Butrin, Isobutrin, and Butein from Medicinal Plant Butea monosperma Selectively Inhibit Nuclear Factor-κB in Activated Human Mast Cells: Suppression of Tumor Necrosis Factor-α, Interleukin (IL)-6, and IL-8
Butrin, Isobutrin, and Butein from Medicinal Plant Butea monosperma Selectively Inhibit Nuclear Factor-κB in Activated Human Mast Cells: Suppression of Tumor Necrosis Factor-α, Interleukin (IL)-6, and IL-8
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DOI：
10.1124/jpet.109.165209
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发表时间：
2010-05-01
影响因子：
3.5
通讯作者：
Haqqi, Tariq M.
中科院分区：
文献类型：
--
作者：
Rasheed, Zafar;Akhtar, Nahid;Haqqi, Tariq M.
类风湿性滑膜组织中肥大细胞的活化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。Butea monosperma（BM）是印度和热带地区的一种著名药用植物。本研究的目的是检查是否BM花（BME）的标准化提取物可以抑制炎症反应，在人肥大细胞（HMC）使用活化的HMC-1细胞作为模型。四个先前表征的多酚-butrin，isobutrin，isocoreopsin，和butein-从BME分离制备薄层色谱法，并通过液相色谱/质谱分析，其纯度和分子量测定。我们的研究结果表明，butrin，异butrin，和butein显着减少佛波醇12-肉豆蔻酸酯13-乙酸酯和钙离子载体A23187诱导的炎症基因的表达和生产的TNF-α，IL-6，IL-8在HMC-1细胞通过抑制NF-κ B的激活。此外，异丁酸甘油酯通过抑制I κ B α降解而在抑制NF-κ B p65活化方面是最有效的，而丁酸甘油酯和Butein的有效性相对较低。体外激酶活性测定显示异丁灵是I κ B激酶复合物活性的有效抑制剂。这是第一份报告，确定了BME及其成分butrin，isobutrin和butein的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，潜在的治疗价值，用于治疗炎症和其他疾病，其中活化的肥大细胞发挥作用。
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-kappa B. In addition, isobutrin was most potent in suppressing the NF-kappa B p65 activation by inhibiting I kappa B alpha degradation, whereas butrin and butein were relatively less effective. In vitro kinase activity assay revealed that isobutrin was a potent inhibitor of I kappa B 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.