<jats:title>Abstract</jats:title><jats:p>From the stems of <jats:italic>Fissistigma bracteolatum</jats:italic>, a novel natural product with an unprecedented skeleton, bractelactone (<jats:bold>1</jats:bold>), was isolated, together with four known compounds: piperolactam A (<jats:bold>2</jats:bold>), aristololactam BIII (<jats:bold>3</jats:bold>), aristololactam BII (<jats:bold>4</jats:bold>), and fissilandione (<jats:bold>5</jats:bold>). The structure of <jats:bold>1</jats:bold> was established on the basis of spectroscopic data as (3<jats:italic>Z</jats:italic>)‐6,7‐dihydroxy‐4‐methoxy‐3‐(phenylmethylidene)‐5‐(3‐phenylpropanoyl)‐1‐benzofuran‐2(3<jats:italic>H</jats:italic>)‐one. This compound may be derived from a hybrid of a chalcone and a cinnamic acid, or from a degradation product of a dichalcone. Compounds <jats:bold>1, 2</jats:bold>, and <jats:bold>5</jats:bold> showed inhibitory effects on NO generation by RAW264.7 macrophages in response to lipopolysaccharide. Compounds <jats:bold>2</jats:bold> and <jats:bold>5</jats:bold> showed inhibitory effects on formyl‐<jats:sc>L</jats:sc>‐methionyl‐<jats:sc>L</jats:sc>‐leucyl‐<jats:sc>L</jats:sc>‐phenylalanine (fMLP)‐induced superoxide anion (O<jats:styled-content>$\rm{_{2}^{{^\cdot} -}}$</jats:styled-content>) generation in human neutrophils.