Fatty acid synthase inhibitors from the hulls of Nephelium lappaceum L.

Natural products inhibiting fatty acid synthase (FAS) are appearing as potential therapeutic agents to treat cancer and obesity. The bioassay-guided chemical investigation of the hulls of Nephelium lappaceum L. resulted in the isolation of ten compounds (1–10) mainly including flavonoids and oleane-type triterpene oligoglycosides, in which all of the compounds were isolated from this plant for the first time. Additionally, compounds 8 and 9 were new hederagenin derivatives and were elucidated as hederagenin 3-O-(2,3-di-O-acetyl-α-l-arabinofuranosyl)-(1→3)-[α-l-rhamnopyranosyl(1→2)]-β-l-arabinopyranoside and hederagenin 3-O-(3-O-acetyl-α-l-arabinofuranosyl)-(1→3)-[α-l-rhamnopyranosyl-(1→2)]-β-l-arabinopyranoside, respectively. All these isolates were evaluated for inhibitory activities of FAS, which showed these isolates had inhibitory activity against FAS with IC50 values ranging from 6.69 to 204.40 μM, comparable to the known FAS inhibitor EGCG (IC50 = 51.97 μM). The study indicates that the hulls of Nephelium lappaceum L. could be considered as potential sources of promising FAS inhibitors and the oleane-type triterpene oligoglycosides could be considered as another type of natural FAS inhibitors.

Graphical abstractTwo new oleane-type triterpene oligoglycosides, as well as eight known compounds, were isolated from the hulls of Nephelium lappaceum L. and all these isolates exhibited activities against fatty acid synthase.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights►Nephelium lappaceum hulls could be potential sources of promising FAS inhibitors. ► Ten compounds from Nephelium lappaceum hulls had the inhibition activity to FAS. ► Two new oleane-type triterpene oligoglycosides with acetyl groups were identified. ► Oleane-type triterpene oligoglycosides were another type of natural FAS inhibitors. ► Acetyl groups may be a positive factor and are required for the activity of FAS.