Self-help cognitive behavior therapy (CBT) is a useful approach for the treatment of psychological problems. Recent research on the effectiveness of self-help internet-based CBT (ICBT) indicates that the paradigm moderately improves psychological problems. Furthermore, previous studies have shown that food and drinks containing supplements improve various health conditions. We investigated the effect of a brief self-help ICBT administered with a supplement drink on psychological well-being and somatic symptoms.

BACKGROUND:Computerized cognitive behaviour therapy (CCBT) programs can provide a useful self-help approach to the treatment of psychological problems. Previous studies have shown that CCBT has moderate effects on depression, insomnia, and anxiety. The present study investigated whether a supplement drink that includes L-carnosine enhances the effect of CCBT on psychological well-being.METHODS:Eighty-seven participants were randomly allocated to a control group, CCBT, or CCBT with supplement drink. The CCBT and CCBT with supplement drink groups received six weekly self-help CCBT program instalments, which consisted of psycho-education about stress management and coping, behaviour activation, and cognitive restructuring. The CCBT group consumed a bottle of the supplement soft drink every morning through the 6 weeks. This program was delivered by an e-learning system on demand and also included a self-help guidebook. Seventy-two participants completed the program or were assess at the end of the study.RESULTS:ANOVA revealed that there were significant interactions (times × groups) for POMS tension-anxiety and fatigue. The CCBT group showed significantly improved tension-anxiety scores, whereas the CCBT with drink group showed significant improvements on fatigue.CONCLUSION:The self-help CCBT program reduced the subjective experience of tension-anxiety in this group of workers. The addition of a supplement drink enhanced the effect of CCBT on fatigue, providing one possible approach to enhancement of such programs.TRIAL REGISTRATION:This study was registered on September 2, 2016 at UMIN. The registration number is UMIN000023903.

It is reported that the circadian timing system may be included in the mechanism by which l-carnosine (Car) affects multiple physiological alterations including blood glucose, cardiovascular functions etc. However, it is not clear whether Car would affect the circadian rhythm of clock genes in the heart and what is the possible mechanism underlying. To clarify these issues, we compared the effects of Car on the expression of circadian genes in the heart of normal and vagotomized rats under control and jet lag conditions. The normal and vagotomized (va) male Wistar rats were divided into three groups respectively. The control and va-Control groups (fed with regular chow) were sampled before the reversal of LD cycle and feeding schedule (day 0). The normal and va-Normal resetting groups (fed with regular chow) as well as the Car and va-Car resetting groups (fed with Car-containing diet) were sampled on day 3 and day 5 after the experimental jet lag. Car-feeding obviously enhanced the resetting rates of clock genes (Bmal1, Dec1, Cry1) in the heart of normal rats after the experimental jet lag. The unilateral surgical vagotomy didn’t alter the diurnal expression patterns and resetting rates of the examined clock genes in normal diet feeding rats. In contrast, it abolished the Car-induced rapid resetting of the clock genes in the heart. Therefore, Car feeding plays a positive role in the circadian resynchronization of the heart clock, which is underlied by the autonomic nervous system.

Cyclophosphamide is one of the most widely used chemotherapeutic agents in treating cancers. Chemotherapy drug-induced oxidative stress produces side effects. The severity of myelosuppression increases with a high dose of cyclophosphamide. Chicken soup or chicken essence, a traditional Chinese aliment, is a popular health supplement for patients with cancers or other diseases in Asia. As a major functional component of chicken meat extract, carnosine (beta-alanyl-L-histidine), a dipeptide of the amino acids beta-alanine and histidine, has been shown to have strong antioxidant activities. In the present study, we investigated the effects of carnosine on hematopoietic suppression in mice treated with cyclophosphamide. As expected, we found that cyclophosphamide administration (with a single dose of 150 mg/kg) induced a rapid (within 24 hours) and severe hematopoietic suppression in mice. We further showed that carnosine administration (100 mg/kg/day or 200 mg/kg/day for continuous seven days) could substantially improve suppressed hematopoietic functions and accelerate the recovery of leukocyte counts, bone marrow spontaneous proliferation, colony stimulating activity (CSA) in serum, and production of endogenous cytokines such as interleukin-3 (IL-3) and stem cell factor (SCF). These results indicate that carnosine has the potential to promote the recovery from hematopoietic suppression induced by cyclophosphamide. Our data suggest that carnosine holds a potential in clinical application to minimize the side effects induced by chemotherapeutic agents such as cyclophosphamide and thus will substantially improve the overall anti-tumor effects of the standard chemotherapies.

