Savinin, a lignan from Pterocarpus santalinus inhibits tumor necrosis factor-alpha production and T cell proliferation

Two lignans were isolated fram the heartwood of Pterocarpus santalinus by a ctivity-guided fractionation and investigated for their biological properti es and molecular mechanism of action. On the basis of their spectroscopic d ata, these compounds were identified as savinin (1) and calocedrin (2), dib enzyl butyrolactone-type lignan compounds having an alpha -arylidene gamma -lactone structure. These lignans significantly inhibited tumor necrosis fa ctor (TNF)-alpha production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and T cell proliferation elicited by concanavalin (Con A), without displaying cytotoxicity. The molecular inhibitory mechanism of compound 1 w as confirmed to be mediated by the non-polar butyrolactone ring, according to a structure-relationship study with structurally related and unrelated c ompounds, such as arctigenin (a dibenzyl butyrolactone type lignan), eudesm in (a furofuran type lignan), isolariciresinol (a dibenzylbutane type ligna n), and cynaropicrin (a sesquiterpene lactone). The results suggest that sa vinin may act as an active principle in the reported biological activities of P. santalinus, such as antiinflammatory effect, by mediation of the buty rolactone ring as a valuable pharmacophore.