Dihydro-β-agarofuran-type sesquiterpenoids from the seeds of Tripterygium wilfordii (Thunder God Vine) and evaluation of their anti-osteoclastogenesis and immunosuppressive activities

Extensive phytochemical investigation of the seeds of Tripterygium wilfordii led to the identification of 54 polyesterified dihydro-beta-agarofuran-type sesquiterpenoids, including 27 previously undescribed ones, named Trip-wilin I-XXVII (1-27). Comprehensive spectroscopic and single-crystal X-ray diffraction analyses, along with electronic circular dichroism (ECD) calculations were used for the structural elucidation of the new compounds. Biological assay revealed that 37 compounds among the isolates exhibited significant inhibition against osteoclastogenesis induced by receptor activator of nuclear factor -KB ligand (RANKL) at 10 mu M. Further investigation indicated that Triptogelin C-3 (54), with the most potent osteoclastogenesis inhibitory activity, regulated the osteoclast marker genes (MMP-9, c-Fos, CTSK, and TRAP) and proteins in a dose-dependent manner in vitro. Besides, celaforin D-1 (28), 1 alpha,6 beta,15-triacetoxy-8 alpha,9 alpha-dibenzoyloxy-2 alpha-hydroxydihydro-beta-agarofuran (34), triptogelin A-2 (37), and chiapen D (49) showed moderate suppressive effects on the proliferation of T and B lymphocytes with IC50 values ranging between 8.1 +/- 0.8 and 19.0 +/- 0.9 mu M.