Inhibition of type II collagen-induced arthritis in rats by triptolide.
The effects of purified triptolide, a diterpenoid triepoxide compound derived from the Chinese traditional anti-rheumatic medicinal plant extract, Tripterygium wilfordii Hook f (TWHf), were determined in type II collagen-induced arthritis (CIA) in rats. Lewis rats were immunized with bovine type II collagen and treated with purified triptolide 0.1 mg/kg/day or control (vehicle for triptolide) by daily gavage feedings for 28 days. Triptolide was well-tolerated with no evidence of toxicity. Treatment with triptolide resulted in significant delay in time to onset of arthritis (P = 0.039), as well as significantly decreased arthritis incidence (P = 0.024), clinical arthritis severity score (P < 0.0001), histopathological arthritis severity score (P < 0.0001), and in vivo cell-mediated immunity to collagen (P = 0.0004). Triptolide appeared to be a potent immunomodulatory inhibitor of CIA in rats and this may account for the previously observed anti-rheumatic properties of crude extracts of TWHf, although more extensive studies will be needed to confirm these effects.
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Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Brandwein
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D002417:Cattle; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000276:immunology; D004224:Diterpenes / Q000627:therapeutic use*; D004852:Epoxy Compounds; D005260:Female; D006614:Hindlimb; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D010616:Phenanthrenes; D010865:Pilot Projects; D051381:Rats; D011917:Rats, Inbred Lew
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; C001899:triptolide; D003094:Collagen