Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-κB signaling and T-helper cell homeostasis
Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-κB signaling and T-helper cell homeostasis
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DOI：
10.1007/s00011-016-1005-3
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发表时间：
2017-02-01
影响因子：
6.7
通讯作者：
Zhang, Yu-Bin
中科院分区：
文献类型：
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作者：
Chen, Ying-Ying;Li, Rui-Yan;Zhang, Yu-Bin
据报道，NF-κ B 信号传导的激活和辅助性 T (Th) 细胞的失衡在结肠炎的发病机制中发挥着关键作用。黄柏（CPC）通常用于治疗炎症和腹泻。在我们之前的研究中，据报道，CPC 的一种成分去亚甲基小檗碱 (DMB) 作为一种新型天然线粒体靶向抗氧化剂可以治疗酒精性肝病。在本研究中，我们探讨了DMB是否可以通过调节NF-κB通路和Th细胞稳态来预防葡聚糖硫酸钠（DSS）诱导的小鼠炎症性结肠炎。用3% DSS诱导炎症性结肠炎小鼠，并按150和300 mg/kg的剂量口服DMB。体外，在脂多糖（LPS）刺激前将DMB（10、20、40μM）和N-乙酰半胱氨酸（NAC，5mM）与RAW264.7共培养2小时，离体培养小鼠脾细胞48小时进行免疫反应测试。在体内，DMB显着减轻体重减轻并减少 髓过氧化物酶（MPO）活性，同时显着降低促炎细胞因子的产生，如白细胞介素（IL）-6和肿瘤坏死因子-α（TNF-α），并抑制NF-κB信号通路的激活。此外，DMB 降低了干扰素 (IFN)-gamma，增加了小鼠脾细胞中 IL-4 的浓度以及血清中 IgG1/IgG2a 的比率。在体外，DMB 显着抑制 RAW264.7 细胞中 ROS 的产生和促炎细胞因子。我们的研究结果表明，DMB 通过抑制 NF-kappa B 通路和调节 Th 细胞的平衡来减轻小鼠结肠炎并抑制炎症反应。
The activation of NF-kappa B signaling and unbalance of T-helper (Th) cells have been reported to play a key role in the pathogenesis of colitis. Cortex Phellodendri Chinensis (CPC) is commonly used to treat inflammation and diarrhea. Demethyleneberberine (DMB), a component of CPC, was reported to treat alcoholic liver disease as a novel natural mitochondria-targeted antioxidant in our previous study. In this study, we investigated whether DMB could protect against dextran sulfate sodium (DSS)-induced inflammatory colitis in mice by regulation of NF-kappa B pathway and Th cells homeostatis.Inflammatory colitis mice were induced by 3% DSS, and DMB were orally administered on the doses of 150 and 300 mg/kg. In vitro, DMB (10, 20, 40 mu M) and N-acetyl cysteine (NAC, 5 mM) were co-cultured with RAW264.7 for 2 h prior to lipopolysaccharide (LPS) stimulation, and splenocytes from the mice were cultured ex vivo for 48 h for immune response test.In vivo, DMB significantly alleviated the weight loss and diminished myeloperoxidase (MPO) activity, while significantly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha), and inhibited the activation of NF-kappa B signaling pathway. Furthermore, DMB decreased interferon (IFN)-gamma, increased IL-4 concentration in the mice splenocytes and the ratio of IgG1/IgG2a in the serum. In vitro, ROS production and pro-inflammation cytokines were markedly inhibited by DMB in RAW264.7 cell.Our findings revealed that DMB alleviated mice colitis and inhibited the inflammatory responses by inhibiting NF-kappa B pathway and regulating the balance of Th cells.