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从药用植物 Butea monosperma 中分离得到的布他醇、异布他醇和布替醇选择性抑制活化的人肥大细胞中的核因子-κB:抑制肿瘤坏死因子-α、白细胞介素 (IL)-6 和 IL-8。

Butrin, isobutrin, and butein from medicinal plant Butea monosperma selectively inhibit nuclear factor-kappaB in activated human mast cells: suppression of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8.

机构信息

Department of Pathology, Microbiology, and Immunology, University of South Carolina, Columbia, South Carolina, USA.

出版信息

J Pharmacol Exp Ther. 2010 May;333(2):354-63. doi: 10.1124/jpet.109.165209. Epub 2010 Feb 17.

Abstract

Activation of mast cells in rheumatoid synovial tissue has often been associated with tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 production and disease pathogenesis by adjacent cell types. Butea monosperma (BM) is a well known medicinal plant in India and the tropics. The aim of this study was to examine whether a standardized extract of BM flower (BME) could inhibit inflammatory reactions in human mast cells (HMC) using activated HMC-1 cells as a model. Four previously characterized polyphenols--butrin, isobutrin, isocoreopsin, and butein--were isolated from BME by preparative thin layer chromatography, and their purity and molecular weights were determined by liquid chromatography/mass spectrometry analysis. Our results showed that butrin, isobutrin, and butein significantly reduced the phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced inflammatory gene expression and production of TNF-alpha, IL-6, and IL-8 in HMC-1 cells by inhibiting the activation of NF-kappaB. In addition, isobutrin was most potent in suppressing the NF-kappaB p65 activation by inhibiting IkappaBalpha degradation, whereas butrin and butein were relatively less effective. In vitro kinase activity assay revealed that isobutrin was a potent inhibitor of IkappaB kinase complex activity. This is the first report identifying the molecular basis of the reported anti-inflammatory effects of BME and its constituents butrin, isobutrin, and butein. The novel pharmacological actions of these polyphenolic compounds indicate potential therapeutic value for the treatment of inflammatory and other diseases in which activated mast cells play a role.

摘要

滑膜组织中肥大细胞的激活通常与肿瘤坏死因子 (TNF)-α、白细胞介素 (IL)-6 和 IL-8 的产生以及相邻细胞类型的疾病发病机制有关。蒲桃是印度和热带地区一种著名的药用植物。本研究旨在探讨蒲桃花(BME)的标准化提取物是否可以通过激活的 HMC-1 细胞作为模型来抑制人肥大细胞(HMC)中的炎症反应。通过制备性薄层色谱法从 BME 中分离出四种先前表征的多酚-布廷、异布廷、异考沙辛和布替宁,并通过液相色谱/质谱分析确定其纯度和分子量。我们的结果表明,布廷、异布廷和布替宁通过抑制 NF-κB 的激活,显著降低了佛波醇 12-肉豆蔻酸 13-乙酸酯和钙离子载体 A23187 诱导的 HMC-1 细胞中炎症基因的表达和 TNF-α、IL-6 和 IL-8 的产生。此外,异布廷通过抑制 IkappaBalpha 的降解,在抑制 NF-κB p65 激活方面最为有效,而布廷和布替宁则相对较弱。体外激酶活性测定表明,异布廷是一种有效的 IkappaB 激酶复合物活性抑制剂。这是首次报道鉴定 BME 及其成分布廷、异布廷和布替宁抗炎作用的分子基础。这些多酚化合物的新的药理作用表明,它们在治疗肥大细胞激活相关的炎症和其他疾病方面具有潜在的治疗价值。

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