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 that is derived from a traditional Chinese herb that has potent immunosuppressive and antitumor activity. We used the intratracheal bleomycin mouse model and found that PG490-88 inhibits fibrosis in the bleomycin group when given the same day or 5 days after bleomycin. PG490-88 also markedly reduced the number of myofibroblasts in the bleomycin treatment group. An enzyme-linked immunosorbent assay of transforming growth factor (TGF)-beta in the bronchoalveolar lavage fluid showed a significant decrease in TGF-beta in the PG490-88-treated groups compared to the bleomycin-treated group. Additionally, triptolide blocked bleomycin-induced increase in TGF-beta mRNA in cultured normal human lung fibroblasts. The efficacy of PG490-88 when administered late after bleomycin installation suggests a potential role in the treatment of idiopathic pulmonary fibrosis.
Krishna
G
G
Division of Pulmonary and Critical Care Medicine, Stanford University School of Medicine, 300 Pasteur Dr., Stanford, CA 94305-5236, USA.
Liu
K
K
Shigemitsu
H
H
Gao
M
M
Raffin
T A
TA
Rosen
G D
GD
D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002470:Cell Survival; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D004852:Epoxy Compounds; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010616:Phenanthrenes; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; C423084:RG 490-88; D016212:Transforming Growth Factor beta; D001761:Bleomycin; C001899:triptolide