Inhibitory effects of cis- and trans-resveratrol on noradrenaline and 5-hydroxytryptamine uptake and on monoamine oxidase activity.
This study investigated for the first time the potential effects of cis- and trans-resveratrol (c-RESV and t-RESV) on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake by synaptosomes from rat brain, on 5-HT uptake by human platelets, and on monoamine oxidase (MAO) isoform activity. Both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the uptake of [3H]NA and [3H]5-HT by synaptosomes from rat brain and the uptake of [3H]5-HT by human platelets. In both experimental models, t-RESV was slightly more efficient than c-RESV. Furthermore, in synaptosomes from rat brain, the RESV isomers were less selective against [3H]5-HT uptake than the reference drug fluoxetine (0.1-30 microM). On the other hand, both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the enzymatic activity of commercial (human recombinant) MAO isoform (MAO-A and MAO-B) activity, c-RESV being slightly less effective than t-RESV. In addition, both RESV isomers were slight but significantly more selective against MAO-A than against MAO-B. Since the principal groups of drugs used in the treatment of depressive disorders are NA/5-HT uptake or MAO inhibitors, under the assumption that the RESV isomers exhibit a similar behaviour in humans in vivo, our results suggest that these natural polyphenols may be of value as structural templates for the design and development of new antidepressant drugs with two important biochemical activities combined in the same chemical structure: NA/5-HT uptake and MAO inhibitory activity.
Yáñez
Matilde
M
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela (La Coruña), Spain.
Fraiz
Nuria
N
Cano
Ernesto
E
Orallo
Francisco
F
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007536:Isomerism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008995:Monoamine Oxidase / Q000378:metabolism*; D009638:Norepinephrine / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012701:Serotonin / Q000493:pharmacokinetics*; D013267:Stilbenes / Q000008:administration & dosage* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D013267:Stilbenes; D012701:Serotonin; D008995:Monoamine Oxidase; D000077185:Resveratrol; D009638:Norepinephrine