ABSTRACT
The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects.
Subject(s)
Alkaloids/pharmacology , Antidepressive Agents/pharmacology , Benzodioxoles/pharmacology , Biogenic Monoamines/metabolism , Coumaric Acids/pharmacology , Neurotransmitter Agents/metabolism , Piperidines/pharmacology , Polyunsaturated Alkamides/pharmacology , Animals , Biological Availability , Brain Chemistry/drug effects , Depression/drug therapy , Depression/metabolism , Drug Synergism , Hindlimb Suspension/psychology , Male , Mice , Mice, Inbred ICR , Monoamine Oxidase/metabolism , Motor Activity/drug effects , Swimming/psychologyABSTRACT
Irritable bowel syndrome (IBS) is induced by dysfunction of central nervous and peripheral intestinal systems, which affects an estimated 10-15% population worldwide annually. Stress-related psychiatric disorders including depression and anxiety are often comorbid with gastrointestinal function disorder, such as IBS. However, the mechanism of IBS still remains unknown. Curcumin is a biologically active phytochemical presents in turmeric and has pharmacological actions that benefit patients with depression and anxiety. Our study found that IBS rats showed depression- and anxiety-like behaviors associated with decreased 5-HT (serotonin), BDNF (Brain-derived neurotrophic factor) and pCREB (phosphorylation of cAMP response element-binding protein) expression in the hippocampus after chronic acute combining stress (CAS). However, these decreased parameters were obviously increased in the colonic after CAS. Curcumin (40 mg/kg) reduced the immobility time of forced swimming and the number of buried marbles in behavioral tests of CAS rats. Curcumin also decreased the number of fecal output and abdominal withdrawal reflex (AWR) scores in response to graded distention. Moreover, curcumin increased serotonin, BDNF and pCREB levels in the hippocampus, but they were decreased in the colonic of CAS rats. 5-HT(1A) receptor antagonist NAN-190 reversed the effects of curcumin on behaviors and the changes of intestine, pCREB and BDNF expression, which are related to IBS. These results suggested that curcumin exerts the effects on IBS through regulating neurotransmitters, BDNF and CREB signaling both in the brain and peripheral intestinal system.
Subject(s)
Curcumin/therapeutic use , Enteric Nervous System/physiopathology , Hippocampus/physiopathology , Irritable Bowel Syndrome/drug therapy , Serotonin/physiology , Animals , Anxiety/drug therapy , Anxiety/physiopathology , Brain-Derived Neurotrophic Factor/biosynthesis , Colon/metabolism , Curcumin/pharmacology , Cyclic AMP Response Element-Binding Protein/biosynthesis , Defecation , Diazepam/pharmacology , Disease Models, Animal , Drug Evaluation, Preclinical , Gastrointestinal Motility/drug effects , Hippocampus/metabolism , Imipramine/pharmacology , Irritable Bowel Syndrome/physiopathology , Male , Phosphorylation , Physical Exertion , Piperazines/pharmacology , Pressure/adverse effects , Protein Processing, Post-Translational , Rats , Rats, Sprague-Dawley , Receptor, Serotonin, 5-HT1A/biosynthesis , Receptor, Serotonin, 5-HT1A/drug effects , Receptor, Serotonin, 5-HT1A/physiology , Serotonin/biosynthesis , Serotonin 5-HT1 Receptor Antagonists/pharmacology , Signal Transduction , Stress, Physiological/physiology , Stress, Psychological/physiopathology , Up-Regulation/drug effectsABSTRACT
This study is to explore the amelioration of piperine on chronic acute combining stress rat with depression-like behavior, visceral sensitivity, and its effect on the expression of serotonin (5-HT) and synaptophysin. Forty two SD rats were divided into seven groups: blank group, model group, piperine (12.5, 25, 50 and 100 mgkg-1, ig) and imipramine (10 mgkg-1, ip) groups. The rat model of irritable bowel syndrome was established by chronic acute combining stress, and then to evaluate depression-like behavior and visceral sensitivity. The expressions of 5-HT and synaptophysin in the hippocampus and colon were determined by high performance liquid chromatography (HPLC) and Western blotting, respectively. The duration of immobility of IBS rat in the forced swimming test had been significantly increased, the sucrose consumption of IBS rat had been reduced and visceral sensitivity was obviously elevated in the IBS model group as compared with those in the normal control group (P<0.05, P<0.01). As compared with those in the normal control group, the expression of 5-HT significantly decreased, 5-HIAA/5-HT ratio significantly increased in the hippocampus of IBS model group (P<0.05), but opposite presentations were noted in the colon (P<0.05). As compared with that in the normal control group, the synaptophysin expression in the hippocampus decreased significantly but obviously increased in the colon (P<0.05). Piperine improved the behavior of IBS rats, and reversed the levels of 5-HT and 5-HIAA, and 5-HIAA/5-HT proportion in the hippocampus and colon (P<0.05); besides, they significantly reverse the synaptophysin level in the hippocampus and colon (P<0.05). The presence of depression and visceral sensitivity had been changed in IBS rats, with abnormal expression of 5-HT and synaptophysin in the brain-gut system. Piperine can ameliorate the changes of the behavior and regulation of serotonin and synaptophysin expression in IBS rat model.
Subject(s)
Alkaloids/pharmacology , Benzodioxoles/pharmacology , Irritable Bowel Syndrome/metabolism , Piperidines/pharmacology , Polyunsaturated Alkamides/pharmacology , Serotonin/metabolism , Synaptophysin/metabolism , Alkaloids/isolation & purification , Animals , Benzodioxoles/isolation & purification , Colon/metabolism , Hippocampus/metabolism , Hydroxyindoleacetic Acid/metabolism , Irritable Bowel Syndrome/physiopathology , Male , Motor Activity/drug effects , Piper nigrum/chemistry , Piperidines/isolation & purification , Plants, Medicinal/chemistry , Polyunsaturated Alkamides/isolation & purification , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: Jianyate Hao (JYTH) , a traditional Chinese medicine formula, which has been used effectively to treat depression in the past ten years. The purpose of this study was to explore the antidepressant effect of acute administration with JYTH and its possible mechanism. METHOD: the animals behavioral despair models of depression, the tail suspension and forced swimming tests, were used to explore the antidepressant effects of JYTH. In addition, the locomotor activity test was used to detect the change of locomotor activity. The monoamine oxidase activity in the mouse brain was also determined by using fluorospectrophotometry. RESULT: JYTH (17.5, 35, 70 g x kg(-1), ig) could decrease the duration of immobility in both tail suspension and forced swimming tests, and the effect of JYTH (35 g x kg(-1) ig) was resembling imipramine (10 mg x kg(-1), ip) in relieving depression. And the effective doses (17.5, 35, 70 g x kg(-1), ig) did not alter locomotion activity. Moreover, JYTH (35 g x kg(-1), ig) was found to inhibit monoamine oxidase activity in the mouse brain. CONCLUSION: These findings suggest that JYTH exerts antidepressant effect in animals behavioral despair tests and the underlying mechamism may involve the inhibition monoamine oxidase activity in the mouse brain.
