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Here, we report the investigation of the dichloromethane-soluble fraction obtained in a 0.24% m/m yield from the hot water extract of mulberry leaves. A significant, dose-dependent activity was found by means of the 24-h glucose consumption of fully differentiated adipocytes both in the absence and presence of insulin. The fraction was characterized by HPLC-DAD, GC-MS and GC-FID. The main constituent (40.3% by means of GC-FID) was isolated and identified as loliolide by EIMS, HRESIMS and NMR spectroscopy. In the active fraction benzyl alcohol, ethyl benzoate, t-cinnamic acid, p-hydroxyacetophenone, t-coniferyl alcohol and synapil alcohol were also identified by GC-MS and quantified by GC-FID (0.7, 1.3, 1.5, 2.9, 7.5 and 2.6%, respectively). 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