Immunochemical characterization of the functional constituents of Tripterygium wilfordii contributing to its anti-inflammatory property.

1. Tripterygium wilfordii (TW) contains bioactive compounds that possess immunosuppressive properties. These compounds are considered to be potential drugs in the treatment of acute graft rejections. However, their structure-activity relationships remain unknown. 2. The aim of the present study was to delineate the molecular moieties of triptolide that could account for its ability to inhibit inflammatory responses. In this context, purified TW active compounds (triptolide and triptonide) and synthetic triptolide derivatives were prepared to investigate the structure-activity relationships of triptolide. To this end, rat splenocytes were treated with increasing concentrations of the compounds and then allogenically stimulated using a mixed lymphocyte reaction to determine their antiproliferative activities. From the results, the IC50 value of each compound was calculated. 3. Modification of the beta-hydroxyl group at the C-14 position of the triptolide molecule significantly affected the immunosuppressive activity of T59, as demonstrated by a sevenfold increase of the IC50. Conversely, reduction of the gamma-butyrolactone group in T60 and T61 completely abrogated the antiproliferative effect. Alterations in the C-14 beta-hydroxyl and gamma-butyrolactone groups also resulted in reduced cytotoxicity. 4. The present findings demonstrate that the C-14 beta-hydroxyl and gamma-butyrolactone moieties of the triptolide molecule are crucial for its anti-inflammatory properties and cytotoxicity and are responsible for the compound's antiproliferative activity.