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

Vu Thi Oanh; Nguyen Viet Phong; Byung Sun Min; Seo Young Yang; Jeong Ah Kim

doi:10.1080/14756366.2023.2251099

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

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2251099. doi: 10.1080/14756366.2023.2251099.

Authors

Vu Thi Oanh^{1

2}, Nguyen Viet Phong^{1

3}, Byung Sun Min⁴, Seo Young Yang⁵, Jeong Ah Kim^{1

3}

Affiliations

¹ Vessel-Organ Interaction Research Center, VOICE (MRC), College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea.
² Biotechnology Department, Vietnam - Korea Institute of Science and Technology, Thach Hoa, Thach That, Hanoi, Vietnam.
³ BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea.
⁴ College of Pharmacy, Drug Research and Development Center, Daegu Catholic University, Gyeongbuk, Republic of Korea.
⁵ Department of Pharmaceutical Engineering, Sangji University, Wonju, Republic of Korea.

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.

Keywords: Myristica fragrans; myrifragranone; myrifralignan; nutmeg; soluble epoxide hydrolase.

MeSH terms

Epoxide Hydrolases
Lignans* / pharmacology
Molecular Docking Simulation
Myristica*
Seeds

Substances

Epoxide Hydrolases
Lignans

Grants and 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).