Anserine, a Histidine-Containing Dipeptide, Suppresses Pressure Overload-Induced Systolic Dysfunction by Inhibiting Histone Acetyltransferase Activity of p300 in Mice.

Anserine, an imidazole dipeptide, is present in the muscles of birds and fish and has various bioactivities, such as anti-inflammatory and anti-fatigue effects. However, the effect of anserine on the development of heart failure remains unknown. We cultured primary cardiomyocytes with 0.03 mM to 10 mM anserine and stimulated them with phenylephrine for 48 h. Anserine significantly suppressed the phenylephrine-induced increases in cardiomyocyte hypertrophy, ANF and BNP mRNA levels, and histone H3K9 acetylation. An in vitro histone acetyltransferase (HAT) assay showed that anserine directly suppressed p300-HAT activity with an IC50 of 1.87 mM. Subsequently, 8-week-old male C57BL/6J mice were subjected to transverse aortic constriction (TAC) and were randomly assigned to receive daily oral treatment with anserine-containing material, Marine Active® (60 or 200 mg/kg anserine) or vehicle for 8 weeks. Echocardiography revealed that anserine 200 mg/kg significantly prevented the TAC-induced increase in left ventricular posterior wall thickness and the decrease in left ventricular fractional shortening. Moreover, anserine significantly suppressed the TAC-induced acetylation of histone H3K9. These results indicate that anserine suppresses TAC-induced systolic dysfunction, at least in part, by inhibiting p300-HAT activity. Anserine may be used as a pharmacological agent for human heart failure therapy.

l-Anserine Increases Muscle Differentiation and Muscle Contractility in Human Skeletal Muscle Cells.

l-Anserine, an imidazole peptide, has a variety of physiological activities, but its effects on skeletal muscle differentiation and muscle contractile force remain unknown. Thus, in this study, we investigated the effect of l-anserine on muscle differentiation and muscle contractile force in human skeletal muscle cells. In two-dimensional culture, 1 µM l-anserine significantly increased the myotube diameters (26.5 ± 1.71, 27.7 ± 1.08, and 28.8 ± 0.85 µm with 0, 0.1, and 1 µM l-anserine, respectively) and the expression levels of genes involved in muscle differentiation and the sarcomere structure. In three-dimensional culture, 1 µM l-anserine significantly increased the contractile force of engineered human skeletal muscle tissues cultured on a microdevice (1.99 ± 0.30, 2.17 ± 0.62, 2.66 ± 0.39, and 3.28 ± 0.85 µN with 0, 0.1, 0.5, and 1 µM l-anserine, respectively). l-Anserine also increased the myotube diameters and the proportion of myotubes with sarcomere structures in the cultured tissues. Furthermore, the histamine receptor 1 (H1R) antagonist attenuated the l-anserine-induced increase in the contractile force, suggesting the involvement of H1R in the mechanism of action of l-anserine. This study showed for the first time that l-anserine enhances muscle differentiation and muscle contractility via H1R.

Anti-Hyperuricemic Effect of Anserine Based on the Gut-Kidney Axis: Integrated Analysis of Metagenomics and Metabolomics.

Nowadays, developing effective intervention substances for hyperuricemia has become a public health issue. Herein, the therapeutic ability of anserine, a bioactive peptide, was validated through a comprehensive multiomics analysis of a rat model of hyperuricemia. Anserine was observed to improve liver and kidney function and modulate urate-related transporter expressions in the kidneys. Urine metabolomics showed that 15 and 9 metabolites were significantly increased and decreased, respectively, in hyperuricemic rats after the anserine intervention. Key metabolites such as fructose, xylose, methionine, erythronic acid, glucaric acid, pipecolic acid and trans-ferulic acid were associated with ameliorating kidney injury. Additionally, anserine regularly changed the gut microbiota, thereby ameliorating purine metabolism abnormalities and alleviating inflammatory responses. The integrated multiomics analysis indicated that Saccharomyces, Parasutterella excrementihominis and Emergencia timonensis were strongly associated with key differential metabolites. Therefore, we propose that anserine improved hyperuricemia via the gut-kidney axis, highlighting its potential in preventing and treating hyperuricemia.

Effects of dietary ß-alanine supplementation on growth performance, meat quality, carnosine content, amino acid composition and muscular antioxidant capacity in Chinese indigenous Ningxiang pig.

