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

The pentacyclic triterpene lupeol has been studied for its inhibitory effects on murine models of inflammation and peritoneal macrophage functions in-vitro. Lupeol (0.5 and 1 mg/ear) administered topically suppressed the mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate (TPA), being less effective on ear oedema induced by arachidonic acid. Quantitation of the neutrophil specific marker myeloperoxidase demonstrated that its topical activity was associated with reduction in cell infiltration into inflamed tissues. When tested invitro, lupeol significantly reduced prostaglandin E-2 (PGE(2)) production from A23187-stimulated macrophages, but failed to affect leukotriene C-4 release. It was a weak inhibitor of nitrite release, but dose-dependently suppressed PGE(2). Cytokine production (tumour necrosis factor alpha and interleukin-1 beta was inhibited in the range 10-100 mum in lipopolysaccharide-treated macrophages. This study demonstrated that lupeol possessed anti-inflammatory activity which was likely to depend on its ability to prevent the production of some mediators.