PG490-88, a derivative of triptolide, blocks bleomycin-induced lung fibrosis

In this study we evaluate the antifibrotic properties of PG-490-88, a water -soluble derivative of triptolide. Triptolide is an oxygenated diterpene th at is derived from a traditional Chinese herb that has potent immunosuppres sive and antitumor activity. We used the intratracheal bleomycin mouse mode l and found that PG490-88 inhibits fibrosis in the bleomycin group when giv en the same day or 5 days after bleomycin. PG490-88 also markedly reduced t he number of myofibroblasts in the bleomycin treatment group. An enzyme-lin ked immunosorbent assay of transforming growth factor (TGF)-beta in the bro nchoalveolar lavage fluid showed a significant decrease in TGF-beta in the PG490-88-treated groups compared to the bleomycin-treated group. Additional ly, triptolide blocked bleomycin-induced increase in TGF-beta mRNA in cultu red normal human lung fibroblasts. The efficacy of PG490-88 when administer ed late after bleomycin installation suggests a potential role in the treat ment of idiopathic pulmonary fibrosis.