ß-alanine has been demonstrated to improve carcass traits and meat quality of animals. However, no research has been found on the effects of dietary ß-alanine in the meat quality control of finishing pigs, which are among the research focus. Therefore, this study aimed to evaluate the effects of dietary ß-alanine supplementation on growth performance, meat quality, carnosine content, amino acid composition and muscular antioxidant capacity of Chinese indigenous Ningxiang pigs. The treatments contained a basal diet (control, CON) and a basal diet supplemented with 600 mg/kg ß-alanine. Each treatment group consisted of five pens, with five pigs per pen. Results showed that compared with CON, supplemental ß-alanine did not affect the final body weight, average daily gain, average daily feed intake and the feed-to-gain ratio of pigs. Dietary ß-alanine supplementation tended to increase the pH45 min (p = 0.071) while decreasing the shear force (p = 0.085) and the drip loss (p = 0.091). Moreover, it improved (p < 0.05) the activities of glutathione peroxidase and catalase and lessened (p < 0.05) malondialdehyde concentration. Added ß-alanine in diets of finishing pigs could enhance the concentrations of arginine, alanine, and glutamate (p < 0.05) in the longissimus dorsi muscle and tended to raise the levels of cysteine, glycine and anserine (p = 0.060, p = 0.098 and p = 0.091 respectively). Taken together, our results showed that dietary ß-alanine supplementation contributed to the improvement of the carcass traits, meat quality and anserine content, the amelioration of muscle antioxidant capacity and the regulation of amino acid composition in Chinese indigenous Ningxiang pigs.

Anserine beneficial effects in hyperuricemic rats by inhibiting XOD, regulating uric acid transporter and repairing hepatorenal injury.

This study aims to investigate the anti-hyperuricemia effect and mechanism of anserine in hyperuricemic rats. Hyperuricemic rats were induced with a combination of 750 mg per kg bw d potassium oxazinate (PO) and 200 mg per kg bw d hypoxanthine for a week, and the rats were separately orally administered anserine (20, 40, 80 mg kg-1) and allopurinol (10 mg kg-1) for three weeks. The results show that the content of serum uric acid (SUA) decreased by approximately 40% and 60% after the intervention of anserine and allopurinol, respectively. The activity of superoxide dismutase (SOD) was increased and the levels of malondialdehyde (MDA), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were significantly decreased in the anserine groups. After the administration of anserine, the contents of blood urea nitrogen (BUN) and creatinine (Cr) were reduced in the kidney, and the levels of the proinflammatory cytokines IL-1ß, IL-6ß, TNF-α and TGF-ß and inflammatory cell infiltration were reduced in both the liver and kidney. Moreover, the gene expressions of xanthine oxidase (XOD), renal urate transporter 1 (URAT1) and glucose transporter type 9 (GLUT9) were downregulated by anserine administration, and the gene expressions of ATP-binding cassette transporter G2 (ABCG2), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) were upregulated at the same time. These findings suggest that hepatorenal injury was repaired by anserine, which further regulated the expression of hepatic XOD and renal URAT1, GLUT9, ABCG2, OAT1 and OAT3 to relieve hyperuricemia in rats.

The ergogenic effect of acute carnosine and anserine supplementation: dosing, timing, and underlying mechanism.

