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 (2–7, 9–22, and 41–52), including two neolignans, alongside various neolignan-diarylnonanoid, propenylbenzene-diarylnonanoid, 2,3-dimethylbutane-type lignan-diarylnonanoid, and monoterpene-diarylnonanoid conjugates, along with previously reported compounds (1, 8, and 23–40). Their chemical structures were determined via spectroscopic analyses. Compounds 2, 4, 9, 11, 12, 14, 17, and 18 exhibited potent inhibition of NF-κB/AP1 and IRF signaling induced by TLR agonists. Notably, stereoisomers showed distinct behavior, while 10R,11R-isomers induced cytotoxicity, and 10S,11R-isomers produced contrasting effects, especially within group-I compounds.