Department of Biotechnology and Animal Science, National Ilan University, Yilan, Taiwan.
Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan.
J Cell Physiol. 2019 Apr;234(4):4081-4094. doi: 10.1002/jcp.27204. Epub 2018 Oct 28.
Dysregulation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in many chronic inflammatory diseases, including gouty arthritis. Activation of the NLRP3 inflammasome requires priming and activation signals: the priming signal controls the expression of NLRP3 and interleukin (IL)-1β precursor (proIL-1β), while the activation signal leads to the assembly of the NLRP3 inflammasome and to caspase-1 activation. Here, we reported the effects of the alcoholic extract of Taiwanese green propolis (TGP) on the NLRP3 inflammasome in vitro and in vivo. TGP inhibited proIL-1β expression by reducing nuclear factor kappa B activation and reactive oxygen species (ROS) production in lipopolysaccharide-activated macrophages. Additionally, TGP also suppressed the activation signal by reducing mitochondrial damage, ROS production, lysosomal rupture, c-Jun N-terminal kinases 1/2 phosphorylation and apoptosis-associated speck-like protein oligomerization. Furthermore, we found that TGP inhibited the NLRP3 inflammasome partially via autophagy induction. In the in vivo mouse model of uric acid crystal-induced peritonitis, TGP attenuated the peritoneal recruitment of neutrophils, and the levels of IL-1β, active caspase-1, IL-6 and monocyte chemoattractant protein-1 in lavage fluids. As a proof of principle, in this study, we purified a known compound, propolin G, from TGP and identified this compound as a potential inhibitor of the NLRP3 inflammasome. Our results indicated that TGP might be useful for ameliorating gouty inflammation via inhibition of the NLRP3 inflammasome.
NACHT、LRR 和 PYD 结构域包含蛋白 3（NLRP3）炎症小体的失调与许多慢性炎症性疾病有关，包括痛风性关节炎。NLRP3 炎症小体的激活需要启动和激活信号：启动信号控制 NLRP3 和白细胞介素（IL）-1β前体（proIL-1β）的表达，而激活信号导致 NLRP3 炎症小体的组装和半胱天冬酶-1 的激活。在这里，我们报道了台湾绿蜂胶（TGP）的酒精提取物在体外和体内对 NLRP3 炎症小体的影响。TGP 通过减少脂多糖激活的巨噬细胞中核因子 kappa B 的激活和活性氧（ROS）的产生来抑制 proIL-1β的表达。此外，TGP 还通过减少线粒体损伤、ROS 产生、溶酶体破裂、c-Jun N 端激酶 1/2 磷酸化和凋亡相关斑点样蛋白寡聚化来抑制激活信号。此外，我们发现 TGP 通过诱导自噬来部分抑制 NLRP3 炎症小体。在尿酸晶体诱导的腹膜炎小鼠模型中，TGP 减轻了腹膜中性粒细胞的募集，以及灌洗液中白细胞介素-1β、活性半胱天冬酶-1、白细胞介素-6 和单核细胞趋化蛋白-1 的水平。作为原理的证明，在这项研究中，我们从 TGP 中纯化了一种已知的化合物，原儿茶酸 G，并鉴定出该化合物是 NLRP3 炎症小体的潜在抑制剂。我们的结果表明，TGP 可能通过抑制 NLRP3 炎症小体对痛风性炎症有治疗作用。
