Anticholinesterases and antioxidant alkamides from <i>Piper nigrum</i> fruits

<p>The anticholinesterase and antioxidant effects of five different extracts of <i>Piper nigrum</i> were evaluated. Twenty-one known alkamides were isolated from active ethyl acetate extract and investigated for their cholinesterase inhibitory and antioxidant effects. Among them, piperine (<b>2</b>), piperettine (<b>5</b>) and piperettyline (<b>20</b>) exhibited dual inhibition against AChE and BChE, and feruperine (<b>18</b>) was the most potent selective inhibitor of BChE. Molecular docking simulation was performed to get insight into the binding interactions of the ligands and enzymes. In addition, <i>N</i>-trans-feruloyltyramine (<b>3</b>) contributed to the strongest DPPH radical-scavenging activity. The self-induced A<i>β</i> aggregation inhibition of <b>2</b>, <b>5</b> and <b>18</b> was further evaluated. Results indicated that some alkamides could be multifunctional lead candidates for Alzheimer’s disease therapy.</p>