Melanin-concentrating hormone-1 receptor antagonism and anti-obesity effects of ethanolic extract from Morus alba leaves in diet-induced obese mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In Korea, Morus alba leaves have been traditionally administered as natural therapeutic agent for the alleviating dropsy and diabetes. AIM OF THE STUDY: The present study was performed to evaluate melanin-concentrating hormone receptor subtype 1 (MCH1) antagonism of the ethanol extract of Morus alba leaves (EMA) and its anti-obesity effect in diet-induced obese (DIO) mice. MATERIALS AND METHODS: The binding affinity of EMA for the MCH1 receptor with europium-labeled MCH (Eu-MCH), the function of recombinant MCH1 receptors expressed in CHO cells, and the anti-obesity effects in DIO mice were evaluated. RESULTS: MCH1 receptor binding studies showed, EMA exhibited a potent inhibitory activity with IC50 value of 2.3+/-1.0 microg/ml. EMA (10-100 microg/ml) also inhibited the intracellular calcium mobilization with the recombinant MCH1 receptors expressed in CHO cells. In an anti-obesity study with DIO mice, longterm oral administrations of EMA for 32 consecutive days produced a dose-dependent decrease in body weight and hepatic lipid accumulation. CONCLUSIONS: These results suggest that chronic treatment with EMA exerts an anti-obesity effect in DIO mice, and its direct MCH1 receptor antagonism may contribute to decrease body weight.