Department of Gastroenterology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Digestive System Diseases, Wuhan, P.R. China.
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, P.R. China.
Pharm Biol. 2021 Dec;59(1):974-985. doi: 10.1080/13880209.2021.1948066.
Eriodictyol (EDT) is a flavonoid with strong anti-inflammatory, anti-apoptotic, and antioxidant properties.
To investigate the protective effect and mechanism of EDT in ulcerative colitis (UC).
UC model was induced by 3% dextran sulphate sodium (DSS) solution for 7 days, meanwhile, EDT and Smoothened (Smo) inhibitor cyclopamine (Cyc) were intraperitoneally injected. In the first experiment, C57BL/6 mice divided into blank control, DSS, DSS + EDT (20 or 40 mg/kg) groups. In second experiment, added Cyc (5 mg/kg) and EDT + Cyc groups. All mice were sacrificed on day 8. Disease activity index (DAI), colon length and colon histology as well as MDA levels, SOD, and GSH-Px activities were measured. The expression of Sonic hedgehog (Shh), Patched, Smo, glioblastoma-1, zonula occludens-1 (ZO-1), occludin, cleaved caspase 3, Bax and Bcl-2 in colon was detected using RT-PCR and Western blotting.
After EDT treatment, compared with the DSS group, DAI (2.33 ± 0.516 vs. 3.67 ± 0.516), colon shortening (5.27 ± 0.476 vs. 4.53 ± 0.528 cm) and histological score (6.67 ± 1.211 vs. 12 ± 1.265) was significantly decreased. EDT also reduced inflammation, oxidative stress and apoptosis in colon. Additionally, EDT increased the expression of the tight junction proteins ZO-1 (35%) and occludin (66.3%). Mechanistically, EDT upregulated the Shh signalling pathway. However, Cyc-mediated inhibition of the Shh pathway partially abolished the effects of EDT.
These results indicate EDT attenuates DSS-induced colitis by activating the Shh pathway. Further clinical trials are needed to demonstrate its efficacy on UC.
桔皮素（EDT）是一种具有很强抗炎、抗凋亡和抗氧化特性的类黄酮。
研究 EDT 在溃疡性结肠炎（UC）中的保护作用及其机制。
通过 3%葡聚糖硫酸钠（DSS）溶液诱导 UC 模型 7 天，同时腹腔内注射 EDT 和 Smoothened（Smo）抑制剂环巴胺（Cyc）。在第一个实验中，将 C57BL/6 小鼠分为空白对照组、DSS 组、DSS+EDT（20 或 40mg/kg）组。在第二个实验中，加入 Cyc（5mg/kg）和 EDT+Cyc 组。所有小鼠于第 8 天处死。测量疾病活动指数（DAI）、结肠长度和结肠组织学以及 MDA 水平、SOD 和 GSH-Px 活性。使用 RT-PCR 和 Western blot 检测结肠中 Sonic hedgehog（Shh）、Patched、Smo、胶质细胞瘤-1、闭锁小带蛋白-1（ZO-1）、occludin、cleaved caspase 3、Bax 和 Bcl-2 的表达。
与 DSS 组相比，EDT 治疗后 DAI（2.33±0.516 与 3.67±0.516）、结肠缩短（5.27±0.476 与 4.53±0.528cm）和组织学评分（6.67±1.211 与 12±1.265）明显降低。EDT 还减轻了结肠的炎症、氧化应激和细胞凋亡。此外，EDT 增加了紧密连接蛋白 ZO-1（35%）和 occludin（66.3%）的表达。机制上，EDT 上调了 Shh 信号通路。然而，Cyc 介导的 Shh 通路抑制部分消除了 EDT 的作用。
这些结果表明，EDT 通过激活 Shh 通路减轻 DSS 诱导的结肠炎。需要进一步的临床试验来证明其在 UC 中的疗效。
