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Green tea catechins suppress NF-κB-mediated inflammatory responses: relevance to nutritional management of inflammation

Published online by Cambridge University Press:  27 January 2011

Naren H. Ravindranath  and
Mepur H. Ravindranath
Naren H. Ravindranath
Affiliation:
Department of Biomedical Sciences, Norris Dental Science Center, Herman Ostrow School of Dentistry, University of Southern California, 925 W 34th Street, Den 4110B, Los Angeles, CA90089, USA email [email protected]
Mepur H. Ravindranath
Affiliation:
Terasaki Foundation Laboratory, 11570 West Olympic Boulevard, Los Angeles, CA90064, USA emails [email protected]; [email protected]
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Abstract

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Type
Invited Commentary
Information
British Journal of Nutrition , Volume 105 , Issue 12 , 28 June 2011 , pp. 1715 - 1717
Copyright
Copyright © The Authors 2011

Blood loss after trauma induces several systemic inflammatory responses culminating in the dysfunction and failure of organs. In this issue of the British Journal of Nutrition, Relja et al. (Reference Relja, Töttel and Breig1) have examined the inflammatory signals at the subcellular, cellular and tissue levels after haemorrhage-induced hepatic injury and resuscitation in rats. Hepatic injury and resuscitation induced the expression of intercellular adhesion molecule-1, neutrophil infiltration and necrosis in the liver, and augmented serum alanine transaminase and IL-6 levels. It also induced IκBα phosphorylation and the activation of NF-κB. Pre-treatment with green tea extract (GTE: catechins >80 %, with >40 % of epigallocatechin gallate (EGCG)) suppressed the inflammatory responses at all levels, including neutrophil infiltration, intercellular adhesion molecule-1 expression and the release of IL-6, and, importantly, suppressed the activation of NF-κB.

The inflammatory responses occurring in the liver after haemorrhage are parallel to the inflammatory events occurring after inducing ischaemia, and EGCG is also active in the latter setting(Reference Giakoustidis, Giakoustidis and Iliadis2–Reference Ichikawa, Matsui and Imai5). The anti-inflammatory efficacy of EGCG demonstrated in all these studies generates a unifying hypothesis. Hepatic injury induced by ischaemia(Reference Giakoustidis, Giakoustidis and Iliadis2) caused oxidative stress with enhanced production of reactive oxygen species and TNF-α; both mediated the expression of nuclear factors and kinases, activating the signal transduction pathways to trigger cell death. The liver that stained positive for NF-κB in the ischaemia group remained negative in the EGCG-pre-treated group. Neutrophil infiltration that was enhanced in the ischaemia group was significantly reduced after EGCG. Ischaemia-induced myocardial injury(Reference Aneja, Hake and Burroughs3) also caused significant neutrophil infiltration, an increase in plasma IL-6, and activation of IκB kinase and NF-κB in the tissues. EGCG pre-treatment significantly reduced myocardial damage, neutrophil infiltration and plasma IL-6, and also suppressed the NF-κB pathway. Intestinal injury induced by ischaemia(Reference Giakoustidis, Giakoustidis and Koliakou4) also resulted in an enhanced production of reactive oxygen species, neutrophil infiltration and activation of NF-κB. EGCG pre-treatment significantly deactivated NF-κB, decreased neutrophil infiltration and lowered reactive oxygen species production. All these studies support the conclusion derived by Relja et al. and collectively point out that induced inflammatory responses are mediated through NF-κB-dependent mechanisms, and EGCG per se or in combination with other catechins suppresses NF-κB activation and alleviates inflammation.

