ABSTRACT
BACKGROUND: The development of safe and powerful antidepressant agents from traditional Chinese herbs has become a hotspot in studies on anti-depression therapy. OBJECTIVE: To investigate the anti-depressive effect and possible mechanism of curcumin by behavioral and neurochemical procedures. DESIGN: Randomized grouping design and controlled experiment. SETTING: Depart, ment of Pharmacology, School of Basic Medical Sciences of Peking University.MATERIALS: This study was carried out in the laboratory of the Department of Pharmacology, School of Basic Medical Sciences of Peking University, between November 2003 and October 2004. A total of 240 male ICR mice were recruited. METHODS: The whole experiment was divided into 4 tests. ① Antagonism of reserpine-induced hypothermia: Totally 60 mice were randomly chosen and divided into 6 groups: normal control group, groups of various doses of curcumin (1.25, 2.50, 5.00 and 10.00 mg/kg), and positive control group (imipramine 10 mg/kg). Normal temperature of the mice was measured before experiment. The animals were given a single injection of reserpine (2.5 mg/kg). The mice were administered with drugs 18 hours later, namely, curcumin of different concentrations by gastric perfusion, groundnut oil (0.1 mL/10g by gastric perfusion) as well as imipramine (10 mg/kg by intraperitoneal injection). Rectal temperature was measured 60, 90, 120,150 and 180 minutes after administration, respectively. ② Potentiation of 5-hydroxytryptophan (5-HTP)-induced head twitches: animal grouping was the same as above, and the drug in positive control group was replaced by fluoxetine. The mice received gastric perfusion and the dose of curcumin given was the same as above. Groundnut oil and fluoxetine (10 mg/kg) and 5-HTP (70 mg/kg) were injected into the vein of the tail one hour later.The number of head twitches was counted within 5-10 minutes after 5-HTP treatment. ③ Antagonism of apomorphine-induced hypothermia: Mice grouping was the same as above; the drug in positive control group was replaced by imipramine. Curcumin was give as above at 4 doses, and groundnut oil and imipramine were also given. Large-dose apomorphine was injected subcutaneously (16 mg/kg). Rectal temperature was measured before injection, as well as 30 minutes and 60 minutes after injection. ④Determination of monoamine and metabolites: Mice grouping was the same as above. The drug in positive control group was replaced by imipramine.Curcumin was give as above at 4 doses, and groundnut oil and imipramine were also given. The content of monoamine and metabolites in the mice was measured with high performance liquid chromatography. ⑤ Dunnett's t test was used for comparison between groups.MAIN OUTCOME MEASURES: ① In reserpine-induced hypothermia test, the change of body temperature before and after administration. ② In 5-HTP-induced head twitches test, whether the times of head twitches were increased. ③ In apomorphine-induced hypothermia test, the change of body temperature after administration. ④ Effect of drugs on the content of monoamine.RESULTS: Totally 240 mice entered the result analysis. ① Experiment results of reserpine-induced hypothermia: Curcumin (5 mg/kg and 10 mg/kg)produced an antagonism against reserpine-induced hypothermia, and the results were significantly different from those in control group (P ＜ 0.05,P＜0.01). Curcumin of 10.00 mg/kg produced the similar effect compared as that of imipramine in positive control group. ② Results of 5-HTPinduced head twitches: Curcumin (5 and 10 mg/kg) could significantly increase the times of 5-HTP-induced head twitches (P ＜0.05, P＜0.01). ③Results of apomorphine-induced hypothermia test: 2.50, 5.00 mg/kg and 10.00 mg/kg of curcumin could significantly increase the content of 5-HTP, and 10 mg/kg of curcumin could significantly increase the content of norepinephrine and dopamine. There was significant difference from that in control group (P ＜ 0.05). By contrast, curcumin had no obvious effect on the content of metabolite 5-hydroxyindol acetic acid and 3,4-dihydroxyphenylacetic acid. Imipramine of 10 mg/kg as the positive control drug could significantly increase the content of 5-hydroxyindol acetic acid and norepinephrine (P＜0.05).CONCLUSION: Curcumin has an antidepressant effect and the effect exerted may be related to monoaminergic neurotransmitter system.
