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人参皂苷 Rh2 通过调控 STAT3/miR-214 信号通路缓解溃疡性结肠炎。

Ginsenoside Rh2 alleviates ulcerative colitis by regulating the STAT3/miR-214 signaling pathway.

机构信息

The Affiliated Hospital of Nanjing University of Chinese Medicine, #155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu, 210029, China; School of Life Science & Technology, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.

School of Medicine & Holistic Integrative Medicine, Nan-jing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China.

出版信息

J Ethnopharmacol. 2021 Jun 28;274:113997. doi: 10.1016/j.jep.2021.113997. Epub 2021 Mar 8.

Abstract

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 pathway-related 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-α, IL-6 and IL-1β, 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.

摘要

民族药理学相关性

人参是一种在中国被广泛用于预防和治疗癌症、糖尿病、心血管疾病等疾病的有价值的药用草本植物。作为人参的主要活性成分,人参皂苷具有广泛的药理作用。人参二醇组皂苷 Rh2 是一种来自人参的原人参二醇皂苷,具有抗炎和抗癌作用。

研究目的

Rh2 治疗溃疡性结肠炎(UC)的潜在生物学机制尚未得到明确阐明。在我们的研究中,我们旨在探讨 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 的机制。

方法

建立 DSS 诱导的 UC 小鼠模型,并将其随机分为以下四组:对照组、DSS 组、Rh2(50mg/kg)组和柳氮磺胺吡啶(SASP,200mg/kg)组。除对照组外,各组给予 3% DSS 饮用水 7 天,另两组给予 Rh2 和 SASP 灌胃 10 天。实验结束时,收集结肠样本,对 UC 小鼠进行表型和病理分析。然后,通过 Western blot、免疫组化和实时定量 PCR 分析测定信号通路相关因子的表达。

结果

Rh2 显著缓解 DSS 诱导的体重减轻、肠道损伤、结肠缩短和疾病活动指数(DAI)评分。此外,Rh2 降低了促炎细胞因子 TNF-α、IL-6 和 IL-1β的表达。此外,STAT3/miR-214 的激活也被 Rh2 抑制。体外实验表明,Rh2 有效抑制了培养的正常结肠上皮细胞中 IL-6 诱导的 STAT3 磷酸化和 miR-214 的表达。

结论

我们的研究结果表明,Rh2 在治疗 UC 方面具有潜在的应用价值,其机制与下调 STAT3/miR-214 水平有关,有望应用于临床 UC 的治疗。

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