW-264.7:

Rat leukemia monocyte macrophage cell line

RBL-2H3:

Rat basophilic leukemia mast cell line

RIP:

Receptor activating protein

TACE:

TNF-α converting enzyme

TNF-α:

Tumor necrosis factor alpha

VCAM-1:

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

ZZ-CWE:

Crude water extract of Zingiber zerumbet

NF-κB:

A protein complex which is found in all animal cells and is actively involved in regulating immune response to infection

T cells:

They belong to a group of white blood cells known as lymphocytes, and play a central role in cell mediated immunity

NK cells:

(Natural killer cells), these are lymphocytes and they are considered as a major component of the immune system

B cells:

These are lymphocytes that play a large role in the humoral immune response

IL-1α and β:

These are pro-inflammatory cytokines involved in immune defense against infection

IC50:

Half maximal inhibitory concentration: is a measure of effectiveness of a compound in inhibiting a biological function

IFN-γ:

Interferon-gamma; a soluble cytokine that is important for innate and adaptive immunity against viral and intracellular bacterial infections

TNF-α:

(Tumor necrosis factor alpha) is a pro inflammatory cytokine involved in the process of inflammation. It is produced by several types of cells but especially macrophages

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Acknowledgments

The authors gratefully acknowledge the Higher Education Commission (HEC) of Pakistan & Smart Mix Programme of the Netherlands Ministry of Economic Affairs and the Netherlands Ministry of Education, Culture and Science for the support of Muzamal Iqbal.

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Authors and Affiliations

  1. Natural Products Laboratory, Institute of Biology, Leiden University, Einsteinweg 55, P.O. Box 9502, 2300 RA, Leiden, The Netherlands

    Muzamal Iqbal, Robert Verpoorte & Natali Rianika Mustafa

  2. Fytagoras B.V., Sylviusweg 72, 2333 BE, Leiden, The Netherlands

    Henrie A. A. J. Korthout

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  1. Muzamal Iqbal
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  2. Robert Verpoorte
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  3. Henrie A. A. J. Korthout
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  4. Natali Rianika Mustafa
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Correspondence to Natali Rianika Mustafa.

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Iqbal, M., Verpoorte, R., Korthout, H.A.A.J. et al. Phytochemicals as a potential source for TNF-α inhibitors. Phytochem Rev 12, 65–93 (2013). https://doi.org/10.1007/s11101-012-9251-7

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  • DOI: https://doi.org/10.1007/s11101-012-9251-7

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