Ho Ling-Jun, Chang Wen-Liang, Chen Ann, Chao Ping, Lai Jenn-Haung
Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan, R, O, C.
J Transl Med. 2013 Nov 21;11:294. doi: 10.1186/1479-5876-11-294.
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.
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.
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.
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".
数千年来，中国人为何偏爱复方草药且很少尝试提纯，原因尚不明晰。其中一个原因是，他们认为与西药相比，中药的毒性相对较小且耐受性更好。所谓的“君臣佐使”理论阐释了不同中药组合产生协同作用的概念。PG27是从著名的抗风湿中药雷公藤（Tripterygium wilfordii Hook f, TwHf）中提取的精制提取物，在减轻移植排斥反应和延长心脏异种移植存活时间方面具有疗效。
实验在从血沉棕黄层分离出的人原代T淋巴细胞中进行。通过电泳迁移率变动分析、免疫沉淀激酶分析、蛋白质免疫印迹法和转染分析，测定κB激酶抑制剂 - κBα抑制剂 - 核因子κB（IKK - IκBα - NF - κB）和丝裂原活化蛋白激酶 - 活化蛋白1（MAPK - AP - 1）信号通路的活性。
我们发现PG27抑制IKKα - IκBα - NF - κB和MAPK - AP - 1信号通路；然而，IKKβ的活性对PG27的抑制作用不太敏感。相比之下，TwHf的纯化成分PG490（雷公藤内酯醇）对MAPK - AP - 1和IKK - IκBα - NF - κB信号通路均有抑制作用，对IKKα和IKKβ的抑制效力相似。通过高效液相色谱分析估计，PG490占PG27总含量的1.27±0.06%。进一步分析表明，与单独的PG490相比，含有等量PG490的PG27毒性更小且免疫抑制作用更弱，这表明PG27的非PG490成分中存在细胞保护成分。
除了证明PG27作为关节炎潜在治疗药物和预防移植排斥反应的免疫调节能力外，PG27和PG490的不同调节作用及机制部分地进一步支持了可能存在的中药理论“君臣佐使”。
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