The gut microbiota mediates the protective effects of anserine supplementation on hyperuricaemia and associated renal inflammation.

Hyperuricaemia is a disease associated with elevated serum uric acid content, which has emerged rapidly in recent decades. The drugs used to treat clinical hyperuricaemia have side effects, and their safety is poor. However, anserine is a natural carnosine derivative that shows an anti-hyperuricaemic effect. A previous study demonstrated that anserine inhibits uric acid synthesis and promotes uric acid excretion, but there is no evidence regarding the effect of anserine from the perspective of the gut microbiota. In this study, the anti-hyperuricaemic and anti-inflammatory effects of anserine were explored in a diet-induced hyperuricaemic mouse model. Anserine alleviated hyperuricaemia and renal inflammation phenotypes, inhibited uric acid biosynthesis, promoted uric acid excretion, and inhibited NLRP3 inflammasome and TLR4/MyD88/NF-κB signalling pathway activation. The results showed that the anti-hyperuricaemic effect of anserine was dependent on the gut microbiota in the germ-free mice experiment. Furthermore, anserine treatment reversed gut microbiota dysbiosis, repaired the intestinal epithelial barrier and increased short-chain fatty acid production. Moreover, the anti-hyperuricaemic effect of anserine was transmissible by transplanting the faecal microbiota from anserine-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, we identified a new and safe prebiotic material to alleviate hyperuricaemia and provided ideas for the development of oligopeptides.

Anserine Reverses Exercise-Induced Oxidative Stress and Preserves Cellular Homeostasis in Healthy Men.

The study tested whether anserine (beta-alanyl-3-methyl-l-histidine), the active ingredient of chicken essence affects exercise-induced oxidative stress, cell integrity, and haematology biomarkers. In a randomized placebo-controlled repeated-measures design, ten healthy men ingested anserine in either a low dose (ANS-LD) 15 mg.kg-1.bw-1, high dose (ANS-HD) 30 mg.kg-1.bw-1, or placebo (PLA), following an exercise challenge (time to exhaustion), on three separate occasions. Anserine supplementation increased superoxide dismutase (SOD) by 50% (p < 0.001, effect size d = 0.8 for both ANS-LD and ANS-HD), and preserved catalase (CAT) activity suggesting an improved antioxidant activity. However, both ANS-LD and ANS-HD elevated glutathione disulfide (GSSG), (both p < 0.001, main treatment effect), and consequently lowered the glutathione to glutathione disulfide (GSH/GSSG) ratio compared with PLA (p < 0.01, main treatment effect), without significant effects on thiobarbituric acid active reactive substances (TBARS). Exercise-induced cell damage biomarkers of glutamic-oxaloacetic transaminase (GOT) and myoglobin were unaffected by anserine. There were slight but significant elevations in glutamate pyruvate transaminase (GPT) and creatine kinase isoenzyme (CKMB), especially in ANS-HD (p < 0.05) compared with ANS-LD or PLA. Haematological biomarkers were largely unaffected by anserine, its dose, and without interaction with post exercise time-course. However, compared with ANS-LD and PLA, ANS-HD increased the mean cell volume (MCV), and decreased the mean corpuscular haemoglobin concentration (MCHC) (p < 0.001). Anserine preserves cellular homoeostasis through enhanced antioxidant activity and protects cell integrity in healthy men, which is important for chronic disease prevention. However, anserine temporal elevated exercise-induced cell-damage, together with enhanced antioxidant activity and haematological responses suggest an augmented exercise-induced adaptative response and recovery.

Effects of Anserine/Carnosine Supplementation on Mild Cognitive Impairment with APOE4.

BACKGROUND: Oral supplementation of anserine/carnosine helps preserve cognitive functions in healthy older adults. Mild cognitive impairment (MCI) is a transition between cognitive-normal and dementia. Therefore, it needs to investigate whether anserine/carnosine supplementation (ACS) has effects on subjects with MCI. METHODS: A randomized, double-blind, placebo-controlled 12-week trial was performed. Fifty-four subjects with MCI were randomized to an active group ingesting 750 mg of anserine and 250 mg of carnosine per day or a placebo (1:1). Evaluation of cognitive change was conducted utilizing a psychometric test battery. RESULTS: The score improvement in the global Clinical Dementia Rating (gloCDR) was superior in the active group than placebo (p = 0.023). No beneficial effect in the active group was detected in the other psychometric tests including the Mini-Mental State Examination (MMSE), the Wechsler Memory Scale, and the Alzheimer's Disease Assessment Scale (ADAS). When APOE4 positive (APOE4 (+)) or negative (APOE4 (-)) subjects were separately analyzed, beneficial change in the APOE4 (+) subjects was observed in MMSE (p = 0.025) as well as in gloCDR (p = 0.026). CONCLUSIONS: The present study might suggest that protective effects against cognitive decline in APOE4 (+) MCI subjects exist.

