Exploring the Mechanism of Indigo Naturalis in the Treatment of Ulcerative Colitis Based on TLR4/MyD88/NF-κB Signaling Pathway and Gut Microbiota.
Exploring the Mechanism of Indigo Naturalis in the Treatment of Ulcerative Colitis Based on TLR4/MyD88/NF-κB Signaling Pathway and Gut Microbiota.
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基于TLR4/MyD88/NF-kappa B信号通路与肠道菌群探讨青黛治疗溃疡性结肠炎的机制
DOI：
10.3389/fphar.2021.674416
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发表时间：
2021
影响因子：
5.6
通讯作者：
Xie CG
中科院分区：
文献类型：
--
作者：
Yang QY;Ma LL;Zhang C;Lin JZ;Han L;He YN;Xie CG
背景：临床试验证明，青黛是治疗溃疡性结肠炎的候选药物，但其作用机制尚不清楚。目的：探讨青黛对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎的保护作用及其机制。方法：给DSS诱导的UC小鼠灌胃青黛(200 mg/kg)、青黛(4.76 mg/kg)和靛玉红(0.78 mg/kg)治疗1周。采用病理切片、炎症因子、免疫印迹和16S rRNA测序等方法研究了青黛的抗UC作用机制。结果：从体重变化、疾病活动指数和结肠长度来看，青黛的抗DSS所致UC作用最强，其次是青黛和青黛。病理切片显示，青黛、青黛、靛玉红均能减少炎性细胞的浸润，增加肠粘液的分泌，修复肠粘膜。青黛、青黛、靛玉红可通过抑制TLR4/MYD88/NF-βB信号转导途径，降低IL-1α、IL-6和肿瘤坏死因子-κ。青黛和青黛还能降低血清和结肠组织中的IgA和Ig G。此外，天然青黛、青黛和靛玉红还可以调整DSS诱导的UC小鼠肠道微生物区系结构，降低肠道菌群/类杆菌的比例，增加益生菌的丰度。结论：青黛和靛玉红是青黛抗UC的主要成分之一。INN能调节肠道菌群，减轻炎症反应，修复肠粘膜，改善UC小鼠的生理状态，其抗UC机制可能与抑制TLR4/MyD88/NF-κB信号转导有关。
Background: Clinical trials have proven that indigo naturalis is a candidate drug for treating ulcerative colitis (UC), but its therapeutic mechanism is still unclear. Purpose: This study aimed to evaluate the protective effect and mechanism of indigo naturalis to treat mice with dextran sulfate sodium (DSS)-induced UC. Methods: DSS-induced UC mice were treated with indigo naturalis (200 mg/kg), indigo (4.76 mg/kg), and indirubin (0.78 mg/kg) for 1 week. The anti-UC mechanism of indigo naturalis was studied by pathological section, inflammatory factor, western blot, and 16S rRNA sequencing. Results: According to body weight change, disease activity index, and colon length, indigo naturalis had the strongest anti DSS-induced UC effect, followed by indirubin and indigo. Pathological section showed that indigo naturalis, indigo, and indirubin could reduce the infiltration of inflammatory cells, increase the secretion of intestinal mucus, and repair the intestinal mucosa. Indigo naturalis, indigo, and indirubin could reduce IL-1β,IL-6, and TNF-α by inhibiting TLR4/MyD88/NF-κB signal transduction. Indigo naturalis and indigo could also reduce IgA and IgG both in serum and colon tissue. In addition, indigo naturalis, indigo, and indirubin could adjust the gut microbiota structure of DSS-induced UC mice, reducing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of probiotics. Conclusion: Indigo and indirubin are one of the main anti-UC components of indigo naturalis. INN could regulate intestinal flora, reduce inflammation, repair intestinal mucosa, and improve the physiological status of DSS-induced UC mice and its anti-UC mechanism may be involved in inhibiting TLR4/MyD88/NF-κB signal transduction.
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影响因子：
2.4
作者：
Saito R;Tamura M;Matsui H;Nagano Y;Suzuki H;Kaneko T;Mizokami Y;Hyodo I
通讯作者：
Hyodo I
影响因子：
--
作者：
Azad MAK;Sarker M;Wan D
通讯作者：
Wan D
影响因子：
8
作者：
Harbord, Marcus;Eliakim, Rami;Carbonnel, Franck
通讯作者：
Carbonnel, Franck
影响因子：
2.5
作者：
Gao, Wenyan;Guo, Yufang;Gong, Yang
通讯作者：
Gong, Yang
影响因子：
1.2
作者：
Urushikubo, Jun;Yanai, Shunichi;Matsumoto, Takayuki
通讯作者：
Matsumoto, Takayuki