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首页> 外文期刊>Journal of Translational Medicine >Differential immunomodulatory effects by Tripterygium wilfordii Hook f-derived refined extract PG27 and its purified component PG490 (triptolide) in human peripheral blood T cells: potential therapeutics for arthritis and possible mechanisms explaining in part Chinese herbal theory “Junn-Chenn-Zuou-SS”
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Differential immunomodulatory effects by Tripterygium wilfordii Hook f-derived refined extract PG27 and its purified component PG490 (triptolide) in human peripheral blood T cells: potential therapeutics for arthritis and possible mechanisms explaining in part Chinese herbal theory “Junn-Chenn-Zuou-SS”

机译：雷公藤的提取物PG27及其纯化成分PG490（雷公藤内酯醇）在人外周血T细胞中的差异免疫调节作用：关节炎的潜在疗法和可能的机制，部分解释了中草药理论“ Junn-Chenn-Zuou-SS”

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Background For thousands of years, it remains unclear why Chinese prefer complex herbal remedy and seldom try to purify it. One of the reasons is that they believe Chinese herbs compared to Western drugs are relatively less toxic and better tolerated. The so called “Junn-Chenn-Zuou-SS” theory illustrates a concept of coordinated effects from a combination of different Chinese herbs. PG27, a refined extract from a well-known Chinese antirheumatic herb Tripterygium wilfordii Hook f (TwHf), is effective in attenuating transplantation rejection and extending survival of cardiac xenografts. Methods Experiments were conducted in human primary T lymphocytes isolated from buffy coat. The activities of the inhibitor of kappaB alpha kinase-inhibitor of kappaB alpha-nuclear factor kappaB (IKK-IκBα-NF-κB) and mitogen activated protein kinase-activator protein-1 (MAPK-AP-1) signaling pathways were determined via electrophoretic mobility shift assays, immunoprecipitation kinase assays, Western blots, and transfection assays. Results We showed that PG27 inhibited IKKα-IκBα-NF-κB and MAPK-AP-1 signaling pathways; however, IKKβ activity was less susceptible to inhibition by PG27. In contrast, the purified component of TwHf, PG490 (triptolide), reduced both MAPK-AP-1 and IKK-IκBα-NF-κB signaling pathways, including both IKKα and IKKβ, with similar potency. By means of high performance liquid chromatography analysis, it was estimated that PG490 constituted 1.27?±?0.06% of the total PG27 content. Further analysis demonstrated that compared to PG490 alone, PG27 that contained an equal amount of PG490 was less toxic and less immunosuppressive, suggesting the presence of cytoprotective ingredient(s) in the non-PG490 components of PG27. Conclusions In addition to demonstrating the immunomodulatory capacity of PG27 as the potential therapeutics for arthritis and prevention of transplantation rejection, the differential regulatory effects and mechanisms by PG27 and PG490 further support in part a possibly-existing Chinese herbal theory “Junn-Chenn-Zuou-SS”.
机译：背景技术几千年来，尚不清楚为什么中国人偏爱复杂的草药疗法，而很少尝试纯化这种草药。原因之一是他们认为中草药与西药相比毒性较低，而且耐受性更好。所谓的“ Junn-Chenn-Zuou-SS”理论说明了不同中草药结合产生的协同效应的概念。 PG27是从著名的抗风湿药雷公藤（Tutterygium wilfordii Hook f）（TwHf）中提炼的提取物，可有效减轻移植排斥反应并延长心脏异种移植物的存活期。方法对从血沉棕黄层分离的人原代T淋巴细胞进行实验。通过电泳确定kappaBα激酶抑制剂，kappaBα核因子kappaB（IKK-IκBα-NF-κB）和促分裂原激活蛋白激酶激活蛋白1（MAPK-AP-1）信号通路的活性。迁移率变化测定，免疫沉淀激酶测定，蛋白质印迹和转染测定。结果表明PG27抑制IKKα-IκBα-NF-κB和MAPK-AP-1信号通路。然而，IKKβ活性较不易受PG27抑制。相反，TwHf的纯化成分PG490（雷公藤内酯醇）具有相似的效价，同时降低了MAPK-AP-1和IKK-IκBα-NF-κB信号通路，包括IKKα和IKKβ。通过高效液相色谱分析，估计PG490占总PG27含量的1.27≤±0.06％。进一步的分析表明，与单独的PG490相比，包含等量PG490的PG27毒性更小且免疫抑制性更低，这表明PG27的非PG490组分中存在细胞保护成分。结论除了证明PG27作为关节炎的潜在疗法和预防移植排斥反应的免疫调节能力外，PG27和PG490的不同调节作用和机制还部分支持了可能存在的中草药理论“ Junn-Chenn-Zuou- SS”。

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