Neuroprotective effects of ProBeptigen/CMI-168 on aging-induced cognitive decline and neuroinflammation in mice: a comparison with essence of chicken.

Neuroinflammation and cognitive decline are the key pathological features in aging that bring detrimental impacts upon quality of life. However, there is no effective anti-aging pharmacological therapy thus far. Dietary supplements in particular essence of chicken (EC) has been found to be an effective remedy for alleviating mental stress and improving memory. In addition, a novel hydrolyzed chicken extract, ProBeptigen/CMI-168 (PB), showed beneficial effects on cognitive ability. However, the antiaging effect and possible mechanism of PB and EC are still unknown. Here, we investigated the antiaging effects of PB and EC on hippocampus-related cognitive decline and neuroinflammation in aged mice. PB and EC were administered for 16 weeks in 10-month-old mice. Both PB and EC treatments ameliorated age-related deterioration of learning and memory, and attenuated oxidative stress and inflammation in the hippocampus. These results were associated with decreased inflammatory cytokine levels and increased neurotransmitter levels in the hippocampus. The overall effects of improving aging-induced cognitive decline were more robust in PB-treated mice, while EC was effective in decreasing oxidative stress and inflammation. Moreover, alterations in the diversity and composition of the gut microbiota in aged mice were also regulated by both PB and EC, which induced distinguished features in the gut microbiota and their related functions. This study showed that PB exerts neuroprotective effects in aged mice, the mechanism of which might be different from that of EC. Therefore, PB has a potential as dietary supplement for ameliorating cognitive dysfunction and neuroinflammation in elderly individuals.

Daily consumption of essence of chicken improves cognitive function: a systematically searched meta-analysis of randomized controlled trials.

Essence of chicken (EC) is a dietary supplement with potential benefits on one's cognitive performance. The purpose of this meta-analysis is to evaluate the effects of consuming EC on cognitive function, applying extensively represented domains. Six databases were systematically searched to yield 1760 articles. These articles were independently screened to obtain 8 eligible articles with a pooled population of 794 subjects which is more than twice the population size considered in the previous meta-analyses. Largely, favorable effects on cognitive function were observed following daily EC intake, specifically in the working memory domain (standardized mean difference: 0.31, 95% CI: 0.16, 0.46), one of the core components in executive function which showed statistically significant results. Furthermore, the observed results were also robust to sensitivity analyses and subgroup analyses. This suggests that when consumed daily, EC may improve the mental processing aspect of cognitive function amongst the healthy population.

Hydrolyzed Chicken Extract (ProBeptigen®) on Cognitive Function in Healthy Middle-Aged People: A Randomized Double-Blind Trial.

Cognitive decline is an important issue of global public health. Cognitive aging might begin at middle adulthood, the period particularly vulnerable to stress in lifespan. Essence of chicken (EOC) has consistently demonstrated its beneficial effects on various cognitive domains as nutritional supplementation. This study primarily aimed to examine the cognitive enhancement effects of ProBeptigen® (previously named CMI-168), hydrolyzed peptides extracted from EOC, in healthy middle-aged people under mild stress. Ninety healthy subjects were randomly assigned into the ProBeptigen® or placebo group for eight weeks. Neurocognitive assessment, event-related potentials (ERPs), and blood tests were conducted before, during, and after the treatment. The ProBeptigen® group outperformed placebo group on Logical Memory subtests of Wechsler Memory Scale-third edition (WMS-III) and Spatial Working Memory task in the Cambridge Neuropsychological Test Automated Battery (CANTAB). The anti-inflammatory effects of ProBeptigen® in humans were also confirmed, with progressively declining high-sensitivity C-reactive protein (hs-CRP) levels. Regular dietary supplementation of ProBeptigen® is suggested to improve verbal short- and long-term memory as well as spatial working memory, and reduce inflammation in middle-aged healthy individuals with stress. The effects of ProBeptigen® on cognition warrant further investigation. (NCT03612752).

A Hydrolyzed Chicken Extract CMI-168 Enhances Learning and Memory in Middle-Aged Mice.

