Although the number of prescriptions and dependence on sleeping pills are increasing, the associations with unexpected abnormal behaviors and metabolic diseases caused by the overuse of sleeping pills are not well understood. In particular, such as abnormal eating-behavior and the occurrence of metabolic disorders caused by psychological unstable states are reported. For this reason, herbal medicine, which has not had such side effects in recent years, is attracting attention as an alternative medicine/food for sleeping inducer. We have used ethanol extracts from Passiflora incarnata (PI) to steadily obtain positive effects on sleep and brain microenvironment. However, as mentioned earlier, sleep-inducing efficacy can only be used safely if the behavioral and metabolic abnormalities do not appear.Thus, in this study, we used Phenomaster equipment to continuously monitor the movement, feeding, water consumption, gas changes, etc. in C57BL/6 mice at a dose of 500 mg/kg/day for 5 consecutive days with PI extract group compared with the control group. Before sacrifice, differences in body composition of mice were also compared. Monitoring of 24 h/5 days through the equipment showed no change in PI-treated group in anything except for significant decrease in blood melatonin levels and activity after PI administration. Taken together, the statistically insignificance of any behavioral and metabolic phenomenon produced by repeated treatment of PI are not only expected to have an accurate sleep effect, but are also free of side effects of the prescribed sleeping pills. This study has given us greater confidence in the safety of the PI extracts we use for sleep-inducer.
Administration, Oral ; Animals ; Body Composition ; Brain ; Drinking ; Ethanol ; Herbal Medicine ; Melatonin ; Metabolic Diseases ; Metabolic Phenomena ; Mice ; Passiflora ; Prescriptions ; Sleep Initiation and Maintenance Disorders

OBJECTIVETo observe the seasonal changes in serum levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and melatonin (MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis.

METHODSOne hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer (n=80) and winter (n=80) respectively: normal group, collagen-induced arthritis (CIA) model group, operation group, and sham-operation group (n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was. The serum levels of IL-1β, IL-6 and MT in different groups were measured by radioimmunoassay.

RESULTSCompared with the normal group, the serum levels of IL-1β and IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter (IL-1β in summer, P=0.008, P<0.01, P=0.012; IL-1β in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024; IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1β and IL-6 in winter were higher than in summer, but with no statistically significant differences (P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group (P=0.002, 0.008) and the sham-operation group (P=0.003, 0.007), while significantly decreased in the operation group (P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter (P=0.947).

CONCLUSIONSThe increase of serum levels of IL-1β and IL-6 may exacerbate the inflammatory reaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1β, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.

Animals ; Arthritis, Experimental ; blood ; Collagen ; administration & dosage ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Kidney Diseases ; blood ; Melatonin ; blood ; Rats ; Rats, Sprague-Dawley ; Seasons

OBJECTIVETo explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months.

METHODSExperiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric gavage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo.

RESULTSLow dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead.

CONCLUSIONMelatonin is not suitable for normal and lead-exposed children.

Animals ; Female ; Lead ; toxicity ; Learning ; drug effects ; Long-Term Potentiation ; drug effects ; Male ; Maze Learning ; drug effects ; Melatonin ; administration & dosage ; toxicity ; Rats ; Spatial Behavior ; drug effects

PURPOSE: Melatonin, the most potent scavenger of toxic free radicals, has been found to be effective in protecting against pathological states due to the release of reactive oxygen species. This study was performed to establish the effect of high dose melatonin on protection against ischemia- reperfusion (I/R) injury in rat hearts. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were used in this study. They were separated into four groups of ten rats each. A left coronary artery occlusion was induced in the rats by ligating the artery for 20 minutes and then releasing the ligation (reperfusion) afterwards. The control group was Group A. Group B was subjected to myocardial ischemia-reperfusion without any treatment, while Group C underwent myocardial ischemia-reperfusion with a melatonin treatment before the ischemia. Group D was subjected to myocardial ischemia-reperfusion with a melatonin treatment before the reperfusion. After 20 minutes of reperfusion, blood samples were obtained from each group for biochemical studies, and the animals were sacrificed for histological and, immunohistochemical examinations of the myocardial tissue. RESULTS: We found that the cardiac troponin T(cTn-T) levels were significantly increased in Group B when all groups were compared. In the Group C rats treated with melatonin, the cTn-T values were significantly lower than those in Groups B and D. In addition, malondialdehyde (MDA) and antioxidant enzymes including, superoxide dismutase (SOD) and myeloperoxidase (MPO) were lower than those in Group B in the melatonin treated groups. The differences were statistically significant (p < 0.05). Histopathologic and immunohistopathologic studies also supported the effectiveness of melatonin. CONCLUSION: Our study suggests that high dose melatonin, appears to offer protection against cardiac ischemia-reperfusion injuries in rats by scavenging the free radicals and could have a potential clinical use in the management of myocardial ischemia.
Animals ; Antioxidants/administration & dosage/*therapeutic use ; Male ; Malondialdehyde/metabolism ; Melatonin/administration & dosage/*therapeutic use ; Myocardial Reperfusion Injury/*drug therapy/pathology ; Peroxidase/metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase/metabolism ; Troponin/metabolism

OBJECTIVETo study whether Danggui Shaoyao Powder (DSP) is by way of improving pineal function to realize its anti-aging effects.

