Advance in studies on natural antidepressant drugs and cytochrome P450 / 中国中药杂志

In the fast pace of modern life and under the heavy work pressure, the prevalence of depression has increased year by year. Meanwhile, the demands for antidepressant drugs have also grown, especially the high-efficiency and low-toxicity natural antidepressant drugs, mainly including polyphenols, flavonoids, organic acids, alkaloids and terpenoids. Cytochrome P450 (CYP450) is a type of enzymes involving oxidative metabolism of drugs in vivo, and can change the pharmacokinetics and efficacy of drugs. Therefore, it is of important significant to define the effect of natural antidepressant drugs on CYP450 in human bodies, in order to improve the rational clinical medication, avoid drug interactions and reduce adverse reactions.

Effect of fluoxetine on the expressions of BDNF and Bcl-2 during fear memory formation / 药学学报

The aim of this study is to investigate the effect of fluoxetine (FLX) on the expressions of BDNF and Bcl-2 in the hippocampus, the amygdala and the prefrontal cortex of conditioned fear (CF) model mice. Forty eight mice were randomly divided into three groups, normal control group, CF stress group and FLX-pretreated CF group. The FLX-pretreated CF group was given FLX (10 mg x kg(-1) x d(-1)) for 7 days before CF stress. After CF stress model was established, all mice were given behavioral experiments to test whether FLX impaired or improved the auditory and contextual fear conditioning. Then mice were sacrificed. The expressions of BDNF and Bcl-2 were detected by Western blotting. The results showed that the freezing time of FLX-pretreated CF group was significantly lower than that of CF group; FLX pretreatment up-regulated the expression of Bcl-2 in the hippocampus at 1 d after CF stress (P < 0.001), but no significant differences was observed at 7 d; BDNF significantly increased in the hippocampus at 7 d (P < 0.001), but no differences at 1 d; the expressions of BDNF and Bcl-2 in the amygdala and the prefrontal cortex were of no obvious differences between CF group and FLX-pretreated CF group at 1 d or 7 d after CF stress. Parallel to these changes, pretreatment with FLX could affect histopathologic changes induced by CF stress. Furthermore, the results indicated that FLX pretreatment could protect against CF stress-induced neurological damage via the activation of BDNF and Bcl-2 in hippocampus.

Analgesic effect of ferulic acid on CCI mice: behavior and neurobiological analysis / 中国中药杂志

To study the analgesic effect of chronic administration with ferulic acid, and preliminarily discuss its mechanism. Thermal hyperalgesia and mechanical allodynia tests were conducted to observe the analgesic effect of chronic administration with ferulic acid on CCI mice. The neurochemical detection method was applied to observe the effect chronic administration with ferulic acid on monoamine neurotransmitter and monoamine oxidase activity. Compared with the normal group, CCI mice showed notable reduction in heat sensation and nociceptive threshold in and mechanical allodynia. Ferulic acid (10, 20, 40 and 80 mg x kg(-1), po) could significantly reverse the situations. In an in-depth study, we found that the reason for these results was that ferulic acid was dose-dependent in increasing 5-HT and NE levels in hippocampus, frontal cortex and amygdale and could inhibit MAO-A activity in mouse brains. These results showed that ferulic acid has the analgesic effect. Its mechanism may be related to the inhibition of monoamine oxidase activity and the increase in monoamine neurotransmitter in mouse brains.

Effect of piperine on 5-HT and synaptophysin expression of rats with irritable bowel syndrome / 药学学报

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.

Effect of curcumin on 5-hydroxytryptamine and brain-derived neurotrophic factor in irritable bowel syndrome rats / 中华神经医学杂志