There are enumerable reports on the efficacy of EGCG per se or EGCG in combination with other catechins (epigallocatechin or epicatechin gallate or gallocatechin gallate)(Reference Ichikawa, Matsui and Imai5–Reference Ludwig, Lorenz and Grimbo9) on inflammatory responses induced by different exogenous and endogenous factors. The inflammatory inducers include polymicrobial sepsis(Reference Wheeler, Lahni and Hake10), lipopolysaccharide(Reference Ichikawa, Matsui and Imai5–Reference Yang, Oz and Barve7, Reference Yang, de Villiers and McClain11), Staphylococcus aureus enterotoxin B(Reference Watson, Vicario and Wang12), Helicobacter pylori infection(Reference Lee, Yeo and Choue13), IL-1β alone(Reference Corps, Curry and Buttle8, Reference Singh, Ahmed and Islam14–Reference Wheeler, Catravas and Odoms16) or in combination with β-amyloid(Reference Kim, Jeong and Lee17) or oxygen tension(Reference Andriamanalijaona, Kypriotou and Baugé18) or TNF-α(Reference Ludwig, Lorenz and Grimbo9, Reference Heinecke, Grzanna and Au19) or TNF-α alone(Reference Chen, Wheeler and Malhotra20–Reference Lee, Jung and Kim22), UV-B(Reference Afaq, Adhami and Ahmad23–Reference Song, Bi and Xu25), repetitive oxidative stress(Reference Sen, Chakraborty and Raha26), cigarette smoke condensate(Reference Syed, Afaq and Kweon27), phorbol 12-myristate 13-acetate(Reference Shin, Kim and Jeong28–Reference Kundu and Surh30), trinitrobenenesulphonic acid(Reference Abboud, Hake and Burroughs31)- or acetic acid(Reference Ran, Chen and Xiao32)-induced colitis, receptor activator for the NF-κB ligand(Reference Lin, Chen and Wang33, Reference Lee, Jin and Shim34) or high glucose(Reference Wu, Wu and Huang35). Most importantly, all these studies document that consequent to the down-regulation of NF-κB pathways, EGCG or catechin combination suppressed the levels of several pro-inflammatory cytokines (TNF-α(Reference Yang, de Villiers and McClain11, Reference Watson, Vicario and Wang12, Reference Shin, Kim and Jeong28, Reference Ran, Chen and Xiao32, Reference Wu, Wu and Huang35) IL-6(Reference Kim, Jeong and Lee17, Reference Xia, Song and Bi24, Reference Shin, Kim and Jeong28), IL-8(Reference Wheeler, Catravas and Odoms16, Reference Kim, Jeong and Lee17, Reference Chen, Wheeler and Malhotra20, Reference Syed, Afaq and Kweon27, Reference Shin, Kim and Jeong28), interferon-γ(Reference Watson, Vicario and Wang12, Reference Ran, Chen and Xiao32)), chemokine (Fractalkine(Reference Lee, Jung and Kim22)) and enzymes (matrix metaloproteinases-1, -3, -9(Reference Syed, Afaq and Kweon27), -13(Reference Corps, Curry and Buttle8, Reference Ahmed, Wang and Lalonde15, Reference Andriamanalijaona, Kypriotou and Baugé18), NO synthase(Reference Lin and Lin6, Reference Wheeler, Lahni and Hake10, Reference Singh, Ahmed and Islam14, Reference Song, Bi and Xu25, Reference Syed, Afaq and Kweon27, Reference Ran, Chen and Xiao32); cyclo-oxygenase-2(Reference Kim, Jeong and Lee17, Reference Heinecke, Grzanna and Au19, Reference Kundu and Surh30), glucosyl/lactosyl and Gb3 transferases(Reference Moon, Choi and Lee21)), growth factors (vascular endothelial growth factor(Reference Kim, Jeong and Lee17)), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin(Reference Ludwig, Lorenz and Grimbo9)) and monocyte chemotactic protein-1(Reference Hong, Kim and Chang29). In this regard, the study of Relja et al. is well justified in the use of GTE, since other tea catechins act synergistically with EGCG. It is important to use GTE with a greater percentage of EGCG to counteract inflammation. These preclinical studies on the induced inflammatory responses promote the hypothesis that green tea catechins have the potential to suppress the NF-κB-mediated inflammatory pathway into a salient concept relevant to nutritional management of inflammation. The emerging concept is that EGCG or GTE has the potential to block the NF-κB pathway, which plays a critical role in inflammation induced by various factors and also in malignancy. These aforementioned studies pave the way for phase I and II clinical trials using GTE or EGCG to control trauma, haemorrhage or ischaemia-induced inflammation.

There is no conflict of interest.

References

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