It is now well established that the developing embryo is very sensitive to oxidative stress, which is a contributing factor to pregnancy-related disorders. However, little is known about the effects of reactive oxygen species (ROS) on the embryonic cardiovascular system due to a lack of appropriate ROS control method in the placenta. In this study, a small molecule called 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH), a free radicals generator, was used to study the effects of oxidative stress on the cardiovascular system during chick embryo development. When nine-day-old (stage HH 35) chick embryos were treated with different concentrations of AAPH inside the air chamber, it was established that the LD50 value for AAPH was 10 µmol/egg. At this concentration, AAPH was found to significantly reduce the density of blood vessel plexus that was developed in the chorioallantoic membrane (CAM) of HH 35 chick embryos. Impacts of AAPH on younger embryos were also examined and discovered that it inhibited the development of vascular plexus on yolk sac in HH 18 embryos. AAPH also dramatically repressed the development of blood islands in HH 3+ embryos. These results implied that AAPH-induced oxidative stress could impair the whole developmental processes associated with vasculogenesis and angiogenesis. Furthermore, we observed heart enlargement in the HH 40 embryo following AAPH treatment, where the left ventricle and interventricular septum were found to be thickened in a dose-dependent manner due to myocardiac cell hypertrophy. In conclusion, oxidative stress, induced by AAPH, could lead to damage of the cardiovascular system in the developing chick embryo. The current study also provided a new developmental model, as an alternative for animal and cell models, for testing small molecules and drugs that have anti-oxidative activities.

The aim of this study was to investigate the effects of the essence of chicken on brain function by near-infrared spectroscopy. Twelve healthy elderly subjects took the essence of chicken or a placebo for 7 d in a double-blind cross-over design study. Changes in oxy-hemoglobin concentrations in the bilateral prefrontal areas of the brain were measured while the subjects performed the simple reaction task, the Groton Maze Learning Test, and the working memory task. In the latter case, there were significant interactions in the changes in oxy-hemoglobin concentrations between treatment and period of intake according to two-way repeated ANOVA. The changes in oxy-hemoglobin concentrations significantly increased in several regions of the prefrontal areas of the brain in those taking essence of chicken for 7 d. These results suggest that essence of chicken is useful as a nutritional supplement to enhance or maintain brain function in the elderly.

Background: Fatigue is a common symptom in modern society. There has been a recent resurgence of interest in traditional remedies for fatigue. Chicken essence, which is rich in anserine and carnosine, has been widely taken in Asian countries as a traditional remedy with various aims, including attenuation of physical and mental fatigue. However, the evidence for its efficacy specifically for mental fatigue remains unclear. We examined the effect of essence of chicken on mental fatigue in humans, using our established fatigue-inducing task and evaluation methods.Material/Methods: In this placebo-controlled crossover study, 20 healthy male volunteers were randomized to receive daily oral administration of essence of chicken or placebo drink provided by Cerebos Pacific Ltd. via Suntory holdings Ltd. for 4 weeks. The participants performed 2-back test trials as a fatigue-inducing mental task and then had a rest session. Just before and after each session, they completed cognitive task trials focusing on selective attention to evaluate the level of mental fatigue.Results: After essence of chicken intake for 1 and 4 weeks, the reaction times on the cognitive task trials after the rest session were significantly shorter than those at baseline, and significant changes were not observed with placebo intake. The reaction times before and after the fatigue-inducing session were not altered by either essence of chicken or placebo intake.Conclusions: We showed that daily intake of essence of chicken could be effective for the recovery from mental fatigue and is a promising candidate for use as an anti-fatigue food.

