Activity of taraxasteryl acetate on inflammation and heat shock protein synthesis.
Pluchea sagittalis whole plant dichloromethane extract showed inhibitory activity in several inflammatory models: rat hind paw-edema, mice ear edema, and air-pouch rat granuloma. The extract inhibited the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in stimulated human neutrophils. It also showed inhibitory effect on heat shock protein 72 (hsp72) synthesis in stimulated neutrophils, while it had opposite effects on unstimulated cells. The triterpene taraxasteryl acetate was obtained from the dichloromethane extract by bioassay directed isolation, being active against induced ROS and RNS production in human neutrophils. In mice ear edema (induced by phorbol-12-mirystate-13-acetate, croton oil and arachidonic acid), taraxasteryl acetate showed a topical anti-inflammatory activity similar to the extract, but at 1/20 of the dose. The same ratio was observed for the inhibition of hsp72 production in stimulated human neutrophils. In unstimulated monocytes and neutrophils, taraxasteryl acetate showed a higher stimulating activity of hsp72 production than the extract, involving different mechanisms in each cell type. To our knowledge, taraxasteryl acetate is the first natural product for which a dual effect on the hsp response is reported.
Pérez-García
F
F
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal, 643, E-08028 Barcelona, Spain.
Marín
E
E
Parella
T
T
Adzet
T
T
Cañigueral
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016718:Arachidonic Acid; D019659:Asteraceae; D003436:Croton Oil; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D015745:Granuloma, Foreign-Body / Q000517:prevention & control*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018514:Plant Structures; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000096:biosynthesis; D017382:Reactive Oxygen Species; D013261:Sterols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013755:Tetradecanoylphorbol Acetate; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D010936:Plant Extracts; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013261:Sterols; D014315:Triterpenes; D016718:Arachidonic Acid; C092740:taraxasteryl acetate; D003436:Croton Oil; D013755:Tetradecanoylphorbol Acetate