BK21 Plus, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea.
Molecules. 2019 Jun 6;24(11):2138. doi: 10.3390/molecules24112138.
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 suppressive effects of EGCG correlated well with the suppression of the NLRP3 inflammasome in mouse foot tissue. EGCG inhibited the 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.
痛风是一种由单钠尿酸盐（MSU）晶体在关节组织中沉积引起的慢性炎症性疾病。核苷酸结合寡聚化结构域（NOD）样受体（NLR）家族包含 pyrin 结构域的 3 （NLRP3）炎性小体负责由 MSU 晶体引起的痛风炎症症状。我们研究了表没食子儿茶素没食子酸酯（EGCG）是否抑制 NLRP3 炎性小体的激活，从而有效预防痛风炎症。EGCG 阻断了原代小鼠巨噬细胞中 MSU 晶体诱导的半胱天冬酶-1（p10）和白细胞介素-1β的产生，表明其对 NLRP3 炎性小体具有抑制作用。在急性痛风小鼠模型中，EGCG 口服给药可有效缓解 MSU 晶体注射入小鼠足部组织引起的痛风炎症症状。EGCG 的抑制作用与在小鼠足部组织中对 NLRP3 炎性小体的抑制作用密切相关。EGCG 抑制了原代小鼠巨噬细胞中线粒体 DNA 的合成以及活性氧的产生，从而抑制了 NLRP3 炎性小体的激活。这些结果表明，EGCG 通过抑制线粒体 DNA 的合成来抑制巨噬细胞中 NLRP3 炎性小体的激活，从而有助于预防痛风炎症。EGCG 对 NLRP3 炎性小体的抑制作用使 EGCG 成为 NLRP3 依赖性疾病（如痛风）的一种有前途的治疗选择。
