New insights into the mechanism of action of the anti-inflammatory triterpene lupeol

The pentacyclic triterpene lupeol has been studied for its inhibitory effec ts on murine models of inflammation and peritoneal macrophage functions in- vitro. Lupeol (0.5 and 1 mg/ear) administered topically suppressed the mous e ear oedema induced by 12-O-tetradecanoylphorbol acetate (TPA), being less effective on ear oedema induced by arachidonic acid. Quantitation of the n eutrophil specific marker myeloperoxidase demonstrated that its topical act ivity was associated with reduction in cell infiltration into inflamed tiss ues. When tested invitro, lupeol significantly reduced prostaglandin E-2 (P GE(2)) production from A23187-stimulated macrophages, but failed to affect leukotriene C-4 release. It was a weak inhibitor of nitrite release, but do se-dependently suppressed PGE(2). Cytokine production (tumour necrosis fact or alpha and interleukin-1 beta was inhibited in the range 10-100 mum in li popolysaccharide-treated macrophages. This study demonstrated that lupeol p ossessed anti-inflammatory activity which was likely to depend on its abili ty to prevent the production of some mediators.