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

Abstract

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-kappa B/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.