Piperine potentiates the antidepressant-like effect of trans-resveratrol: involvement of monoaminergic system
Piperine potentiates the antidepressant-like effect of trans-resveratrol: involvement of monoaminergic system
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DOI：
10.1007/s11011-013-9426-y
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发表时间：
2013-12-01
影响因子：
3.6
通讯作者：
Pan, Jianchun
中科院分区：
文献类型：
--
作者：
Huang, Wu;Chen, Zhuoyou;Pan, Jianchun
重度抑郁症的特点是神经内分泌和免疫网络功能障碍。反式白藜芦醇是虎杖中存在的一种酚类化合物，此前已被证明可通过调节单胺能系统、氧化/抗氧化防御和炎症反应发挥抗抑郁样作用。本研究研究了反式白藜芦醇和生物利用度增强剂胡椒碱在小鼠体内的协同抗抑郁样作用，并探讨了可能的机制。在尾部悬挂和强迫游泳测试（TST 和 FST）中，反式白藜芦醇被证明可以减少不动时间。但即使剂量增加160 mg/kg，最大抑制率也接近60%；而胡椒碱在这两个模型中产生了微弱的抗抑郁样作用。等辐射线分析证明，反式白藜芦醇和胡椒碱之间的相互作用显示出明显的协同效应。进一步的研究表明，在 TST 和 FST 中用对氯苯丙氨酸（PCPA，300 mg/kg，腹腔注射）预处理可以消除阈下剂量的胡椒碱（2.5 mg/kg）和低剂量反式白藜芦醇（10 和 20 mg/kg）的抗不动反应，表明血清素能系统的参与。此外，用阈下剂量的胡椒碱和低剂量的反式白藜芦醇治疗可减轻利血平引起的体温过低和上睑下垂，这与去甲肾上腺素的相关性有关。来自神经化学（额叶皮质、海马和下丘脑中的单胺）和生物化学（单胺氧化酶、MAO 活性）测定的额外证据证实了反式白藜芦醇和胡椒碱联合治疗后单胺能系统的协同升高。目前的结果表明，反式白藜芦醇与胡椒碱联合对抑郁样行为的影响可能部分归因于大脑中单胺能系统的增强激活。需要进一步的研究来阐明氧化/亚硝化应激、炎症和神经保护途径在该组合的抗抑郁样作用中的作用。组合所获得的协同效应可能为设计高效、低副作用的新型抗抑郁药物提供创新线索。
Major depression is characterized by dysfunction of neuroendocrine and immune networks. Trans-resveratrol, a phenolic compound presented in polygonum cuspidatum, was demonstrated previously to exert antidepressant-like effects through regulating monoaminergic system, oxidative/antioxidant defense and inflammatory response. The present study investigated the synergistic antidepressant-like effect of trans-resveratrol and piperine, a bioavailability enhancer, in mice and explored the possible mechanism. Trans-resveratrol was shown to reduce the immobility time both in the tail suspension and forced swimming tests (TST and FST). But the maximal inhibition was nearly 60 % even if the doses were increased by 160 mg/kg; while piperine produced weak antidepressant-like effects in these two models. The interaction between trans-resveratrol and piperine was shown a clear-cut synergistic effect as evidenced by an isobolographic analysis. The further study suggested that the anti-immobility response from the subthreshold dose of piperine (2.5 mg/kg) and low doses of trans-resveratrol (10 and 20 mg/kg) was abolished by pretreatment with para-chlorophenylalanine (PCPA, 300 mg/kg, i.p.) in TST and FST, indicating the involvement of serotonergic system. Moreover, treatment with the subthreshold dose of piperine and low doses of trans-resveratrol attenuated reserpine-induced hypothermia and ptosis arguing for the relevance of noradrenaline. Additional evidence from neurochemical (monoamines in the frontal cortex, hippocampus, and hypothalamus) and biochemical (monoamine oxidase, MAO activity) assays corroborated the synergistically elevated monoaminergic system after co-treatment with trans-resveratrol and piperine. The present results indicate the effect of trans-resveratrol combined with piperine on depressive-like behaviors may be partly due to the potentiated activation of monoaminergic system in the brain. Further studies are necessary to elucidate the involvement of the oxidative/nitrosative stress, inflammatory and neuroprotective pathway in the antidepressant-like effect of this combination. The synergistic effect obtained from the combination may provide innovative clues for designing novel antidepressants with high efficacy and low side effects.