The effects of natural polyphenols, resveratrol (RES) and dihydroquercetin (DHQ), included in phospholipid nanoparticles, have been compared with free substances of RES and DHQ in in vitro and in vivo experiments. Preincubation of healthy donor plasma low density lipoproteins (LDL) with RES or DHQ included in phospholipid nanoparticles caused a more pronounced decrease in Cu2+ induced lipid oxidation compared with the free substances, and reduced the formation of lipid peroxides products. Bioavailabilities of RES and DHQ in phospholipid formulations after oral administration in rats were increased by 1.5-2 times. In an acute hypoxia model in mice prophylactic two-week administration of RES or DHQ phospholipid formulations resulted in 25% increase in survival and 1.5-fold increase in catalase activity in brain homogenates compared to free substances. Using the model of endothelial dysfunction in rats induced by L-NAME it was shown, that RES markedly attenuated the inhibition effect of L-NAME on NO synthesis. RES in phospholipid nanoparticles had the same action at a dose 10 times lower compared to free RES. Load test with resistance (clamping of the ascending aorta for 30 sec) showed that phospholipid formulation of RES possessed more pronounced protective effect due to the stimulation of endothelial NO-synthase.
Issledovali biodostupnost' i aktivnost' kompozitsii prirodnykh polifenolov – resveratrola (RES) i digidrokvertsetina (DGK) – v sostave fosfolipidnykh nanochastits. Sravnenie spetsificheskikh svoĭstv RES i DGK v sostave kompozitsiĭ so svoĭstvami sootvetstvuiushchikh svobodnykh substantsiĭ provodili v éksperimentakh in vitro i in vivo. Predvaritel'naia inkubatsiia lipoproteinov nizkoĭ plotnosti (LNP) iz plazmy krovi zdorovogo donora s RES ili DGK v sostave fosfolipidnykh nanochastits zamedliala okislenie lipidov, indutsirovannoe Cu2+ v bol'sheĭ stepeni v sravnenii so svobodnymi soedineniiami i umen'shala obrazovanie produktov perekisnogo okisleniia (POL). Biodostupnost' RES i DGK pri peroral'nom vvedenii krysam v sostave fosfolipidnykh kompozitsiĭ povyshalas' v 1,5-2 raza. Na modeli ostroĭ gipoksii pri profilakticheskom dvukhnedel'nom vvedenii RES i DGK v sostave fosfolipidnykh kompozitsiĭ bylo pokazano uvelichenie prodolzhitel'nosti zhizni zhivotnykh na 25%, vozrastanie aktivnosti katalazy v gomogenatakh golovnogo mozga v 1,5 raza. Na modeli éndotelial'noĭ disfunktsii u krys, indutsirovannoĭ snizheniem sinteza NO, bylo ustanovleno, chto na fone RES ingibiruiushchee deĭstvie L-NAME – ingibitora sinteza oksida azota – zametno snizhaetsia. Pri étom RES v sostave fosfolipidnykh nanochastits okazyval analogichnoe deĭstvie pri doze v 10 raz men'sheĭ. Nagruzochnaia proba s soprotivleniem (perezhatie voskhodiashcheĭ aorty na 30 s) pokazala, chto fosfolipidnaia kompozitsiia RES okazyvaet bolee éffektivnoe protektornoe deĭstvie za schet stimuliatsii éndotelial'noĭ NOS.
Keywords: bioavailability; dihydroquercetin; endothelial disfunction; hypoxia; phospholipids nanoparticles; resveratrol.