J. Crayton Pruitt Family Department of Biomedical Engineering and Evelyn F. & William L. Mcknight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
Pharmacol Biochem Behav. 2010 Jan;94(3):447-53. doi: 10.1016/j.pbb.2009.10.007. Epub 2009 Oct 23.
Proanthocyanidin is a phenolic product present in plants which has antioxidant, antinociceptive and neuroprotective properties, without inducing significant toxicological effects. The present study tested the hypothesis that low molecular proanthocyanidin from grapes that has optimized bioavailability, would exert antidepressant-like activities in behavioral despair tests. The results suggested that oral administration proanthocyanidin at doses of 25 and 50mg/kg for 7days significantly reduced the duration of immobility in both the tail suspension and forced swimming tests. The doses that affected the immobile response did not affect locomotor activity. In addition, the neurochemical and neuropharmacological assays showed that proanthocyanidin produced a marked increase of 5-HT levels at 25 and 50mg/kg in three brain regions, the frontal cortex, hippocampus and hypothalamus. Noradrenaline and dopamine levels were also increased when higher dose of proanthocyanidin (50mg/kg) administration both in the frontal cortex and hippocampus. These effects were similar to those observed for the classical antidepressant imipramine (10mg/kg, i.p.). Moreover, Our study suggested that proanthocyanidin (12.5, 25 and 50mg/kg) dose dependently inhibited monoamine oxidase-A (MAO-A) activity, while MAO-B inhibitory activity was also found at higher doses (25 and 50mg/kg) after 7days administration. MAO-A selective inhibitor, moclobemide (20mg/kg, i.g.) produced MAO-A inhibition of 70.5% in the mouse brain. These findings suggest that the antidepressant-like effects of proanthocyanidin may involve the central monoaminergic neurotransmitter systems.
原花青素是一种存在于植物中的酚类产物，具有抗氧化、抗伤害感受和神经保护作用，而不会引起明显的毒理学效应。本研究检验了这样一个假设，即具有优化生物利用度的低分子葡萄籽原花青素，会在行为绝望试验中表现出抗抑郁样活性。结果表明，连续 7 天口服 25 和 50mg/kg 的原花青素可显著缩短悬尾和强迫游泳试验中不动时间。影响不动反应的剂量不影响运动活性。此外，神经化学和神经药理学测定表明，原花青素在三个脑区（额叶皮层、海马和下丘脑）以 25 和 50mg/kg 的剂量产生了 5-HT 水平的显著增加。当给予较高剂量的原花青素（50mg/kg）时，去甲肾上腺素和多巴胺水平在前额叶皮层和海马中也增加。这些作用与经典抗抑郁药丙咪嗪（10mg/kg，ip）相似。此外，我们的研究表明，原花青素（12.5、25 和 50mg/kg）剂量依赖性地抑制单胺氧化酶-A（MAO-A）活性，而在 7 天给药后较高剂量（25 和 50mg/kg）也发现 MAO-B 抑制活性。MAO-A 选择性抑制剂吗氯贝胺（20mg/kg，ig）在小鼠脑中产生了 70.5%的 MAO-A 抑制。这些发现表明，原花青素的抗抑郁样作用可能涉及中枢单胺能神经递质系统。
