Antiarthritic mechanisms of amyrin triterpenes.

Abstract	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.
Authors	G Kweifio-Okai, F De Munk, B A Rumble, T A Macrides, M Cropley
Journal	Research communications in molecular pathology and pharmacology (Res Commun Mol Pathol Pharmacol) Vol. 85 Issue 1 Pg. 45-55 (Jul 1994) ISSN: 1078-0297 [Print] United States
PMID	7953194 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Esters Hydroxyeicosatetraenoic Acids Triterpenes Leukotriene B4 5-hydroxy-6,8,11,14-eicosatetraenoic acid Oleanolic Acid Collagenases beta-amyrin Indomethacin Methotrexate
Topics	Animals Arthritis, Experimental (drug therapy, metabolism) Cell Division (drug effects) Collagenases (drug effects) Esters (pharmacology) Female Humans Hydroxyeicosatetraenoic Acids (biosynthesis) Indomethacin (pharmacology) Leukotriene B4 (biosynthesis) Methotrexate (pharmacology) Neutrophils (drug effects, metabolism) Oleanolic Acid (analogs & derivatives) Rats Rats, Wistar Triterpenes (pharmacology) Tumor Cells, Cultured

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