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

Abstract

Two new neolignans, myrifralignans F–G (14 and 18), four new diarylnonanoid derivatives, myrifragranones A–D (21–24), and 18 known compounds were isolated and structurally elucidated from nutmeg (Myristica fragrans 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 (19 and 20) and four new compounds 21–24 displayed inhibitory activities against sEH, with IC₅₀ 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 in silico molecular docking and dynamics simulations. Our findings suggest that nutmeg could become a promising natural source for discovering and developing new sEH inhibitors.

Graphical abstract

Keywords:

• Myristica fragrans
• nutmeg
• myrifralignan
• myrifragranone
• soluble epoxide hydrolase

Author contributions

Vu Thi Oanh: Investigation, Writing- Original draft. Nguyen Viet Phong: Investigation, Writing- Original draft. Byung Sun Min: Resources. Seo Young Yang: Methodology, Software, Formal analysis, Writing-Review and Editing. Jeong Ah Kim: Conceptualisation, Writing-Review and Editing, Supervision.

Acknowledgements

The authors are thankful to the Korea Basic Science Institute – Daegu centre for the MS and CD measurement services.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

This research was supported by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (No. NRF-2020R1A5A2017323 and NRF-2022R1C1C1004636).