Liu Miaohua, Liu Fuchun, Pan Yuanle, Xiong Yi, Zeng Xin, Zheng LinXin, Zhao Haimei, Li Yanzhen, Liu Duanyong
Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
College of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
Int Immunopharmacol. 2023 Feb;115:109612. doi: 10.1016/j.intimp.2022.109612. Epub 2022 Dec 28.
It is common knowledge that the crosstalk of gut microbiota (GM) and dendritic cells (DCs) are critical for the pathogenesis of inflammatory bowel disease (IBD). As a major bioactive constituent derived from the root of the Sophora flavescens, Oxymatrine (OMT) was used to treat IBD in China. However, it is still unknown whether OMT ameliorates IBD by regulating the crosstalk between DCs and GM. In the present study, after 10 days of OMT (100 mg/kg/day) treated mice with colitis induced by dextran sulfate sodium (DSS), the change rate of body weight, colon weight, colon weight index, colon length, DAI score and colonic pathological damage scores of colitis mice were significantly ameliorate, followed with fewer ulceration and inflammatory cell infiltration, the increased expression of IL-4 and IL-13, and the decreased expression of CCL-2, IL-33 and IFN-γ. The percents of inflammatory DCs (such as TNF-αDCs, iNOSDCs, CXCR5DCs and E-cadherinDCs) were markedly decreased, and the GM composition was regulated. Importantly, it is positive correlated between the efficacy of OMT on colitis, GM and inflammatory DCs. Meanwhile, Western blotting assay showed that OMT suppressed the activation of TLR4, Myd88, IRAK4, IRAK1, TRAF6, TAK1, TAB, MKK3, MKK6, P38, NF-κB in the TLR / NF-κB signaling pathway. In summary, OMT exhibits the protective effect against the DSS-induced experimental colitis, which was achieved by regulating the crosstalk of inflammatory DCs and GM, and inhibiting the TLR / NF-κB signaling pathway.
众所周知，肠道微生物群（GM）与树突状细胞（DCs）之间的相互作用对炎症性肠病（IBD）的发病机制至关重要。氧化苦参碱（OMT）作为苦参根中的一种主要生物活性成分，在中国被用于治疗IBD。然而，OMT是否通过调节DCs与GM之间的相互作用来改善IBD仍不清楚。在本研究中，用硫酸葡聚糖钠（DSS）诱导小鼠发生结肠炎，给予OMT（100mg/kg/天）处理10天后，结肠炎小鼠的体重变化率、结肠重量、结肠重量指数、结肠长度、疾病活动指数（DAI）评分和结肠病理损伤评分均得到显著改善，溃疡和炎性细胞浸润减少，白细胞介素-4（IL-4）和白细胞介素-13表达增加，趋化因子配体-2（CCL-2）、白细胞介素-33（IL-33）和干扰素-γ（IFN-γ）表达降低。炎性DCs（如肿瘤坏死因子-αDCs、诱导型一氧化氮合酶DCs、CXC趋化因子受体5DCs和E-钙黏蛋白DCs）的比例显著降低，GM组成得到调节。重要的是，OMT对结肠炎的疗效与GM和炎性DCs呈正相关。同时，蛋白质免疫印迹分析表明，OMT抑制了Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路中TLR4、髓样分化因子88（Myd88）、白细胞介素-1受体相关激酶4（IRAK4）、白细胞介素-1受体相关激酶1（IRAK1）、肿瘤坏死因子受体相关因子6（TRAF6）、转化生长因子β激活激酶1（TAK1）、TAK1结合蛋白（TAB）、丝裂原活化蛋白激酶激酶3（MKK3）、丝裂原活化蛋白激酶激酶6（MKK6）、p38丝裂原活化蛋白激酶（P38）、NF-κB的激活。综上所述，OMT对DSS诱导的实验性结肠炎具有保护作用，其机制是通过调节炎性DCs与GM之间的相互作用，并抑制TLR/NF-κB信号通路实现的。
