'In vitro' antioxidant and photoprotective properties and interaction with model membranes of three new quercetin esters.

Quercetin is well known to possess the strongest protective effect against UV light-induced lipoperoxidation. However, the absolute water insolubility of quercetin is a key step that may limit its bioavailability and, thus, its 'in vivo' employment as a photoprotective agent. The aim of the present paper was to evaluate 'in vitro' the antioxidant and photoprotective properties and the interaction with model membranes of three new semisynthetic quercetin derivatives, quercetin-3-O-acetate (Q-ac), quercetin-3-O-propionate (Q-pr) and quercetin-3-O-palmitate (Q-pal), obtained by esterification of the C-3 OH function with an aliphatic side-chain of different length. The antioxidant activity of quercetin and of its three esters was assessed in two 'in vitro' experimental models: (a) the bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical; (b) UV radiation-induced peroxidation in multilamellar vesicles (MLVs). Differential scanning calorimetry on dimyristoylphosphatidylcholine MLVs and unilamellar vesicles was employed to investigate the interaction of the drugs tested with model membranes. Finally, the stability following UV light exposure and the lipophilicity and water solubility of quercetin and its three esters were examined. The findings obtained demonstrated that the esterification with an opportune aliphatic side chain of the OH function located at the C-3 position allows the production of new quercetin derivatives, which may be good candidates as photoprotective agents. In particular, one could speculate that the esterification with a short side-chain (such as in Q-ac and Q-prop) provides the suitable chemico-physical features not only to maintain the antioxidant and photoprotective effectiveness of the parent drug, but also to be able to migrate through the aqueous environment and to interact with and cross phospholipid membranes.

Interaction of melatonin with model membranes and possible implications in its photoprotective activity.

It is well known that administration of antioxidants represents a successful strategy for preventing the occurrence and for reducing the severity of UV-mediated oxidative damage. Melatonin was recently shown to be an efficacious photoprotective agent. The aim of the present study was to better investigate the interaction of melatonin with model membranes and the possible implications in its photoprotective activity. The antioxidant activity of melatonin was tested in two 'in vitro' experimental models: (a) UV radiation-induced peroxidation in phosphatidylcholine multilamellar vesicles (MLVs); (b) scavenging activity against nitric oxide (NO). Furthermore, we investigated the melatonin/biomembrane interaction by differential scanning calorimetry (DSC) on dimyristoylphosphatidylcholine (DMPC) MLVs and unilamellar vesicles (LUVs). The findings of in vitro antioxidant tests suggest that the photoprotective effect of melatonin should be due, partially at least, to the drug scavenging activity against aqueous and lipophilic free radicals, including NO; besides, melatonin might provide its protective effect against UV radiation-induced damage also by acting as a UV-absorbing screen. The results of DSC experiments have evidenced a good capability of melatonin to interact with DMPC bilayers, causing a significant fluidifying effect; however, the transfer of melatonin in the LUVs is faster than that observed for MLVs, even if both values tend to the maximum values reachable. Our present data allow us to emphasize two points: (1) the fluidifying effect induced by melatonin on lipidic bilayers might act as a cooperative mechanism in its protective effect against peroxidative membrane damage; (2) melatonin appears able to cross biomembranes, so that it could protect intracellular components against peroxidative insult.