Cistifolin, an Integrin-Dependent Cell Adhesion Blocker from the Anti-Rheumatic Herbal Drug, Gravel Root (Rhizome of Eupatorium purpureum)

Abstract

During routine screening of medicinal plants for small molecular weight inhibitors of cell adhesion, the crude ethanolic extract of the anti-rheumatic herbal drug gravel root (rhizome of Eupatorium purpureum), was identified as a potent inhibitor of some β1 and β2 integrin-mediated cell adhesions. The active principle of gravel root has now been isolated and identified as 5-acetyl-6-hydroxy-2,3-dihydro-cis-2-isopropenyl-3-tiglinoyloxybenzofuran (1). Compound 1 inhibited integrindependent cell-cell and cell-protein interactions in vitro with EC₅₀ values between 7-20 µg/ml. As with indomethacin, 1 administered orally two hours before induction of inflammation (in rat paw) by carrageenan inhibited oedema formation in a dose (10 and 50 mg/kg)-dependent manner. It appears that 1 has therapeutic potential for diseases where integrin adhesion molecules play a significant role.