Insights into the inhibitory activities of neolignans and diarylnonanoid derivatives from nutmeg ( Myristica fragrans Houtt.) seeds on soluble epoxide hydrolase using in vitro and in silico approaches.

Two new neolignans, myrifralignans F-G ( and ), four new diarylnonanoid derivatives, myrifragranones A-D (-), and 18 known compounds were isolated and structurally elucidated from nutmeg ( Houtt.) seeds. The absolute configurations of these secondary metabolites were determined using the electronic circular dichroism technique. The inhibitory potential of these isolated compounds on soluble epoxide hydrolase (sEH) was investigated for the first time. Among them, malabaricones B and C ( and ) and four new compounds - displayed inhibitory activities against sEH, with IC values ranging from 14.24 to 46.35 µM. Additionally, the binding mechanism, key binding interactions, stability, and dynamic behaviour of the active compounds with the sEH enzyme were analysed using molecular docking and dynamics simulations. Our findings suggest that nutmeg could become a promising natural source for discovering and developing new sEH inhibitors.