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 10 R ,11 R -isomers induced cytotoxicity, and 10 S ,11 R -isomers produced contrasting effects, especially within group-I compounds.