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鸦胆子油乳剂对实验性大鼠克罗恩病的治疗作用:涉及 TLR4/NF-κB 信号通路。

Therapeutic effect of Brucea javanica oil emulsion on experimental Crohn's disease in rats: Involvement of TLR4/ NF-κB signaling pathway.

机构信息

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China; School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China.

出版信息

Biomed Pharmacother. 2019 Jun;114:108766. doi: 10.1016/j.biopha.2019.108766. Epub 2019 Mar 20.

Abstract

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.

摘要

鸦胆子油乳剂对大鼠 2,4,6-三硝基苯磺酸诱导的克罗恩病的治疗作用及机制研究

鸦胆子是一种传统的中国民间药物,常用于治疗痢疾(也称为炎症性肠病)。鸦胆子油乳剂(BJOE)是鸦胆子最常见的制剂,具有多种药理活性。在本后续研究中,我们致力于阐明 BJOE 对大鼠 2,4,6-三硝基苯磺酸(TNBS)诱导的克罗恩病(CD)的潜在益处,并阐明其作用机制。结果表明,BJOE 治疗可显著减轻体重减轻、疾病活动指数和宏观评分,改善结肠缩短,阻止结肠组织病理学恶化,平行于模型组降低组织学评分。此外,BJOE 还降低了 MPO 和促炎细胞因子(TNF-α、IL-1β、IL-6、IL-17、IL-23 和 IFN-γ)的水平,并增加了抗炎细胞因子(IL-4、IL-10 和 TGF-β)的水平,与模型组相比。此外,BJOE、SASP 或 AZA 治疗可显著抑制 TNBS 诱导的 MMP-1、MMP-3 和 RAGE 的 mRNA 表达,而 PPAR-γ 的 mRNA 表达显著增强。此外,与 TNBS 处理的大鼠相比,AZA 和 BJOE 治疗可显著抑制 TLR4/NF-κB 信号通路的激活。我们的研究表明,BJOE 在治疗大鼠 TNBS 诱导的结肠炎方面优于 SASP 和 AZA。BJOE 的保护作用可能涉及抑制 TLR4/NF-κB 介导的炎症反应。这些结果表明,BJOE 具有很大的潜力进一步开发为治疗 CD 的新型候选药物。

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