There has been increasing evidence that consumption of dietary supplements or specific nutrients can influence cognitive processes and emotions. A proprietary chicken meat extraction, Chicken Meat Ingredient-168 (CMI-168), has previously been shown to enhance cognitive function in humans. However, the mechanism underlying the CMI-168-induced benefits remains unclear. In this study, we investigated the effects of CMI-168 on hippocampal neuroplasticity and memory function in middle-aged (9⁻12 months old) mice. The mice in the test group (termed the "CMI-168 group") were fed dietary pellets produced by mixing CMI-168 and normal laboratory mouse chow to provide a daily CMI-168 dose of 150 mg/kg of body weight for 6 weeks. The control mice (termed the "Chow group") were fed normal laboratory mouse chow pellets. CMI-168 supplementation did not affect the body weight gain, food intake, or exploratory behavior of the mice. In the novel object recognition test, the CMI-168 group showed better hippocampus-related non-spatial memory compared to the control Chow group. However, spatial memory examined by the Morris Water Maze test was similar between the two groups. There was also no significant difference in the induction and maintenance of long-term potentiation and dendritic complexity of the hippocampal cornu ammonis region 1 (CA1) neurons, as well as the levels of neuroplasticity-related proteins in the hippocampi of the CMI-168 and Chow groups. Interestingly, we observed that CMI-168 appeared to protect the mice against stress-induced weight loss. In conclusion, dietary supplementation of CMI-168 was found to improve learning and memory in middle-aged mice, independent of structural or functional changes in the hippocampus. The resilience to stress afforded by CMI-168 warrants further investigation.

Effects of Ganoderma lucidum and 'Essence of Chicken' on Physical Fatigue Recovery and Exercise Performance Improvement.

A fast-paced lifestyle, pressure from the environment and a heavy work load often cause extreme tiredness in modern life. Different kinds of nutritional supplements in the form of functional foods or traditional Chinese medicine, such as 'essence of chicken' and Ganoderma lucidum have been claimed to benefit physical performance and promote health. Previous studies have revealed that 'essence of chicken' or G. lucidum have a wide spectrum of biological activities. In this study, we combined these two ingredients together (designated as CEG) to evaluate their synergistic effects on physiological adaption on exercise fatigue and physical activities. The ICR strain mice were allocated as 0, 833, 1666, and 4165 mg/kg dose groups and administrated by oral gavage consecutively for 4 weeks. Physical activities including grip strength and aerobic endurance were evaluated. Various fatigue-associated biochemical variables such as lactate, BUN or CK were also evaluated. The levels of liver and muscle glycogen were measured as an indicator of energy storage at the end of the experiment. Safety assessments for supplementation were also evaluated. CEG supplementation significantly increased the endurance and grip strength and demonstrated beneficial effects on lactate production and clearance rate after an acute exercise challenge. The CEG supplementation significantly mitigated the BUN and CK indexes after extended exercise and elevated the glycogen content in the liver and muscle tissues. According to body composition, biochemical and histopathological data, daily administration of CEG for over 28 days (subacute toxicity) also demonstrated reasonable safety results for supplementation. Combined G. lucidum and 'essence of chicken' can significantly increase the exercise performance and improve fatigue recovery. It may also provide a viable alternative nutritional supplement for health promotion.

Effectiveness of Essence of Chicken on Cognitive Function Improvement: A Randomized Controlled Clinical Trial.

High-quality, adequately-powered clinical trials investigating the effect of Essence of Chicken (EC) on cognitive function are lacking. We conducted a randomized, double-blind, placebo-controlled clinical trial on healthy adult volunteers to determine the effect of EC on short-term memory, working memory, and selective and sustained attention. As a secondary objective, we evaluated baseline stress as a modifying factor by including treatment, stress and visit as main effects in a three-way ANOVA model. Cognitive function was evaluated at baseline, and Days 7 and 14. Data from 235 participants were analyzed on a per-protocol basis. The three-way interaction effect was significant (p = 0.020) in Digit Span Forward and further analyses showed EC improved test performance in moderate (p = 0.041) and severe stress (p = 0.065) but not in normal and mild stress subgroups. In Digit Span Backward, EC group showed greater improvement compared to placebo (p = 0.028), with 0.60 digits (8.50% improvement from baseline) more recalled on Day 7. No treatment or interaction effects were statistically significant in selective and sustained attention tests. Our findings support EC’s effect in improving mental processes used in working memory among healthy adults and short-term memory among healthy adults experiencing stress in daily life.

The involvement of sympathetic nervous system in essence of chicken-facilitated physiological adaption and circadian resetting.

AIM: The impact of the sympathetic nervous system (SNS) on the regulation of circadian rhythm and physiological functions is still not clear. Previous studies have found that essence of chicken (EC) supplementation facilitated the physiological adaption and circadian resetting in rats subjected to jet lag. Herein, the effects of SNS on the circadian clock and the hypothesis that EC-induced acceleration of circadian resetting is dependent on the SNS are investigated. MAIN METHODS: Male Wistar rats with superior cervical ganglionectomy (SCGx) were used to investigate the role of the SNS in circadian rhythm and physiological functions. SCGx rats were further fed with or without EC-containing diet for 2 weeks and subjected to artificial jet lag. KEY FINDINGS: Loss of SNS did not affect the circadian rhythm both in the hypothalamic suprachiasmatic nuclei (SCN) and peripheral clocks, including the liver and heart. The serum lipid levels were increased significantly in SCGx rats, together with the up-regulation of lipogenic gene expression in the liver and slight effect on serum hormones. The quicker resetting process of the clock genes in peripheral tissues of EC-fed rats was abolished after SCGx. In contrast, the phase shift of serum melatonin and corticosterone were faster in EC-fed rats, compared to that of control rats. SIGNIFICANCE: The SNS controls different aspects of physiological functions, and it has little effect on circadian system under normal light/dark condition. The effects EC on peripheral circadian synchrony and physiological functions were dependent on, at least partly, through the regulation of sympathetic nerve function.