Background: Recent studies suggest that acute-combined carnosine and anserine supplementation has the potential to improve the performance of certain cycling protocols. Yet, data on optimal dose, timing of ingestion, effective exercise range, and mode of action are lacking. Three studies were conducted to establish dosing and timing guidelines concerning carnosine and anserine intake and to unravel the mechanism underlying the ergogenic effects. Methods: First, a dose response study A was conducted in which 11 men randomly received placebo, 10, 20, or 30 mg.kg-1 of both carnosine and anserine. They performed 3x maximal voluntary isometric contractions (MVC), followed by a 5 x 6 s repeated cycling sprint ability test (RSA), once before the supplement and 30 and 60 minutes after. In a second study, 15 men performed 3x MVCs with femoral nerve electrical stimulation, followed by an RSA test, once before 30 mg.kg-1 carnosine and anserine and 60 minutes after. Finally, in study C, eight men performed a high intensity cycling training after randomly ingesting 30 mg.kg-1 of carnosine and anserine, a placebo or antihistamines (reduce post-exercise blood flow) to investigate effects on muscle perfusion. Results: Study A showed a 3% peak power (p = 0.0005; 95% CI = 0.07 to 0.27; ES = 0.91) and 4.5% peak torque (p = 0.0006; 95% CI = 0.12 to 0.50; ES = 0.87) improvement on RSA and MVC, with 30 mg.kg-1 carnosine + anserine ingestion 60 minutes before the performance yielding the best results. Study B found no performance improvement on group level; however, a negative correlation (r = -0.54; p = 0.0053; 95% CI = -0.77 to -0.19) was found between carnosinase enzyme activity (responsible for carnosine and anserine breakdown) and performance improvement. No effect of the supplement on neuromuscular function nor on muscle perfusion was found. Conclusions: These studies reveal that acute ingestion of 30 mg.kg-1 of both carnosine and anserine, 60 minutes before a high intensity exercise, can potentially improve performance, such as short cycling sprints or maximal muscle contractions. Subjects with lower carnosinase activity, and thus a slower breakdown of circulating dipeptides, appear to benefit more from this ergogenic effect. Finally, neither the involvement of a direct effect on neuromuscular function, nor an indirect effect on recovery through increased muscle perfusion could be confirmed as potential mechanism of action. The ergogenic mechanism therefore remains elusive.

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.

Ergogenic effect of pre-exercise chicken broth ingestion on a high-intensity cycling time-trial.

BACKGROUND: chicken meat extract is a popular functional food in Asia. It is rich in the bioactive compounds carnosine and anserine, two histidine-containing dipeptides (HCD). Studies suggest that acute pre-exercise ingestion of chicken extracts has important applications towards exercise performance and fatigue control, but the evidence is equivocal. This study aimed to evaluate the ergogenic potential of the pre-exercise ingestion of a homemade chicken broth (CB) vs a placebo soup on a short-lasting, high-intensity cycling exercise. METHODS: fourteen men participated in this double-blind, placebo-controlled, crossover intervention study. Subjects ingested either CB, thereby receiving 46.4 mg/kg body weight of HCD, or a placebo soup (similar in taste without HCD) 40 min before an 8 min cycling time trial (TT) was performed. Venous blood samples were collected at arrival (fasted), before exercise and at 5 min recovery. Plasma HCD were measured with UPLC-MS/MS and glutathione (in red blood cells) was measured through HPLC. Capillary blood samples were collected at different timepoints before and after exercise. RESULTS: a significant improvement (p = 0.033; 5.2%) of the 8 min TT mean power was observed after CB supplementation compared to placebo. Post-exercise plasma carnosine (p <  0.05) and anserine (p <  0.001) was significantly increased after CB supplementation and not following placebo. No significant effect of CB supplementation was observed either on blood glutathione levels, nor on capillary blood analysis. CONCLUSIONS: oral CB supplementation improved the 8 min TT performance albeit it did not affect the acid-base balance or oxidative status parameters. Further research should unravel the potential role and mechanisms of HCD, present in CB, in this ergogenic approach.

Anserine, HClO-scavenger, protected against cognitive decline in individuals with mild cognitive impairment.

Neuroinflammation has been recognized as a promising target when considering strategies for treating AD. In particular, it has been shown that neutrophils and MPO-mediated neuroinflammatory responses with the production of HClO play a role in the progression of AD. In this study, we aimed to evaluate the effects of anserine, a scavenger of HClO, on the protection of cognitive declines in persons with MCI. Fifty-eight elderly volunteers were screened, and 36 MCI individuals were assigned either to an active arm, who received 500 mg anserine per day, or a placebo arm, for 12-weeks. To assess cognitive function, we performed MMSE at baseline and after the ingestion. The data of the MMSE for 30 subjects who completed the follow-up tests were analyzed. A significant difference was detected in the change score of MMSE between the active arm (1.9 ± 2.0; n = 15) and the placebo arm (0 ± 2.8; n = 15) (p = 0.036). After the correction with the daily intake of anserine, the significance was elevated (p = 0.0176). Our results suggest that anserine protects elderly persons with MCI from cognitive declines by suppressing MPO-mediated neuroinflammatory responses.

Influence of Imidazole-Dipeptides on Cognitive Status and Preservation in Elders: A Narrative Review.

The worldwide increase in the number of patients with dementia is becoming a growing problem, while Alzheimer's disease (AD), a primary neurodegenerative disorder, accounts for more than 70% of all dementia cases. