5α-reductase inhibitory tannin-related compounds isolated from Shorea laeviforia

Five tannin-related compounds - gallic acid, flavogallonic acid dilactone, valoneic acid dilactone, gallagyldilactone, ellagic acid - were isolated from the heartwood of Shorea laevifbria, and the inhibitory activity of each against rat liver 5alpha-reductase was evaluated. Valoneic acid dilactone and gallagyldilactone exhibited positive inhibitory activity, but gallic acid and ellagic acid did not. Flavogallonic acid dilactone stimulated 5alpha-reductase activity, even though this compound is structurally similar to valoneic acid dilactone. The kinetic study of valoneic acid dilactone and gallagyldilactone indicated that the inhibitory behavior of 5alpha-reductase were not competitive against the substrate (testosterone) and were partially competitive against the cofactor (NADPH). Additionally, double inhibition analysis of valoneic acid dilactone and NADP(+) showed synergetic inhibition. These results suggested that neither valoneic acid dilactone nor gallagyldilactone can affect the binding of testosterone but that either compound could interact with an enzyme-NADP(+) complex to inhibit 5alpha-reductase.