Selective inducible nitric oxide synthase suppression by new bracteanolides from Murdannia bracteata

Abstract

Murdannia bracteata has been used as a Taiwanese folk medicine for its anti-inflammatory properties. However, neither its active ingredients nor its anti-inflammatory actions are well defined. Nitric oxide (NO), overproduced by activated macrophages via inducible NO synthase (iNOS), is suggested to be a significant pathogenic factor in various inflammatory tissue injuries. In order to elucidate the anti-inflammatory actions of M. bracteata, the present study was designed to isolate its active constituents and examine its effects on iNOS in lipopolysaccharide (LPS)-activated macrophages. Two new hydroxybutenolides, bracteanolide A ( 1) and B ( 2), together with (+)-( R)- p-hydroxyphenyllactic acid ( 3) and isovitexin ( 4), were isolated and identified from M. bracteata by the NO production assay . All of the compounds inhibited NO production except 3. Their rank order of potency was 1 > 2 > 4. Among these, 1 significantly inhibited NO production, which is associated with its suppression on iNOS induction in a concentration-dependent manner, with an IC 50 of 33.27 ± 0.86 μM. Nevertheless, isometric tension recordings in isolated endothelium-intact rat aorta revealed that 1–4 did not affect acetylcholine-induced endothelial NO-dependent relaxation, an index of endothelial NOS (eNOS) activity. The selective inhibition on iNOS provides a possible explanation for the anti-inflammatory use of M. bracteata.