Antiarthritic mechanisms of amyrin triterpenes.
The triterpenes, alpha-amyrin (AA) and its palmitate (AAP) and linoleate 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 triterpenes had no effect on the prostaglandin phase of carrageenin pedal edema in rats, which was reduced 28% by 100 microM IN. AAL caused a considerable reduction in the synthesis by human neutrophils of 5-lipoxygenase products--5-HETE (IC50 = 70 microM), LTB4, (62 microM), isomer I (30 microM) and isomer II (24 microM). Rat osteosarcoma cell growth was inhibited by all triterpenes with IC50's (microM) of < 10 (AAP), 14 (AA) and 27 (AAL) and were more effective than IN (35). MTX caused 100% inhibition at a concentration of 10 microM compared with 64% inhibition by AAP. Tadpole collagenase digestion of type I (bone) native collagen was completely inhibited by all the triterpenes as well as IN and MTX at 100 microM. The results indicate that the principal point of antiarthritic intervention by amyrin triterpenes lies in their local inhibition of joint destruction.
Department of Anatomy and Physiology, Royal Melbourne Institute of Technology, Bundoora, Australia.
G
G
Kweifio-Okai
F
F
De Munk
B A
BA
Rumble
T A
TA
Macrides
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M
Cropley
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D017364:Collagenases / Q000187:drug effects; D004952:Esters / Q000494:pharmacology; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis; D008727:Methotrexate / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004952:Esters; D006893:Hydroxyeicosatetraenoic Acids; D014315:Triterpenes; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D009828:Oleanolic Acid; D017364:Collagenases; C036380:beta-amyrin; D007213:Indomethacin; D008727:Methotrexate