Beneficial Properties of Phytochemicals on NLRP3 Inflammasome

Jan 2, 2018 - Gouty arthritis is characterized by the precipitation of monosodium urate (MSU) crystals in the joint. Pro-inflammatory cytokine IL-1β ...
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Beneficial properties of phytochemicals on NLRP3 inflammasome-mediated gout and complication Jhih-Jia Jhang, Jia-Hong Lin, and Gow-Chin Yen J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.7b05113 • Publication Date (Web): 02 Jan 2018 Downloaded from http://pubs.acs.org on January 3, 2018

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Journal of Agricultural and Food Chemistry is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

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Journal of Agricultural and Food Chemistry

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Beneficial properties of phytochemicals on NLRP3

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inflammasome-mediated gout and complication

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Jhih-Jia Jhang†, Jia-Hong Lin†, and Gow-Chin Yen †,‡,*

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University, 145 Xingda Road, Taichung 40227, Taiwan

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Xingda Road, Taichung 40227, Taiwan

Department of Food Science and Biotechnology, National Chung Hsing

Graduate Institute of Food Safety, National Chung Hsing University, 145

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*Author to whom correspondence should be addressed.

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Tel: 886-4-2287-9755, Fax: 886-4-2285-4378,

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E-Mail: [email protected]

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Keywords: gout; monosodium urate; IL-1β; NLRP3; phytochemicals

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Abbreviations:

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CARD, caspase recruitment domains; DAMPs danger-associated molecular patterns;

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EGCG, epigallocatechin gallate; IL-1β, interleukin-1β; LPS, lipopolysaccharide; LRR,

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leucine-rich repeat; MSU, monosodium urate; MtROS, mitochondrial reactive oxygen

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species; NF-κB, nuclear factor-κB; NLRP3, nucleotide-binding oligomerization

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domain-like receptor containing pyrin domain 3; NLRs, nucleotide-binding domain

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leucine-rich

repeat

(LRR)-containing

receptors;

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NSAIDs,

nonsteroidal

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anti-inflammatory drugs; PAMPs, pathogen-associated molecular patterns; PGE2,

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prostaglandin E2; PRRs, pattern recognition receptors; ROS, reactive oxygen species;

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STZ, streptomycin; TNF-α, tumor necrosis factor-α; TRX, thioredoxin; TXNIP,

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thioredoxin interaction protein

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Abstract

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Gouty arthritis is characterized by the precipitation of monosodium urate (MSU)

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crystals in the joint. Pro-inflammatory cytokine IL-1β is a critical manifestation in

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response to MSU crystals attack. IL-1β secretion is dependent on the

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nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3

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(NLRP3) inflammasome. Abnormal activation of the NLRP inflammasome is related

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to cellular oxidative stress. However, recent studies have illustrated that

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phytochemicals with potent antioxidant activity exert inhibitory effects on NLRP3

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inflammasome-mediated diseases. This review focuses on the current findings of

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studies on the NLRP3 inflammasome and the proposed mechanisms that MSU

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crystals trigger inflammation via activation of the NLRP3 inflammasome. We also

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summarized the potential use of phytochemicals on NLRP3 inflammasome-mediated

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diseases, suggesting that phytochemicals can further prevent acute gout attack.

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INTRODUCTION

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Gout is usually characterized as an elevation of serum uric acid and

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crystallization of monosodium urate (MSU) 1. MSU crystals are needle-shaped and

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aggregate as tophi in and around joints, soft tissues, and various organs 2. The

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deposition of MSU crystals in joints further triggers inflammatory responses, known

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as gouty inflammation. Gouty inflammation can occur in bursae, tendons, and joints.

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The first gout flare predominately occurs in the large joint of the big toe (the first

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metatarsophalangeal). In addition, foot, knee, elbow, and hand are common attack

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locations 1-2.

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MSU crystals induces inflammation by activation of the complement system and

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recruits mast cells, neutrophils, and monocyte cells that infiltrate the joint tissue,

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causing cartilage and synovial tissue damage 1-2. In addition, the secretion of IL-1β, a

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pro-inflammatory cytokine, is the main clinical manifestation of an early gout attack

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complex called the nucleotide-binding oligomerization domain-like receptor pyrin

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domain containing 3 (NLRP3, also known as NALP3 or cryopyrin) inflammasome 5.

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Redox signaling molecules, such as reactive oxygen species (ROS), mediate NLRP3

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inflammasome activation, while ROS inhibitors suppress NLRP3 inflammasome-

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mediated inflammation

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inflammasome activation

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supplementation of vitamin C can decrease the risk of gout

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consumption and cherry extracts can decrease risk of recurrent gout attacks

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pre-clinical study first demonstrated that the phytochemical epigallocatechin gallate

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(EGCG) is a ROS scavenger as well as an inflammasome suppressor 13. In this review,

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we attempted to elucidate the cellular and molecular mechanisms of the

. MSU crystals trigger the maturation of IL-1β via the recruitment of a cytosolic

, indicating the vital role of oxidative stress on . Previous studies showed that daily coffee intake and

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, and cherry fruit 12

. A

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inflammasome activation in gout. In addition, previous studies have illustrated that

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phytochemicals with antioxidant properties can reduce inflammatory responses via the

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modulation of inflammasome activity

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promoting anti-inflammasome activity is also discussed.

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. The usefulness of phytochemicals for

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HYPERURICEMIA AND GOUT Uric acid is a metabolite of purine metabolism through xanthine oxidase enzyme 15

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converting hypoxanthine and xanthine

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which converts urate into the more soluble and easily excreted allantoin 15. The lack

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of a functional uricase gene in Homo sapiens during evolution has resulted in the

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accumulation of urate levels in blood. Approximately one-third of the urate level

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inside the body is eliminated through the gastrointestinal tract, with the remainder

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excreted in the urine. The levels of normal plasma urate are between 200 and 410

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µmol/L (3.3 to 6.9 mg/dL), and urate has a maximum solubility of 420 µmol/L (7

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mg/dL), approximately

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which is defined by blood urate level over 7 mg/dL 17. Hyperuricemia has a primary

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role in complications, such as gout, hypertension, chronic kidney disease, and

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metabolic syndrome 17-18.

. Most mammalian species express uricase,

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. Over-production of urate is the cause of hyperuricemia,

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Gout attack is triggered by the precipitation of MSU crystals in the joints. The

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presence of MSU crystals is characteristic of gouty arthritis 19. A study demonstrated

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that large needle-shape crystals of urate specifically existed in the synovial fluid in

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gouty patients, which is different from other types of arthritis, such as rheumatic

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arthritis patients and osteoarthritis

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populations have a higher prevalence of gout compared to other areas of the world 20.

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Particularly, the prevalence of gout in Oceanic populations within ethnic groups, such

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. People in developed countries and in Oceanic

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as Taiwanese aboriginals and Maori, is over 10%. From seven representative

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countries, the age-specific prevalence of gout is similar in the USA, New Zealand,

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UK, and Netherlands. Taiwan has a higher prevalence of gout in all age strata,

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whereas South Korea has the lowest age-specific prevalence

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was observed from Nutrition and Health Surveys in Taiwan (NAHSIT) 1993-1996 to

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NAHSIT 2005-2008 in gout prevalence (4.74%→8.21% in men, p