The Effects of Ginsenosides and Anserine on the Up-Regulation of Renal Aquaporins 1-4 in Hyperuricemic Mice.

Hyperuricemia is a metabolic disease of the kidney that results in decreased uric acid excretion. Here, we aimed to investigate the effects of ginsenosides and anserine on hyperuricemia and the expression of aquaporin (AQP) 1-4, which are indicators of renal excretion. Ginsenosides and anserine were administered separately or together after the establishment of hyperuricemia with adenine in BALB/c mice. Renal function indexes such as serum uric acid, creatinine, and urea nitrogen were measured in each group of mice, and the expression of AQP1-4 in renal tissues was detected. Serum uric acid and urea nitrogen were decreased in the ginsenoside and the anserine +UA groups. Meanwhile, the uric acid excretion and clearance rate were clearly increased in the co-treatment +UA group (p<0.05). Moreover, ginsenosides or anserine ginsenosides or anserine alone and treatment with both increased the expression of AQP1-4; however, the synergistic effects were more significantly enhanced (p<0.01). We provide the first reported evidence that ginsenosides and anserine have synergistic effects on uric acid excretion. The improvement in renal function in hyperuricemic mice after treatment with ginsenosides and anserine may result from up-regulation of AQP1-4 expressions.

Anserine/Carnosine Supplementation Suppresses the Expression of the Inflammatory Chemokine CCL24 in Peripheral Blood Mononuclear Cells from Elderly People.

Our goal was to determine whether anserine/carnosine supplementation (ACS) suppresses chemokine levels in elderly people. In a double-blind randomized controlled trial, volunteers were assigned to the ACS or placebo group (1:1). Sixty healthy elderly volunteers (active, n = 30; placebo, n = 30) completed the study. The ACS group was administered 1.0 g of anserine/carnosine (3:1) for 3 months. A microarray analysis and subsequent quantitative real-time polymerase chain reaction (qRT-PCR) analysis of peripheral blood mononuclear cells (PBMCs) showed decreased expression of CCL24, an inflammatory chemokine (p < 0.05). Verbal memory, assessed using the Wechsler memory scale-logical memory, was preserved in the ACS group. An age-restricted sub-analysis showed significant verbal memory preservation by ACS in participants who were in their 60s (active, n = 12; placebo, n = 9; p = 0.048) and 70s (active, n = 7; placebo, n = 11; p = 0.017). The suppression of CCL24 expression was greatest in people who were in their 70s (p < 0.01). There was a significant correlation between the preservation of verbal memory and suppression of CCL24 expression in the group that was in the 70s (Poisson correlation, r = 0.46, p < 0.05). These results suggest that ACS may preserve verbal episodic memory, probably owing to CCL24 suppression in the blood, especially in elderly participants.

Anserine and carnosine supplementation in the elderly: Effects on cognitive functioning and physical capacity.

The aim of this study was to investigate the potential beneficial effects of dietary anserine and carnosine (CRC) supplementation on cognitive functioning and physical activity of the elderly. The fifty-six subjects (65+) were allocated to the CRC group or placebo group at a 1:1 ratio. The double-blind procedure was used. Data were collected at the baseline and after 13-weeks of supplementation. In the follow up procedure fifty one subjects took part. Chicken meat extract (CME) containing 40% of CRC components (2:1 ratio of anserine to carnosine) was administered 2.5 g per day which allowed to rich the level of 1g CRC in dipeptides supplement. The cognitive function, physical capacity, body measurements, blood pressure and heart rate (HR) were assessed. After supplementation Body Mass Index (BMI) decreased significantly (p<0.05) in the CRC group performance comparing the placebo group. In two of six Senior Fitness Test the scores increased significantly (p<0.05) in CRC group comparing to the placebo group. The perceived exertion differed significantly (p<0.05) at the baseline and after follow up at the CRC group. The mean values of the Short Test of Mental Status (STMS) scores showed the significant (p<0.04) increase only in CRC group, in the subscores of construction/copying, abstraction and recall. Conducted anserine and carnosine supplementation in the elderly brings promising effects on cognitive functioning and physical capacity of participants. However, further studies are needed.