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- Title
Epigallocatechin-3-Gallate Prevents Acute Gout by Suppressing NLRP3 Inflammasome Activation and Mitochondrial DNA Synthesis.
- Authors
Lee, Hye Eun; Yang, Gabsik; Park, Youn Bum; Kang, Han Chang; Cho, Yong-Yeon; Lee, Hye Suk; Lee, Joo Young; Atanasov, Atanas G.; Šmejkal, Karel; Heiss, Elke
- Abstract
Gout is a chronic inflammatory disease evoked by the deposition of monosodium urate (MSU) crystals in joint tissues. The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is responsible for the gout inflammatory symptoms induced by MSU crystals. We investigated whether epigallocatechin-3-gallate (EGCG) suppresses the activation of the NLRP3 inflammasome, thereby effectively preventing gouty inflammation. EGCG blocked MSU crystal-induced production of caspase-1(p10) and interleukin-1β in primary mouse macrophages, indicating its suppressive effect on the NLRP3 inflammasome. In an acute gout mouse model, oral administration of EGCG to mice effectively alleviated gout inflammatory symptoms in mouse foot tissue injected with MSU crystals. The in vivo suppressive effects of EGCG correlated well with the suppression of the NLRP3 inflammasome in mouse foot tissue. EGCG inhibited the de novo synthesis of mitochondrial DNA as well as the production of reactive oxygen species in primary mouse macrophages, contributing to the suppression of the NLRP3 inflammasome. These results show that EGCG suppresses the activation of the NLRP3 inflammasome in macrophages via the blockade of mitochondrial DNA synthesis, contributing to the prevention of gouty inflammation. The inhibitory effects of EGCG on the NLRP3 inflammasome make EGCG a promising therapeutic option for NLRP3-dependent diseases such as gout.
- Subjects
DNA synthesis; MITOCHONDRIAL DNA; EPIGALLOCATECHIN gallate; NLRP3 protein; GOUT; REACTIVE oxygen species; MACROPHAGES
- Publication
Molecules, 2019, Vol 24, Issue 11, p2138
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules24112138