Piperine potentiates the effects of trans-resveratrol on stress-induced depressive-like behavior: involvement of monoaminergic system and cAMP-dependent pathway

Abstract

Stress can act as a precipitation factor in the onset of emotional disorders, particularly depression. Trans-resveratrol is a polyphenolic compound enriched in polygonum cuspidatum and has been found to exert antidepressant-like effects in our previous studies. In present study, we assessed the effects of trans-resveratrol used in combination with piperine, commonly known as a bioavailability enhancer, on chronic unpredictable mild stress-induced depressive-like behaviors and relevant molecular targets. Trans-resveratrol used alone reduced the immobility time of rats in the forced swimming test, with the maximal effects of trans-resveratrol around 60 % inhibition at the highest dose tested, 40 mg/kg. However, when a subthreshold dose of piperine, 2.5 mg/kg was used in combination with trans-resveratrol, the minimum effective dose of trans-resveratrol in reducing the immobility time was reduced to 20 mg/kg. Further evidence from neurochemical (monoamines in the frontal cortex and the hippocampus), biochemical (monoamine oxidase, MAO activities) and molecular biological (cAMP, PKA, CREB and BDNF) assays supported the findings in the behavioral studies. These results suggest that the co-treatment strategy with trans-resveratrol and piperine might be an alternative therapy that provides efficacious protection against chronic stress.

The Antidepressant-like Effect of Flavonoids from Trigonella Foenum-Graecum Seeds in Chronic Restraint Stress Mice via Modulation of Monoamine Regulatory Pathways

“…Depression is characterized by mood disturbances, cognitive functions, anhedonia and attentional deficits [3]. In the modern world, an estimated 17–21% of the population has suffered from depression [4], and rapid social development will increase the risk factors that cause depression.…”

Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats

“… 28 , 29 Additionally, it has been shown that RES treatment can alter the monoaminergic system and the molecular markers related to depression. 30 , 31 However, it remains unknown whether RES can improve depression-like symptoms in CUMS rats, which involve a complicated balance of the HPA axis, the inflammatory reaction, BDNF, and the Wnt/β-catenin pathway.…”

trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis

“…Pharmacokinetic studies demonstrate trans- Resveratrol could be detectable both in plasma and brain, causing both peripheral and central effects (Sale et al, 2004 ; Frozza et al, 2010 ). Our and others' studies have demonstrated that trans- Resveratrol exhibited potential antidepressant and anxiolytic-like effects in various animal models (Damián et al, 2014 ; Ali et al, 2015 ; Ge et al, 2016 ; Xu et al, 2016 ) and increased BDNF protein levels in the hippocampus (Wang et al, 2016c ). Furthermore, trans- Resveratrol was shown to protect intestinal barrier function against oxidative stress (Wang et al, 2016b ).…”