Neolignans and Diarylnonanoid Derivatives with Anti-inflammatory Activity from Myristica fragrans Houtt. Seeds

Myristica fragrans Houtt. is rich in lignans, neolignans, and diarylnonanoids, with well-documented anti-inflammatory properties. However, there is limited research on the conjugated forms of diarylnonanoids, neolignans, monoterpenes, and others and their anti-inflammatory effects. Our study isolated 33 new compounds (<b>2</b>–<b>7, 9</b>–<b>22</b>, and <b>41</b>–<b>52</b>), including two neolignans, alongside various neolignan-diarylnonanoid, propenylbenzene-diarylnonanoid, 2,3-dimethylbutane-type lignan-diarylnonanoid, and monoterpene-diarylnonanoid conjugates, along with previously reported compounds (<b>1</b>, <b>8</b>, and <b>23</b>–<b>40</b>). Their chemical structures were determined via spectroscopic analyses. Compounds <b>2</b>, <b>4</b>, <b>9</b>, <b>11</b>, <b>12</b>, <b>14</b>, <b>17</b>, and <b>18</b> exhibited potent inhibition of NF-κB/AP1 and IRF signaling induced by TLR agonists. Notably, stereoisomers showed distinct behavior, while 10<i>R</i>,11<i>R</i>-isomers induced cytotoxicity, and 10<i>S</i>,11<i>R</i>-isomers produced contrasting effects, especially within group-I compounds.