Objective To investigate the pathogenesis of irritable bowel syndrome (IBS) from the aspect of brain-gut interaction and find out the efficacy and mechanism of curcumin on IBS.Methods Forty-eight rats were chosen in our study,and divided into 6 groups (n=8):normal group,IBS model group,IBS+curcumin treatment groups (10,20 and 40 mg/kg of curcumin via intragastric administration 1 h before model inducement) and IBS+imipramine treatment group (10 mg/kg,via intraperitoneal injection 30 min before model inducement); IBS rat models were established by chronic and acute stress; treatments in each group were given for a consecutive 21 days.The depression-like behaviors and gut hypersensitivity of the rats in all the groups were detected.The expressions of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in the cerebral cortex and ileum were determined by high performance liquid chromatography (HPLC) and Western blotting,respectively.Results The sucrose consumption of IBS rat had been significantly reduced and the intestinal viscera sensitivity was obviously elevated in the IBS model group as compared with those in the normal group (P＜0.05); as compared with those in the normal control group,the expression of 5-HT significantly decreased inthe cerebral cortex of IBS modelgroup (P＜0.05),but opposite presentations were noted in the ileum (P＜0.05).As compared with that in the normal group,the BDNF expression in the brain frontal cortex was significantly decreased but obviously increased in the ileum (P＜0.05).High doses of curcumin (40 mg/kg treatment groups) improved the behavior ofIBS rats,and reversed the levels of 5-HT in the cerebral cortex and ileum,with significant difference (P＜0.05); besides,they could significantly reverse the BDNF level in the cerebral cortex and ileum,with significant difference (P＜0.05).Conclusion IBS rat models have abnormal expressions of 5-HT and 5-HIAA,and BDNF in the brain-gut system,which indicates that alterations of brain-gut exist during IBS; curcumin can improve the behavior changes and regulate the expression of serotonin and BDNF in IBS rats.

Influence of ferulic acid on the pain-depression dyad induced by reserpine / 药学学报

This study is to offer a clinical pain-depression dyad therapy of ferulic acid, the pain-depression dyad induced by reserpine was established and the dose-effect relationship of ferulic acid on ameliorating pain-depression dyad was explored. Mice were randomly divided into control group, reserpine + vechile and reserpine + ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)) groups. The reserpine treated mice were tested with thermal hyperalgesia, mechanicial allodynia and forced swimming tests, and the SOD and NO levels of hippocampus and frontal cortex were measured. Moreover, the HPLC-ECD was used to detect the changes of central monoamines concentrations. Compared with control group, reserpine can induce a significant decrease in the nociceptive threshold and increase in the immobility time of the forced swimming test. The results suggested that reserpine significantly increased the level of nitrite in hippocampus and frontal cortex and reduced the levels of SOD, 5-HT and NE in these two brain regions. However, these indexes can be a dose-dependently reversed by ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)). Ferulic acid can reverse pain-depression dyad, especially at the dose of 80 mg x kg(-1). In addition, it can influence oxidative stress and monoamine level.

Effects of kindling epilepsy and low frequency of epileptic focus on spontaneous neuropathic pain in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of epileptogenesis and low frequency stimulation at epileptic focus on spontaneous neuropathic pain in rats.</p><p><b>METHODS</b>Bipolar stimulating electrodes were implanted in the amygdala and current with constant intensity was applied to evoke kindling-induced seizures. In partial and generalized stages of seizure acquisition, neuroma model of spontaneous neuropathic pain was prepared by completely transection of the left sciatic and saphenous nerves of rats. Autotomy behavior was scored daily until d 63 postoperatively. Rats were divided into 5 groups: Control (n=7), rats with partial seizures (1-3 stages, n=5), rats with generalized seizures (4-5 stages, n=7), rats with partial seizures and low frequency stimulation(n=4), rats with generalized seizures and low frequency stimulation(n=4). Low frequency stimulation was applied to the amygdala, the epileptic focus for 21 d from the d 2 after nerve transection.</p><p><b>RESULTS</b>Autotomy level in rats with partial seizures was significantly lower than that in controls. The autotomy scores during postoperative d 40 ≊63 were significantly lower than those of controls, the area under the progression curve of autotomy behavior was decreased from 308.2 ±51.57 to 45.80 ±24.64, the onset day of autotomy was postponed by 32 d and none of the animals with partial seizures showed high autotomy, while 71.4 % of controls showed that on d 63 postoperatively. Rats with generalized seizures showed autotomy similar to controls, except that the onset day was postponed by 16 d. Autotomy behavior in rats receiving low frequency stimulation of the amygdala was not different from that in controls.</p><p><b>CONCLUSION</b>Focal seizures can lower sensitivity to spontaneous neuropathic pain in rats, while low frequency stimulation applied to the focus can abolish such effect.</p>

Antidepressant effect of acute administration with Jianyate Hao (JYTH) and its possible mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>