METHODSForty aged rats were randomly divided into the sham operated group (A), the pinealectomized group (B), the sham medicated group (C), the pinealectomized and medicated group (D). The medication given was gastric perfusion of DSP for 3 weeks. Learning and memory ability of rats was observed using Morris water maze and the serum melatonin (MLT) concentration of the rats was measured by radio-immunoassay.

RESULTSThe average escape latency in Group B was significantly longer than that in other groups (P <0.05). The times of passing through the platform and the percentage of swimming distance in Group C were significantly higher than those in other groups (P <0.05). The serum MLT was higher at daytime than at night in Group C and D (P <0.05); that at daytime in Group C was higher than Group A (P <0.05) and also higher in Group D than Group B; that at daytime was higher in Group C than Group D; that at night markedly decreased in Group D as compared with Group B (P <0.05).

CONCLUSIONDSP could increase the melatonin secretion and improve learning and memory ability. Since its effects reduced after pinealectomy, it could be deduced that improving pineal function should be one of the action mechanisms for anti-aging.

Aging ; drug effects ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Learning ; drug effects ; Melatonin ; blood ; Memory ; drug effects ; Pineal Gland ; drug effects ; secretion ; Powders ; Rats

PURPOSE: We evaluated the protective effects of cranberry, which is known as a fruit with anti-oxidative effects, on infection-induced oxidative renal damage with using a rabbit vesico-ureteral reflux (VUR) model. MATERIALS AND METHODS: New Zealand male rabbits were divided into 5 groups (the control group, VUR group, E. coli group, cranberry group and melatonin group). VUR was created and confirmed at 2 weeks after the operation. Infection was induced by intravesical instillation of an E. coli suspension. Cranberry powder was supplied with the feed. Melatonin was injected into the peritoneal cavity. The rabbit kidneys were obtained 3 weeks after the operation. Histopathologic examination was performed to evaluate for inflammation, fibrosis and the tubular change. The oxidative renal damage was evaluated by measuring malondialdehyde (MDA) in the renal tissue. RESULTS: Grossly, the refluxing kidney was larger than the contralateral normal kidney and the refluxing ureter was dilated and tortuous. The microscopic observation of the kidneys from the E. coli group showed apparent periglomerular mononuclear cell infiltration, tubular dilatation and atrophy, and interstitial fibrosis. The kidneys from the reflux group, cranberry group and melatonin group showed mild mononuclear cell infiltration without interstitial fibrosis. The MDA level in the kidneys of the E. coli group was significantly higher than that in the control, cranberry and melatonin groups (p<0.05). The MDA level in the cranberry and melatonin groups didn't significantly differ from that in the sterile group. CONCLUSIONS: This study demonstrates that cranberry has an anti-inflammatory effect due to an anti-oxidative function and it may prevent infection-induced oxidative renal damage. But application of cranberry in children with VUR needs more clinical studies.
Administration, Intravesical ; Atrophy ; Child ; Dilatation ; Fibrosis ; Fruit ; Humans ; Inflammation ; Kidney ; Male ; Malondialdehyde ; Melatonin ; New Zealand ; Peritoneal Cavity ; Rabbits ; Reactive Oxygen Species ; Ureter ; Vaccinium macrocarpon* ; Vesico-Ureteral Reflux*

OBJECTIVETo investigate the effect of amino acid parenteral nutritional (PN) support on serum tryptophan and melatonin in non-small cell lung cancer (NSCLC) patients receiving chemotherapy.

METHODSSeventy-two patients with inoperable NSCLC were divided into three groups randomly: control group, 250 ml/d amino acids PN therapy group and 500 ml/d amino acids PN therapy group. The same NP (cisplatin + vinorelbine) chemotherapy was carried out in all the three groups. During three sessions of chemotherapy,amino acids PN therapy was given to the amino acids PN therapy groups. Serum tryptophan and melatonin concentration changes were assessed before and after chemotherapy.

