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Betulin is a principal component of birch bark and is known to possess a broad range of biological activities, including antiinflammatory, antiviral and anticancer actions. The present study was carried out in vitro to clarify the influence of betulin on melanocortin (MC) receptor-ergic signalling by using COS-7 cells transfected with corresponding human MC receptor DNA. The results showed that betulin binds to the human melanocortin MC1, three to five receptors with selectivity to the MC1 subtype (K(i) value 1.022 +/- 0.115 microM). Betulin binds to the MC receptors with the following potency order-MC > MC3 > MC5 > MC4. Betulin itself does not stimulate cAMP generation, however, it slightly antagonizes alpha-melanocyte-stimulating hormone (alpha-MSH)-induced cAMP accumulation in the mouse melanoma cell line B16-F1. As a water-insoluble substance, betulin was dissolved in DMSO therefore DMSO competition with the labelled ligand NDP-MSH for the binding to the MC receptors was tested in the identical experimental set-up. We found that DMSO competes for binding to all the MC receptor subtypes, at 20% concentration and above. Selectivity for one or another receptor subtype was not observed. We have demonstrated for the first time, the ability of the plant compound betulin to bind to the MC receptors. One may suggest MC receptor MC1 subtype as the essential target for the antimelanoma action of betulin and its structurally close molecules such as betulinic acid. Moreover, we have found a new non-peptide small molecule MC mimetic, that is betulin. Thus, we report a new chemical motif for the binding to the MC receptors that could be used as a template for the search of more selective MC mimetics.

BACKGROUND: Berry pomaces contain biologically active substances and therefore may have considerable potential applications in food and pharmaceutical industries. However, there is a lack of studies on extracting these valuable products from berry pomaces. OBJECTIVE: This study aims to evaluate major constituents of five Vaccinium spp. berry pomace extracts and investigate their antioxidant, hypoglycaemic and hepatoprotective properties. METHODS: Total anthocyanin, procyanidin and polyphenol contents in berry residues were measured by spectrophotometric pH-differential, 4-dimethylaminocinnamaldehyde and Folin-Ciocalteu method, respectively. Identification and quantification of separate compounds were assessed by ultra-performance liquid chromatography and liquid chromatography-time-of-flightmasspectroscopy. Anti-hyperglycaemic properties of pomace extracts were evaluated based on inhibition of ␣-amylase and ␣-glucosidase activity. Extract hepatoprotective effects were estimated based on increased human hepatic cell line HepG2 viability in oxidative stress conditions. RESULTS:The extracts possessed strong antioxidant effects and efficacy for inhibiting the activities of enzymes involved in carbohydrate digestion and for protecting hepatic cells from oxidative damage. CONCLUSIONS: Hepatoprotective and hypoglycaemic properties of berry pomace extracts may be due to the presence of active polyphenols and their synergistic effects. Our results support the use of berry pomaces for designing standardised formulations for the prevention of chronic diseases associated with oxidative stress.