Gout, the most prevalent inflammatory arthritis worldwide, released interleukin-1β (IL-1β) and Cathepsin B inflammatory mediators that constitute the hallmark of the disease. Herein we aimed to investigate whether procyanidin B2 (PCB2), a natural dietary compound, can suppress MSU crystals-stimulated gouty inflammation. Treated with lipopolysaccharide (LPS) plus MSU, both mouse peritoneal macrophages (MPM) and mouse bone marrow-derived macrophages (BMDM) released a large amount of mature IL-1β compared to those treated with MSU or LPS alone, while IL-1β release was blocked by TLR4 and its downstream effector inhibitors. In two mouse models of gout, oral administration of PCB2 suppressed MSU crystals-induced increasing expression of IL-1β, Cathepsin B and NLRP3 in the air pouch skin and paws, accompanied with the downregulation prostaglandin E2 (PGE2) in pouch exudates. Inflammatory immune cell infiltration including macrophages and neutrophils were significantly blocked by PCB2 in air pouch skin and paws of mice gout groups. PCB2 also suppressed the release of IL-1β and Cathepsin B induced by MSU plus LPS in MPM. Our results suggest that the inhibitory effects of PCB2 on NLRP3 inflammasome may alleviate inflammatory response in gout, and this might be a promising anti-inflammatory mechanism of PCB2 against the inflammation in gout.

痛风是全球最普遍的炎性关节炎，释放了构成该疾病标志的白介素-1β（IL-1β）和组织蛋白酶B炎性介质。在本文中，我们旨在研究天然饮食化合物原花青素B2（PCB2）是否能抑制MSU晶体刺激的痛风炎症。用脂多糖（LPS）和MSU处理后，与单独用MSU或LPS处理的小鼠相比，小鼠腹膜巨噬细胞（MPM）和小鼠骨髓源性巨噬细胞（BMDM）释放了​​大量成熟的IL-1β。被TLR4及其下游效应抑制剂阻断。在两种痛风小鼠模型中，口服PCB2可抑制MSU晶体诱导的气袋皮肤和爪中IL-1β，组织蛋白酶B和NLRP3表达的增加，伴随着袋状分泌物中前列腺素E2（PGE2）的下调。痛风组小鼠气袋皮肤和足爪中的PCB2明显阻断了包括巨噬细胞和嗜中性粒细胞在内的炎性免疫细胞浸润。PCB2还抑制了MSU加LPS在MPM中诱导的IL-1β和组织蛋白酶B的释放。我们的结果表明，PCB2对NLRP3炎性体的抑制作用可能减轻痛风中的炎症反应，这可能是PCB2对痛风中炎症的有希望的抗炎机制。