Ginsenoside Rh2 alleviates ulcerative colitis by regulating the STAT3/miR-214 signaling pathway
Ginsenoside Rh2 alleviates ulcerative colitis by regulating the STAT3/miR-214 signaling pathway
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人参皂苷Rh2通过调节STAT3/miR-214信号通路缓解溃疡性结肠炎
DOI：
10.1016/j.jep.2021.113997
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发表时间：
2021-03-24
影响因子：
5.4
通讯作者：
Liu, Shijia
中科院分区：
文献类型：
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作者：
Chen, Xuanqing;Xu, Tingting;Liu, Shijia
民族药理意义：人参是中国用于预防和治疗癌症、糖尿病、心血管疾病等疾病的珍贵中草药。人参皂苷作为人参的主要活性成分，具有广泛的药理作用。人参皂苷Rh2是从人参中提取的一种原人参二醇皂苷，具有抗炎、抗癌等作用。研究目的：Rh2治疗溃疡性结肠炎(UC)的潜在生物学机制尚不清楚。本研究旨在探讨Rh2对葡聚糖硫酸钠(DSS)诱导的结肠炎的治疗作用，并阐明Rh2治疗UC的作用机制。方法：建立DSS诱导的UC小鼠模型，随机分为4组：对照组、DSS组、Rh2(50 mg/kg)组和柳氮磺吡啶(SASP，200 mg/kg)组。除对照组外，各组均给予3%DSS饮水，连续7d，其余两组分别给予Rh2和SASP灌胃10d。实验结束后，采集结肠标本，对UC小鼠进行表型和病理分析。用Western印迹、免疫组织化学和实时定量聚合酶链式反应检测信号通路相关因子的表达。结果：RH2能显著减轻DSS诱导的体重减轻、肠道损伤、结肠长度缩短和疾病活动指数(DAI)评分。此外，Rh2还可降低促炎细胞因子，如肿瘤坏死因子-α、白介素6和白介素1-α。此外，Rh2对STAT3/miR-214的激活也有抑制作用。在体外，我们发现Rh2有效地抑制了IL-6诱导的正常结肠上皮细胞STAT3的磷酸化和miR-214的表达。结论：Rh2在UC的治疗中具有潜在的应用价值，其作用机制与下调STAT3/miR-214水平有关，有望用于临床UC的治疗。
Ethnopharmacological relevance: Ginseng is a valuable medicinal herb used in China for the prevention and treatment of cancer, diabetes, cardiovascular diseases and other diseases. As the main active ingredient of ginseng, ginsenoside has a wide range of pharmacological effects. Ginsenoside Rh2, a protopanaxadiol saponin from ginseng, exhibits anti-inflammatory and anticancer effects. Aim of the study: The potential biological mechanism of Rh2 in the treatment of ulcerative colitis (UC) has not been clarified clearly. In our research, we aimed to explore the therapeutic effects of Rh2 on dextran sodium sulfate (DSS)-induced colitis and elucidate the mechanism of Rh2 in treating UC. Methods: DSS-induced UC mice were established and randomly divided into the following four groups: control group, DSS group, Rh2 (50 mg/kg) group and sulfasalazine (SASP, 200 mg/kg) group. Except for the control group, 3% DSS drinking water was given to each group for 7 days, and the other two groups were intragastrically administered with Rh2 and SASP for 10 days. At the end of the experiment, colon samples were collected, and phenotypic and pathological analyses were performed in UC mice. Then, Western blot, immunohistochemistry and quantitative real-time PCR analyses were performed to determine the expression of signaling pathwayrelated factors. Results: Rh2 markedly alleviated DSS-induced body weight loss, intestinal damage, colon length shortening and disease activity index (DAI) scores. Furthermore, proinflammatory cytokines, such as TNF-?, IL-6 and IL-1?, were reduced by Rh2. Additionally, STAT3/miR-214 activation was also suppressed by Rh2 administration. In vitro, we demonstrated that Rh2 effectively inhibited IL-6-induced STAT3 phosphorylation and miR-214 expression in cultured normal colonic epithelial cells. Conclusion: Our results suggested that Rh2 exhibits potential application value in the treatment of UC, and its mechanism is related to the downregulation of STAT3/miR-214 levels, which is expected to be applicable in the treatment of clinical UC.