ANTIARTHRITIC MECHANISMS OF AMYRIN TRITERPENES

The triterpenes, alpha-amyrin (AA) and its palmitate (AAP) and linolea te esters (AAL), were tested on models of inflammatory and destructive arthritic processes and their effects were compared with the clinical antiarthritic drugs indomethacin (IN) and methotrexate (MTX). The tri terpenes had no effect on the prostaglandin phase of carrageenin pedal edema in rats, which was reduced 28% by 100 mu M IN. AAL caused a con siderable reduction in the synthesis by human neutrophils of 5-lipoxyg enase products - 5-HETE (IC50 = 70 mu M), LTB(4), (62 mu M), isomer I (30 mu M) and isomer II (24 mu M). Rat osteosarcoma cell growth was in hibited by all triterpenes with IC50's (mu M) of < 10 (AAP), 14 (AA) a nd 27 (AAL) and were more effective than IN (35). MTX caused 100% inhi bition at a concentration of 10 mu M compared with 64% inhibition by A AP. Tadpole collagenase digestion of type I (bone) native collagen was completely inhibited by all the triterpenes as well as IN and MTX at 100 mu M. The results indicate that the principal point of antiarthrit ic intervention by amyrin triterpenes lies in their local inhibition o f joint destruction.