RESULTSAfter chemotherapy the concentration of MT and Try were much lower than that before chemotherapy in the three group patients (P < 0.05). But the concentration of MT and Try in the PN group patients was higher than that in control group patients. The concentration of MT and Try in the 500 ml/d amino acid parenteral nutritional support group patients were significantly higher than that in the 250 ml/d group patients, the difference was significant (P < 0.05).

CONCLUSIONAmino acid parenteral nutritional support is beneficial to improve the lower concentration of serum MT and Try in NSCLC patients receiving chemotherapy, and a more significant effect can be achieved by the 500 ml/d amino acid parenteral nutritional support treatment.

Aged ; Amino Acids ; administration & dosage ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; therapy ; Cisplatin ; administration & dosage ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; therapy ; Male ; Melatonin ; blood ; Neoplasm Staging ; Parenteral Nutrition ; Treatment Outcome ; Tryptophan ; blood ; Vinblastine ; administration & dosage ; analogs & derivatives

Animals ; Animals, Newborn ; Antioxidants ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Brain ; drug effects ; pathology ; Disease Models, Animal ; Female ; Hypoxia-Ischemia, Brain ; drug therapy ; metabolism ; pathology ; Immunohistochemistry ; Male ; Melatonin ; administration & dosage ; pharmacology ; Neuroprotective Agents ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate effect of inhibiting melatonin biosynthesis on activities of protein kinase A (PKA), glycogen synthase kinase-3 (GSK-3) and tau phosphorylation at PS214 and M4 epitopes using haloperidol, a specific inhibitor of 5-hydroxyindole-O-methyltransferase.

METHODSBrain ventricular and intraperitoneal injections were used for haloperidol administration, Western blots for tau phosphorylation, 32P-labeling for PKA and GSK-3 activity, and high performance liquid chromatograph for detection of serum melatonin levels.

RESULTSHaloperidol injection through the lateral ventricle and intraperitoneal reinforcement significantly stimulated PKA activity with a concurrent hyperphosphorylation of tau at M4 (Thr231/Ser235) and PS214 (Ser214) sites. Prior treatment of the rats using melatonin supplement for one week and reinforcement during the haloperidol administration arrested PKA activity and attenuated tau hyperphosphorylation. GSK-3 activity showed no obvious change after haloperidol injection, however, melatonin supplements and reinforcements during haloperidol infusion inactivated basal activity of GSK-3.

CONCLUSIONDecreased melatonin may be involved in Alzheimer-like tau hyperphosphorylation, and overactivation of PKA may play a crucial role in this process.

Animals ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Epitopes ; Glycogen Synthase Kinase 3 ; metabolism ; Haloperidol ; administration & dosage ; pharmacology ; Hippocampus ; enzymology ; metabolism ; Injections, Intraperitoneal ; Injections, Intraventricular ; Male ; Melatonin ; biosynthesis ; blood ; Phosphorylation ; drug effects ; Rats ; Rats, Wistar ; tau Proteins ; metabolism

Hyperphosphorylated microtubule-associated protein tau is the major protein component of neurofibrillary tangles in the brain of patients with Alzheimer's disease (AD). Until now, there is no effective cure to arrest this hyperphosphorylation. The present study was designed to explore the in vivo preventive effect of melatonin on Alzheimer-like tau hyperphosphorylation. Isoproterenol, a beta-receptor agonist, was used to induce tau hyperphosphorylation, and for preventive effect of melatonin, the rats were injected intraperitoneally with melatonin for 5 d before hippocampi infusion of isoproterenol. The level of tau phosphorylation was detected by Western blot and immunohistochemistry using sites specific antibodies (PHF-1 and Tau-1), and it was normalized by non-phosphorylation dependent total tau antibody (111e). The results by Western blot showed that the immunoreaction of tau at PHF-1 epitope was enhanced, and the reaction at Tau-1 epitope was weakened significantly at 48 h after injection of isoproterenol, suggesting hyperphosphorylation of tau at Ser 396/Ser 404 (PHF-1) and Ser199/Ser 202 (Tau-1) sites. Similar results were observed by immunohistochemistry staining, in which hyperphosphorylated tau was mainly detected in mossy fibers of hippocampal CA3 region. Pre-injection of rats with melatonin intraperitoneally arrested effectively the isoproterenol-induced tau hyperphosphorylation at both Tau-1 and PHF-1 sites, implying the preventive effect of melatonin in Alzheimer-like tau hyperphosphorylation.
Alzheimer Disease ; metabolism ; Animals ; Brain ; metabolism ; Isoproterenol ; administration & dosage ; antagonists & inhibitors ; Male ; Melatonin ; pharmacology ; Neurofibrillary Tangles ; drug effects ; metabolism ; Phosphorylation ; drug effects ; Rats ; Rats, Wistar ; tau Proteins ; metabolism