Epigallocatechin-3-gallate inhibition of myeloperoxidase and its counter-regulation by dietary iron and lipocalin 2 in murine model of gut inflammation

Beng San Yeoh, Rodrigo Aguilera Olvera, Vishal Singh, Xia Xiao, Mary J. Kennett, Bina Joe, Joshua D. Lambert, Matam Vijay-Kumar

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Green tea-derived polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been extensively studied for its antioxidant and anti-inflammatory properties in models of inflammatory bowel disease, yet the underlying molecular mechanism is not completely understood. Herein, we demonstrate that EGCG can potently inhibit the proinflammatory enzyme myeloperoxidase in vitro in a dose-dependent manner over a range of physiologic temperatures and pH values. The ability of EGCG to mediate its inhibitory activity is counter-regulated by the presence of iron and lipocalin 2. Spectral analysis indicated that EGCG prevents the peroxidase-catalyzed reaction by reverting the reactive peroxidase heme (compound I:oxoiron) back to its native inactive ferric state, possibly via the exchange of electrons. Further, administration of EGCG to dextran sodium sulfate-induced colitic mice significantly reduced the colonic myeloperoxidase activity and alleviated proinflammatory mediators associated with gut inflammation. However, the efficacy of EGCG against gut inflammation is diminished when orally coadministered with iron. These findings indicate that the ability of EGCG to inhibit myeloperoxidase activity is one of the mechanisms by which it exerts mucoprotective effects and that counter-regulatory factors such as dietary iron and luminal lipocalin 2 should be taken into consideration for optimizing clinical management strategies for inflammatory bowel disease with the use of EGCG treatment.

Original languageEnglish (US)
Pages (from-to)912-926
Number of pages15
JournalAmerican Journal of Pathology
Volume186
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Dietary Iron
Peroxidase
Inflammation
Inflammatory Bowel Diseases
Iron
Dextran Sulfate
Lipocalin-2
epigallocatechin gallate
Polyphenols
Tea
Heme
Anti-Inflammatory Agents
Antioxidants
Electrons
Temperature

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Yeoh, Beng San ; Aguilera Olvera, Rodrigo ; Singh, Vishal ; Xiao, Xia ; Kennett, Mary J. ; Joe, Bina ; Lambert, Joshua D. ; Vijay-Kumar, Matam. / Epigallocatechin-3-gallate inhibition of myeloperoxidase and its counter-regulation by dietary iron and lipocalin 2 in murine model of gut inflammation. In: American Journal of Pathology. 2016 ; Vol. 186, No. 4. pp. 912-926.
@article{a20d77d756bf4167b6d24ae0343720d2,
title = "Epigallocatechin-3-gallate inhibition of myeloperoxidase and its counter-regulation by dietary iron and lipocalin 2 in murine model of gut inflammation",
abstract = "Green tea-derived polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been extensively studied for its antioxidant and anti-inflammatory properties in models of inflammatory bowel disease, yet the underlying molecular mechanism is not completely understood. Herein, we demonstrate that EGCG can potently inhibit the proinflammatory enzyme myeloperoxidase in vitro in a dose-dependent manner over a range of physiologic temperatures and pH values. The ability of EGCG to mediate its inhibitory activity is counter-regulated by the presence of iron and lipocalin 2. Spectral analysis indicated that EGCG prevents the peroxidase-catalyzed reaction by reverting the reactive peroxidase heme (compound I:oxoiron) back to its native inactive ferric state, possibly via the exchange of electrons. Further, administration of EGCG to dextran sodium sulfate-induced colitic mice significantly reduced the colonic myeloperoxidase activity and alleviated proinflammatory mediators associated with gut inflammation. However, the efficacy of EGCG against gut inflammation is diminished when orally coadministered with iron. These findings indicate that the ability of EGCG to inhibit myeloperoxidase activity is one of the mechanisms by which it exerts mucoprotective effects and that counter-regulatory factors such as dietary iron and luminal lipocalin 2 should be taken into consideration for optimizing clinical management strategies for inflammatory bowel disease with the use of EGCG treatment.",
author = "Yeoh, {Beng San} and {Aguilera Olvera}, Rodrigo and Vishal Singh and Xia Xiao and Kennett, {Mary J.} and Bina Joe and Lambert, {Joshua D.} and Matam Vijay-Kumar",
year = "2016",
month = "4",
day = "1",
doi = "10.1016/j.ajpath.2015.12.004",
language = "English (US)",
volume = "186",
pages = "912--926",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "4",