Carnosine (β-alanyl-L-histidine), a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Killer (NK) cells were obviously decreased. Results also demonstrated that restraint stress decreased the cytotoxic activity of NK cells per spleen (LU(10)/spleen) while the activity of a single NK cell (LU(10)/10(6) cells) was not changed. However, oral administration of carnosine (150 and 300 mg/kg) increased spleen index and number of spleen lymphocytes (including NK cells), and elevated the cytotoxic activity of NK cells per spleen in restraint-stressed mice. These results indicated that carnosine ameliorated stress-evoked immunocompromise through spleen lymphocyte number maintenance. Carnosine was further found to reduce stress-induced elevation of plasma corticosterone level. On the other hand, results showed that carnosine and RU486 (a glucocorticoids receptor antagonist) treatment prevented the reduction in mitochondrion membrane potential and the release of mitochondrial cytochrome c into cytoplasm, increased Bcl-2/Bax mRNA ratio, as well as decreased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in spleen lymphocytes of stressed mice. The results above suggested that the maintenance of spleen lymphocyte number by carnosine was related with the inhibition of lymphocytes apoptosis caused by glucocorticoids overflow. The stimulation of lymphocyte proliferation by carnosine also contributed to the maintenance of spleen lymphocyte number in stressed mice. In view of the elevated histamine level, the anti-stress effects of carnosine on restraint-evoked immunocompromise might be via carnosine-histamine metabolic pathway. Taken together, carnosine maintained spleen lymphocyte number by inhibiting lymphocyte apoptosis and stimulating lymphocyte proliferation, thus prevented immunocompromise in restraint-stressed mice.

In this study, we investigated the protective effects of the extract of chicken meat (EC) on liver damage in mice caused by restraint stress. Our results showed that 18 h of restraint stress-induced liver damage was marked by an increase of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. However, oral administration of EC (0.12 and 0.24 mL/10 g per day, 7 d) was found to reduce the increased plasma ALT and AST levels in stressed mice. Meanwhile, EC significantly decreased the contents of malondialdehyde and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) in plasma or liver of stressed mice. The gene expressions of anti-oxidative enzymes (Cu/Zn-SOD, Mn-SOD and GPX) were also up-regulated in the EC-treated group when compared with the stressed group. In addition, EC administration was found to resist a stress-induced increase of plasma corticosterone levels and down-regulation of liver glucocorticoid receptor gene expression. These results suggested that EC could protect against restraint stress-induced liver damage by smoothing stress and promoting antioxidative processes.

Diketopiperazines (DKPs) are naturally-occurring cyclic dipeptides with a small structure and are found in many organisms and in large amounts in some foods and beverages. We found that a chicken essence beverage, which is popular among Southeast Asians as a traditional remedy and a rich source of DKPs, inhibited the serotonin transporter (SERT) and suppressed serotonin uptake from rat brain synaptosomes, which prompted us to isolate and identify the active substance(s). We purified a SERT inhibitor from the chicken essence beverage and identified it as the DKP cyclo(L-Phe-L-Phe). Interestingly, it was a naturally occurring dual inhibitor that inhibited both SERT and acetylcholinesterase (AChE) in vitro. The DKP increased extracellular levels of the cerebral monoamines serotonin, norepinephrine, and dopamine in the medial prefrontal cortex and acetylcholine in the ventral hippocampus of freely moving rats when administered orally. Moreover, cyclo(L-Phe-L-Phe) significantly shortened escape latency in the water maze test in depressed mice previously subjected to a repeated open-space swimming task, which induces a depression-like state. Cyclo(L-Phe-L-Phe) also significantly improved accuracy rates in a radial maze test in rats and increased step-through latencies in a passive avoidance test in mice with scopolamine-induced amnesia. These animal test results suggest that cyclo(L-Phe-L-Phe), which is present abundantly in some foods such as chicken essence, may abrogate the onset of depression and, thus, contribute to preventing the development of Alzheimer's disease and other dementia, because senile depression is a risk factor for dementia.

