Phenylpropanoids and neolignans isolated from Myristica fragrans enhance glucose uptake in myotubes

Nutmeg is the seed of Myristica fragrans or its powder and is used as a spice and a traditional medicine. The antidiabetic effect of nutmeg is not fully understood yet. In this study, we examine the isolation and identification of the active compounds of Myristica fragrans with regards to glucose uptake and elucidate their mechanism in L6 myotubes. Myrisiticin, licarin B, erythro-2-(4-allyl-2,6-dimethoxy-phenoxy)-1-(3,4-dimethoxyphenyl)-propan-1-ol (ADDP) and (7S,8R)-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4,5-trimethoxyphenyl)-propan-1-ol (ADTP) were isolated and identified as the active compounds. Myristicin or a mixture of ADDP and ADTP promoted the translocation of glucose transporter 4 (GLUT4) through phosphorylation of AMP-activated protein kinase in L6 myotubes 15 min after treatment, while licarin B promoted it 240 min after treatment. Oral administration of the fraction from Myristica fragrans containing these active compounds to ICR mice suppressed post-prandial hyperglycemia. Thus, Myristica fragrans is a promising functional food to prevent post-prandial hyperglycemia and type 2 diabetes mellitus by promoting glucose uptake in muscle.