}

Epigallocatechin-3-gallate inhibition of myeloperoxidase and its counter-regulation by dietary iron and lipocalin 2 in murine model of gut inflammation. / Yeoh, Beng San; Aguilera Olvera, Rodrigo; Singh, Vishal; Xiao, Xia; Kennett, Mary J.; Joe, Bina; Lambert, Joshua D.; Vijay-Kumar, Matam.

In: American Journal of Pathology, Vol. 186, No. 4, 01.04.2016, p. 912-926.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Epigallocatechin-3-gallate inhibition of myeloperoxidase and its counter-regulation by dietary iron and lipocalin 2 in murine model of gut inflammation

AU - Yeoh, Beng San

AU - Aguilera Olvera, Rodrigo

AU - Singh, Vishal

AU - Xiao, Xia

AU - Kennett, Mary J.

AU - Joe, Bina

AU - Lambert, Joshua D.

AU - Vijay-Kumar, Matam

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Green tea-derived polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been extensively studied for its antioxidant and anti-inflammatory properties in models of inflammatory bowel disease, yet the underlying molecular mechanism is not completely understood. Herein, we demonstrate that EGCG can potently inhibit the proinflammatory enzyme myeloperoxidase in vitro in a dose-dependent manner over a range of physiologic temperatures and pH values. The ability of EGCG to mediate its inhibitory activity is counter-regulated by the presence of iron and lipocalin 2. Spectral analysis indicated that EGCG prevents the peroxidase-catalyzed reaction by reverting the reactive peroxidase heme (compound I:oxoiron) back to its native inactive ferric state, possibly via the exchange of electrons. Further, administration of EGCG to dextran sodium sulfate-induced colitic mice significantly reduced the colonic myeloperoxidase activity and alleviated proinflammatory mediators associated with gut inflammation. However, the efficacy of EGCG against gut inflammation is diminished when orally coadministered with iron. These findings indicate that the ability of EGCG to inhibit myeloperoxidase activity is one of the mechanisms by which it exerts mucoprotective effects and that counter-regulatory factors such as dietary iron and luminal lipocalin 2 should be taken into consideration for optimizing clinical management strategies for inflammatory bowel disease with the use of EGCG treatment.

AB - Green tea-derived polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been extensively studied for its antioxidant and anti-inflammatory properties in models of inflammatory bowel disease, yet the underlying molecular mechanism is not completely understood. Herein, we demonstrate that EGCG can potently inhibit the proinflammatory enzyme myeloperoxidase in vitro in a dose-dependent manner over a range of physiologic temperatures and pH values. The ability of EGCG to mediate its inhibitory activity is counter-regulated by the presence of iron and lipocalin 2. Spectral analysis indicated that EGCG prevents the peroxidase-catalyzed reaction by reverting the reactive peroxidase heme (compound I:oxoiron) back to its native inactive ferric state, possibly via the exchange of electrons. Further, administration of EGCG to dextran sodium sulfate-induced colitic mice significantly reduced the colonic myeloperoxidase activity and alleviated proinflammatory mediators associated with gut inflammation. However, the efficacy of EGCG against gut inflammation is diminished when orally coadministered with iron. These findings indicate that the ability of EGCG to inhibit myeloperoxidase activity is one of the mechanisms by which it exerts mucoprotective effects and that counter-regulatory factors such as dietary iron and luminal lipocalin 2 should be taken into consideration for optimizing clinical management strategies for inflammatory bowel disease with the use of EGCG treatment.

UR - http://www.scopus.com/inward/record.url?scp=84960984370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960984370&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2015.12.004

DO - 10.1016/j.ajpath.2015.12.004

M3 - Article

C2 - 26968114

AN - SCOPUS:84960984370

VL - 186

SP - 912

EP - 926

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 4

ER -