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通过抑制 STAT3/NF-кB 通路介导的炎症反应,环烯醚萜苷对急性结肠炎具有保护作用。

Protective effects of iridoid glycosides on acute colitis via inhibition of the inflammatory response mediated by the STAT3/NF-кB pathway.

机构信息

Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China.

Department of Basic Medical Sciences, School of Medicine, Xiamen University, Xiamen 361102, China.

出版信息

Int Immunopharmacol. 2020 Apr;81:106240. doi: 10.1016/j.intimp.2020.106240. Epub 2020 Feb 7.

Abstract

Morroniside and loganin are iridoid glycosides extracted from Cornus officinalis, a plant species widely used in traditional Chinese medicine. However, the anti-inflammatory effects of morroniside and loganin in colitis are barely understood. The aim of the present study was to explore the effects of morroniside and loganin on the dextran sodium sulfate (DSS)-induced murine model of colitis and an LPS-induced colorectal cancer (CRC) cell inflammation model, and to clarify the underlying mechanisms. We found that morroniside and loganin were able to ameliorate clinical features, including disease activity index (DAI), histological inflammation score and periodic acid-Schiff staining (PAS). In the mouse model, morroniside and loganin treatment increased expression of tight junction proteins (TJs) and decreased pro-inflammatory cytokine production. Moreover, our findings showed that the expression of p-STAT3 and p-p65 were suppressed compared to the disease group. In in vitro experiments, treatment with morroniside and loganin had no obvious effects on proliferative activity in HCT116 cells and HIEC-6 cells. Expression of pro-inflammatory cytokines was inhibited by morroniside and loganin treatment in comparison with the LPS-treated group. Taken together, morroniside and loganin have beneficial effects on colitis in vivo and are anti-inflammatory in vitro. Possible mechanisms of the anti-inflammatory response may include blockade of the STAT3/NF-κB pathway.

摘要

莫诺苷和马钱苷是从山茱萸中提取的环烯醚萜苷,山茱萸是一种广泛应用于中药的植物。然而,莫诺苷和马钱苷对结肠炎的抗炎作用知之甚少。本研究旨在探讨莫诺苷和马钱苷对葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎模型和脂多糖(LPS)诱导的结直肠癌细胞炎症模型的影响,并阐明其潜在机制。我们发现,莫诺苷和马钱苷能够改善临床特征,包括疾病活动指数(DAI)、组织学炎症评分和过碘酸希夫染色(PAS)。在小鼠模型中,莫诺苷和马钱苷治疗增加了紧密连接蛋白(TJs)的表达,减少了促炎细胞因子的产生。此外,与疾病组相比,我们的研究结果表明 p-STAT3 和 p-p65 的表达受到抑制。在体外实验中,莫诺苷和马钱苷处理对 HCT116 细胞和 HIEC-6 细胞的增殖活性没有明显影响。与 LPS 处理组相比,莫诺苷和马钱苷处理抑制了促炎细胞因子的表达。总之,莫诺苷和马钱苷对体内结肠炎有有益的作用,并且在体外具有抗炎作用。抗炎反应的可能机制包括阻断 STAT3/NF-κB 通路。

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