Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, People's Republic of China.
Laboratory Animal Research Center for Science and Technology, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, People's Republic of China.
Phytother Res. 2023 Feb;37(2):731-742. doi: 10.1002/ptr.7656. Epub 2022 Oct 5.
Curcumin (Cur) is a natural active phenolic compound extracted from the root of Curcuma Longa L. It has anti-inflammatory, anti-tumor and other pharmacological activities, and is commonly used to treat ulcerative colitis (UC). However, it is not clear whether curcumin regulates the function and differentiation of Breg cells to treat UC. In this study, mice with chronic colitis were induced by dextran sulfate sodium (DSS), and treated with curcumin for 12 days. Curcumin effectively improved the body weight, colonic weight, colonic length, decreased colonic weight index and pathological injury score under colonoscopy in mice with chronic colitis, and significantly inhibited the production of IL-1β, IL-6, IL-33, CCL-2, IFN-γ, TNF-α, and promoted the secretion of IL-4, IL-10, IL-13 and IgA. Importantly, curcumin markedly upregulated CD3 CD19 CD1d , CD3 CD19 CD25 , CD3 CD19 Foxp3 Breg cells level and significantly down-regulated CD3 CD19 PD-L1 , CD3 CD19 tim-1 , CD3 CD19 CD27 Breg cells level. In addition, our results also showed that curcumin observably inhibited TLR2, TLR4, TLR5, MyD88, IRAK4, p-IRAK4, NF-κB P65, IRAK1, TRAF6, TAB1, TAB2, TAK1, MKK3, MKK6, p38MAPK, p-p38MAPK and CREB expression in TLR/MyD88 signaling pathway. These results suggest that curcumin can regulate the differentiation and function of Breg cell to alleviate DSS-induced colitis, which may be realized by inhibiting TLR/MyD88 pathway.
姜黄素（Cur）是从姜黄属植物的根部提取的一种天然活性酚类化合物。它具有抗炎、抗肿瘤等药理活性，常用于治疗溃疡性结肠炎（UC）。然而，尚不清楚姜黄素是否通过调节 Breg 细胞的功能和分化来治疗 UC。在本研究中，采用葡聚糖硫酸钠（DSS）诱导慢性结肠炎小鼠模型，并用姜黄素处理 12 天。结果显示，姜黄素能有效改善慢性结肠炎小鼠的体重、结肠重量、结肠长度，降低结肠重量指数和结肠组织学损伤评分，显著抑制白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-33（IL-33）、C 趋化因子配体 2（CCL-2）、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）的产生，促进白细胞介素-4（IL-4）、白细胞介素-10（IL-10）、白细胞介素-13（IL-13）和 IgA 的分泌。重要的是，姜黄素显著上调 CD3+CD19+CD1d+、CD3+CD19+CD25+、CD3+CD19+Foxp3+Breg 细胞水平，显著下调 CD3+CD19+PD-L1+、CD3+CD19+tim-1+、CD3+CD19+CD27+Breg 细胞水平。此外，我们的结果还表明，姜黄素明显抑制 TLR2、TLR4、TLR5、MyD88、IRAK4、p-IRAK4、核因子-κB P65（NF-κB P65）、IRAK1、TRAF6、TAB1、TAB2、TAK1、丝裂原活化蛋白激酶 3/6（MKK3/6）、p38MAPK、p-p38MAPK 和环磷酸腺苷反应元件结合蛋白（CREB）在 TLR/MyD88 信号通路中的表达。这些结果提示，姜黄素可能通过抑制 TLR/MyD88 通路来调节 Breg 细胞的分化和功能，从而缓解 DSS 诱导的结肠炎。