Carnosine is a natural dipeptide that has shown multiple benefits in the treatment of various diseases. This study investigated the ameliorative effects of carnosine on glucose metabolism in restraint-stressed mice. Our results showed that restraint stress could significantly influence glucose metabolism, as reflected by lowered glucose tolerance, hepatic and muscle glycogen content, and increased plasma corticosterone concentration in mice. Oral administration of carnosine (150 and 300 mg/kg) not only reverted stress-induced decline in glucose tolerance and glycogen content in liver and muscle, but also reduced plasma corticosterone level. Carnosine has also significantly suppressed mRNA expression of glucose-6-phosphatase, while elevating glycogen synthase 2, glucokinase and glucose transporter 2 expressions in the liver. The obtained results demonstrated the harmful effects induced by restraint stress, while proving that carnosine could ameliorate stress-induced glucose metabolism disturbance. It is presumable that carnosine exerts its anti-stress effects by indirectly affecting the histaminergic neuron system, modulating the stress-activated hypothalamic pituitary adrenal axis and improving glucose metabolism through regulation of the enzymes in the glucose metabolic pathways.

BRAND's Essence of Chicken (BEC) has been widely used as a traditional remedy by people in Southeast Asia, which is proved to have an effect on the central nervous system (CNS) and autonomic nervous system (ANS). However, whether and how BEC consumption may affect mammalian circadian system is still largely unknown. In the present study, we investigated the effect of BEC feeding on the adaptation of circadian clocks to the experimental jet lag in rats. After the 12-h experimental jet lag through extending the light period, BEC feeding markedly facilitated the re-entrainment of all examined clock genes (Bmal1, Cry1, Per1, and Per2) in the pineal gland. The resetting time course of pineal clock genes was reduced from 7 days to only 3-5 days by BEC feeding, which was almost equal to the effect of melatonin feeding. In the liver clock, the facilitating effect of BEC feeding was mainly displayed in the re-entrainment of Bmal1 and Per2 by shortening their resetting processes for nearly 2 days. However, the resetting rate of locomotor activity rhythm was not affected by BEC feeding, suggesting that BEC might be unable to affect the behavioral rhythm.

The aim of the present study is to investigate the protective effect of bilberry extract on liver damage in restraint stressed mice. A remarkable increase in alanine aminotransferase (ALT) and reactive oxygen species (ROS) levels was observed in stressed mice. Treatment with bilberry extract restored ALT and ROS to normal levels, and enhanced mitochondrial complex II activity that was lowered in restraint stressed mice. The mitochondrial electron transfer chain (ETC)-related gene expression was measured by RT-PCR, and a significant up-regulation of complex II mRNA was observed for SDHA, B, C and D mRNA in bilberry extract-treated group compared with that in stressed group. Bilberry extract administration also profoundly elevated the Na+-K+-ATPase activity and mitochondria membrane potential (∆Ψm), which was reduced in the stressed group. Bilberry extract exhibited protective effect by scavenging free radicals and attenuating mitochondrial dysfunction in the liver of restraint stressed mice. It may be used as a promising therapeutic agent in preventing and delaying the life-related disease.

The present study was conducted to investigate the effects of histamine on the lipid metabolic disorder in mice loaded with restraint stress. When Kun Ming (KM) mice were exposed to restraint stress for 20 h, the histamine level in both plasma and cerebral regions significantly increased (P<0.01). Moreover, when a lipid emulsion (10% Intralipid) was injected intravenously into the mice, the elimination period of plasma triglyceride was prolonged in the restraint group. Plasma triglyceride was 523 +/- 44 mg/dl at 35 min after the Intralipid administration in the restraint stress group, while it was 436 +/- 41 mg/dl in the restrained mice given histamine at a dose of 50 mg/kg. The improved plasma triglyceride metabolism was well explained by the observations of the significantly up-regulated hepatic triglyceride lipase (HTGL) activity and mRNA expression in response to histamine. These results suggested that the effects of stress-induced histamine on lipid metabolic disorder in mice loaded with restraint stress arose from its anti-stress action and promotion of lipase activity.