ABSTRACT
Objective: To study the effects of melatonin（MT） on inducible nitric oxide synthase (iNOS) expression in hippocampal CA1 at 24 hours and TDT-mediated dUPT nick end labling (TUNEL) positive cells in hippocampal CA1 at 48 hours after global ischemia（20 min）/ reperfusion in rats. Methods: MT was injected intraperitoneally at 0 h, 1 h, 2 h and 6 h after ischemia（20 min） induced by the“occlusion of four arteries”, 2.5 mg*kg－1 or 10 mg*kg－1 each time, respectively. Researching the expression of iNOS in hippocampal CA1 with the immunocytochemistry method 24 hours after reperfusion and the number of TUNEL positive cells in hippocampal CA1 48 hours after reperfusion utilizing TUNEL. Results: At these doses, MT could decrease iNOS expression in hippocampal CA1 at 24 h after global ischemia （20 min）/reperfusion and the number of TUNEL cells in hippocampal CA1 at 48h after reperfusion in rats. Conclusion: Decreasing the expression of deleterious iNOS maybe one of the mechanisms involved in protective action of MT on ischemia-vulnerable brain region.
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Objective To study the preventive role of lysine, proline and calcium ascorbate on experimental osteoporosis in ovariectomized rats. Methods Ninety 6-9-month-old female rats were divided randomly into 9 groups: lysine hydrochloride low dose (LL) and high dose(LH) groups, proline low dose(PL) and high dose(PH) groups, calcium ascorbate low dose(CL) and high dose(CH) groups, calcium gluconate(CG) group, model(MOD) and SHAM groups. All groups except SHAM group were bilaterally ovariectomiged. At the 4 th, 8 th, and 12 th week, blood samples were collected for biochemical examination including the levels of ACP, ALP, Ca and P. Results Compared with SHAM and MOD groups, body weight of LL group increased most. Additionally, LL and LH promoted the activity of ACP and ALP〔(2.250?1.297)U/L and (300.3?136.9)U/L,P
ABSTRACT
The influences of the N -Isosuccinyl - dichloro - cinnamoylamide (7903) on the NA and 5 -HT systems in the brain were studied. Acute administration of 7903 could significantly enhance the level of NA and 5 -HT in mice brain and cortex of rats, and the level of 5 -HT in the hyporthalamus of rats was tending to be enhanced. However, chronic administration of 7903 (two weeks ) could decrease the level of NA and the ra-tio of 5-HIAA/5-HT in the cortex of rats; Chronic administration of 7903 could also decrease the turnover of NA and 5- HT in mice brain, but had no effects on the special binding of ? - receptor to 3-H - DHA and that of 5 -HT receptor to H - ketanserine in the cortex of rats.
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Tetrodotoxin(TTX) is a potent sodium channel blocker. It can affect the generation of action potentials of cell membranes by blocking sodium channel. Damaged tissues express a Tetrodotoxin resistant(TTX R) Na + current which provides a potential target for therapeutic intervention in a range of pain states. We summarize the influence of tetrodotoxin on sodium channel and the possible mechanism of the analgesic effect.
ABSTRACT
The antidepressant effects of the N-Isosuccinyl-dichlorocinnamo-ylamide ( 7903 ) , an analogue of piperine, upon 5 animal models were studied. The 7903 was found to have antidepressant effects on the models with doses less than TD50. The 7903 with the single dose, which did not increase the spontaneous motor activity of animals, could significantly decrease the duration of immobility of mice and rats in the forced-swimming test and that of mice in the tail-suspension test. The duration of the longest permanent immobility indaced by cornea electro-stimulation in mice was also decreased with the chronic administration ( 2 weeks ) of the 7903. And the hypothermia induced by reserpine could be antagonized by the 7903.