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

Abstract	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.
Authors	G Krishna, K Liu, H Shigemitsu, M Gao, T A Raffin, G D Rosen
Journal	The American journal of pathology (Am J Pathol) Vol. 158 Issue 3 Pg. 997-1004 (Mar 2001) ISSN: 0002-9440 [Print] United States
PMID	11238047 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Diterpenes Drugs, Chinese Herbal Epoxy Compounds Immunosuppressive Agents Phenanthrenes RG 490-88 Transforming Growth Factor beta Bleomycin triptolide
Topics	Animals Bleomycin Bronchoalveolar Lavage Fluid (chemistry) Cell Survival Diterpenes (chemistry, pharmacology, therapeutic use) Drugs, Chinese Herbal (chemistry, therapeutic use) Epoxy Compounds Fibroblasts (cytology, metabolism) Immunosuppressive Agents (chemistry, therapeutic use) Inflammation (pathology) Lung (cytology, metabolism, pathology) Male Mice Mice, Inbred C57BL Phenanthrenes Pulmonary Fibrosis (chemically induced, drug therapy, genetics, pathology) Transcription, Genetic (drug effects) Transforming Growth Factor beta (genetics, metabolism)

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