leukotriene-b4 and beta-amyrin

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.

Topics: Animals; Arthritis, Experimental; Cell Division; Collagenases; Esters; Female; Humans; Hydroxyeicosatetraenoic Acids; Indomethacin; Leukotriene B4; Methotrexate; Neutrophils; Oleanolic Acid; Rats; Rats, Wistar; Triterpenes; Tumor Cells, Cultured

Triterpenes--alpha-amyrin acetate, beta-amyrin acetate and beta-amyrin were tested for their effects on the synthesis of 5-lipoxygenase products in human neutrophils. All the triterpenes reduced 5-HETE synthesis without effect on LTB4 synthesis. The relative effects suggest that 5-HETE inhibition can explain the antiarthritic activity possessed by these compounds.

Topics: Female; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Leukotriene B4; Lipoxygenase Inhibitors; Neutrophils; Oleanolic Acid; Triterpenes