Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis.
Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis.
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DOI：
10.1038/srep28370
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发表时间：
2016-06-20
影响因子：
4.6
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
He X;Wei Z;Wang J;Kou J;Liu W;Fu Y;Yang Z
草豆蔻素是草豆蔻中的一种有效成分，具有抗菌、抗肿瘤等重要的生物活性。然而，山姜素对炎症性肠病（IBD）的影响尚未报道。本研究旨在探讨山姜素对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的抗炎作用及其机制。在体内，通过给小鼠饮用含有5%（w/v）DSS的水7天来建立DSS诱导的小鼠结肠炎模型。在DSS处理前3天，通过腹膜内注射每天一次给予Alpinetin（25、50和100 mg/kg）。在体外，佛波酯肉豆蔻酸酯（PMA）分化的单核细胞THP-1巨噬细胞用山姜素处理和脂多糖（LPS）刺激。结果表明，山姜素能明显减轻小鼠腹泻、结肠缩短、组织学损伤、髓过氧化物酶（MPO）活性、肿瘤坏死因子（TNF-α）和白细胞介素（IL-1β）的表达。在体外实验中，alpinetin显著抑制LPS诱导的TNF-α和IL-1β的产生，以及Toll样受体4（TLR 4）介导的核转录因子-κ B（NF-κB）和NOD样受体蛋白3（NLRP 3）炎性小体的激活。总之，本研究表明，山姜素对DSS诱导的结肠炎具有保护作用，可能是一种有前途的结肠炎治疗剂。
Alpinetin, a composition of Alpinia katsumadai Hayata, has been reported to have a number of biological properties, such as antibacterial, antitumor and other important therapeutic activities. However, the effect of alpinetin on inflammatory bowel disease (IBD) has not yet been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of alpinetin on dextran sulfate sodium (DSS)-induced colitis in mice. In vivo, DSS-induced mice colitis model was established by giving mice drinking water containing 5% (w/v) DSS for 7 days. Alpinetin (25, 50 and 100 mg/kg) were administered once a day by intraperitoneal injection 3 days before DSS treatment. In vitro, phorbol myristate acetate (PMA)-differentiated monocytic THP-1 macrophages were treated with alpinetin and stimulated by lipopolysaccharide (LPS). The results showed that alpinetin significantly attenuated diarrhea, colonic shortening, histological injury, myeloperoxidase (MPO) activity and the expressions of tumor necrosis factor (TNF-α) and interleukin (IL-1β) production in mice. In vitro, alpinetin markedly inhibited LPS-induced TNF-α and IL-1β production, as well as Toll-like receptor 4 (TLR4) mediated nuclear transcription factor-kappaB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, this study demonstrated that alpinetin had protective effects on DSS-induced colitis and may be a promising therapeutic reagent for colitis treatment.