Extract Potentiates the Effect of Melatonin on Human Melatonin MT and MT Receptors with Functional Selectivity.

Melatonin is a tryptophan derivative synthesized in plants and animals. In humans, melatonin acts on melatonin MT and MT receptors belonging to the G protein-coupled receptor (GPCR) family. Synthetic melatonin receptor agonists are prescribed for insomnia and depressive and circadian-related disorders. Here, we tested 25 commercial plant extracts, reported to have beneficial properties in sleep disorders and anxiety, using cellular assays (2─[I]iodomelatonin binding, cAMP inhibition, ERK1/2 activation and β-arrestin2 recruitment) in mock-transfected and HEK293 cells expressing MT or MT. Various melatonin receptor-dependent and -independent effects were observed. Extract 18 () from dried fruits stood out with very potent effects in melatonin receptor expressing cells. The high content of endogenous melatonin in (5.28 ± 0.46 mg/g extract) is consistent with this observation. contains an additional active principle that potentiates the effect of melatonin on G protein-dependent pathways but not on β-arrestin2 recruitment. Further active principles potentiating exogenous melatonin were detected in several extracts. In conclusion, we identified plant extracts with various effects in GPCR-based binding and signalling assays and identified high melatonin levels and a melatonin-potentiating activity in dried fruit extracts that might be of therapeutic potential.