Biol. Pharm. Bull., 24(2),167-171, February 2001

Savinin, a Lignan from Pterocarpus santalinus Inhibits Tumor Necrosis Factor-aProduction and T Cell Proliferation

Jae Youl CHO,*, a, b Jisoo PARK,a Pyoung Su KIM,a Eun Sook YOO,a Kyong Up BAIK,a and Myung Hwan PARK a

R & D Center, Daewoong Pharmaceutical Co., Ltd.,a Sungnam 462-120, Korea and Department of Immunology, Windeyer Institute of Medical Sciences, University College London Medical School,b London W1P 6DB, United Kingdom.

Two lignans were isolated from the heartwood of Pterocarpus santalinus by activity-guided fractionation and investigated for their biological properties and molecular mechanism of action. On the basis of their spectro-scopic data, these compounds were identified as savinin (1) and calocedrin (2), dibenzyl butyrolactone-type lignan compounds having an a-arylidene g-lactone structure. These lignans significantly inhibited tumor necrosis factor (TNF)-a 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 was confirmed to be mediated by the non-polar butyrolactone ring, according to a structure-relation-ship study with structurally related and unrelated compounds, such as arctigenin (a dibenzyl butyrolactone type lignan), eudesmin (a furofuran type lignan), isolariciresinol (a dibenzylbutane type lignan), and cynaropicrin (a sesquiterpene lactone). The results suggest that savinin may act as an active principle in the reported biological activities of P. santalinus, such as antiinflammatory effect, by mediation of the butyrolactone ring as a valuable pharmacophore.

Key words Pterocarpus santalinus; savinin; tumor necrosis facro- aproduction; T cell proliferation