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紫云英苷B4通过抑制TLR4/NF-κB/MAPK信号通路预防急性溃疡性结肠炎。

Anemoside B4 prevents acute ulcerative colitis through inhibiting of TLR4/NF-κB/MAPK signaling pathway.

作者信息

Ma Huimiao, Zhou Mengjing, Duan Wenbin, Chen Lanying, Wang Lingling, Liu Peng

机构信息

School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China; National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.

National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.

出版信息

Int Immunopharmacol. 2020 Oct;87:106794. doi: 10.1016/j.intimp.2020.106794. Epub 2020 Jul 17.

Abstract

Anemoside B4 (B4) is a compound extracted from Pulsatilla chinensis(P. chinensis). Pharmacological studies have proved that it has certain anti-inflammatory activity. Acute ulcerative colitis (ulcerative colitis) is a non-specific inflammatory disease whose pathogenesis is not completely known, and there is no effective drugs. The purpose of this study was to investigate the protective effect of B4 on ulcerative colitis and its mechanism. In this study, the C57BL/6 mice model of ulcerative colitis was established by DSS [3% (w/v)] and treated with intraperitoneal injection of B4 and oral administration of mesalazine, respectively. During the experiment, the clinical symptoms of the mice were scored by the disease activity index (DAI). Histopathological changes were observed by HE staining. In addition, the effect of LPS on Raw264.7 cells was also studied. In vivo studies showed that B4 could prevent DSS-induced colitis mice from losing weight, shortening colon length and improving pathological changes of colon tissues. B4 significantly reduced levels of inflammatory cytokines IL-1β, IL-6, and TNF-α in colon tissues. In vitro experiments, B4 was almost nontoxic to Raw264.7 cells and could protect the Raw264.7 cells induced by LPS. In terms of mechanism, B4 significantly inhibited the activation of the TLR4 signaling pathway induced by DSS and down-regulate the expression of key proteins in the TLR4/NF-κB/MAPK signaling pathway in Raw264.7 cells induced by LPS. These findings suggest that the inhibition of B4 on ulcerative colitis may be through the TLR4/NF-κB/MAPK pathway. Therefore, B4 may be used as a potential drug for the treatment of ulcerative colitis.

摘要

白头翁皂苷B4(B4)是从白头翁中提取的一种化合物。药理研究证明其具有一定的抗炎活性。急性溃疡性结肠炎是一种发病机制尚未完全明确的非特异性炎症性疾病,且尚无有效药物。本研究旨在探讨B4对溃疡性结肠炎的保护作用及其机制。在本研究中,通过3%(w/v)的葡聚糖硫酸钠(DSS)建立C57BL/6小鼠溃疡性结肠炎模型,并分别腹腔注射B4和口服美沙拉嗪进行治疗。实验过程中,通过疾病活动指数(DAI)对小鼠的临床症状进行评分。采用苏木精-伊红(HE)染色观察组织病理学变化。此外,还研究了脂多糖(LPS)对Raw264.7细胞的影响。体内研究表明,B4可预防DSS诱导的结肠炎小鼠体重减轻、结肠长度缩短,并改善结肠组织的病理变化。B4显著降低了结肠组织中炎性细胞因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平。体外实验中,B对Raw264.7细胞几乎无毒,并可保护其免受LPS诱导。机制方面,B4显著抑制DSS诱导的Toll样受体4(TLR4)信号通路的激活,并下调LPS诱导的Raw264.7细胞中TLR4/核因子κB(NF-κB)/丝裂原活化蛋白激酶(MAPK)信号通路关键蛋白的表达。这些研究结果表明,B4对溃疡性结肠炎的抑制作用可能是通过TLR4/NF-κB/MAPK途径实现的。因此,B4可能作为治疗溃疡性结肠炎的潜在药物。

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