title: 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".
abstract: 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".
authors.forename: Ling-Jun
authors.initials: LJ
authors.lastname: Ho
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Chang
authors.forename: Ann
authors.initials: A
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Chao
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan, R, O, C. laiandho@gmail.com.
authors.forename: Jenn-Haung
authors.initials: JH
authors.lastname: Lai
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy*; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D024202:Electrophoretic Mobility Shift Assay; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D059748:Proteolysis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects*; D029757:Tripterygium / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D017931:DNA Primers; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D010936:Plant Extracts; C001899:triptolide; D051550:I-kappa B Kinase