Facilitated physiological adaptation to prolonged circadian disruption through dietary supplementation with essence of chicken.

Synchrony between circadian and metabolic processes is critical to the maintenance of energy homeostasis. Studies on essence of chicken (EC), a chicken meat extract rich in proteins, amino acids and peptides, showed its effectiveness in alleviating fatigue and promoting metabolism. A recent study revealed that it facilitated the re-entrainment of clock genes (Bmal1, Cry1, Dec1, Per1 and Per2) in the pineal gland and liver in a rat model of circadian disruption. Here, we investigated the role of EC-facilitated circadian synchrony in the maintenance of the energy homeostasis using a mouse model of prolonged circadian disruption. Prolonged circadian disruption (12 weeks) resulted in hepatic maladaptation, manifested by a mild but significant (p < 0.05) hepatomegaly, accompanied by disturbed hepatic lipid metabolism and liver injury (indicated by increased circulating hepatic enzymes). Evidently, there was marked elevations of hepatic inflammatory mediators (interleukin-1beta and interleukin-6), suggesting an underlying inflammation leading to the hepatic injury and functional impairment. Importantly, the disruption paradigm caused the decoupling between key metabolic regulators (e.g. mTOR and AMPK) and hepatic clock genes (Per1, Cry1, Dec1, Bmal1). Further, we showed that the loss of circadian synchrony between the master and hepatic clock genes (Per1, Cry1, Dec1, Bmal1) could be the underlying cause of the maladaptation. When supplemented with EC, the functional impairment and inflammation were abolished. The protective effects could be linked to its effectiveness in maintaining the synchrony between the master and hepatic clocks, and the resultant improved coupling of the circadian oscillators (Per1, Cry1, Dec1, Bmal1) and metabolic regulators (mTOR, AMPK). Overall, EC supplementation promoted the physiological adaptation to the prolonged circadian disruption through facilitation of endogenous circadian synchrony and the coupling of circadian oscillators and metabolic regulators. This forms an important basis for further elucidation of the physiological benefits of EC-facilitated circadian synchrony.

Co-ingestion of essence of chicken to moderate glycaemic response of bread.

Essence of chicken (EOC) beverage is a chicken meat extract, widely consumed in Asian countries for health benefits. EOC is a rich source of peptides and amino acids. White bread has become a popular staple food in all regions of Southeast Asia. A randomized controlled, crossover, non-blind trial was performed to investigate the role of EOC on glycaemic response (GR) of white bread. Ten healthy young subjects returned on five separate days for three glucose and two bread sessions. Subjects consumed bread or bread with EOC. The 120 min incremental area under the curve was significantly lower after consuming two bottles of EOC with bread than white bread alone. The glycaemic index (GI) of white bread was 83 and white bread with EOC 57. The co-ingestion of EOC may be a practical and simple way to reduce the GR of bread and other starch-based staples.

Effect of co-ingestion of amino acids with rice on glycaemic and insulinaemic response.

Consumption of high glycaemic index (GI) and glycaemic response (GR) food such as white rice has been implicated in the development of type 2 diabetes. Previous studies have reported the ability of individual amino acids to reduce GR of carbohydrate-rich foods. Because of the bitter flavour of amino acids, they have rarely been used to reduce GR. We now report the use of a palatable, preformed amino acid mixture in the form of essence of chicken. In all, sixteen healthy male Chinese were served 68 or 136 ml amino acid mixture together with rice, or 15 or 30 min before consumption of white rice. Postprandial blood glucose and plasma insulin concentrations were measured at fasting and every 15 min after consumption of the meal until 60 min after the consumption of the white rice. Subsequent blood samples were taken at 30-min intervals until 210 min. The co-ingestion of 68 ml of amino acid mixture with white rice produced the best results in reducing the peak blood glucose and GR of white rice without increasing the insulinaemic response. It is postulated that amino acid mixtures prime ß-cell insulin secretion and peripheral tissue uptake of glucose. The use of ready-to-drink amino acid mixtures may be a useful strategy for lowering the high-GI rice diets consumed in Asia.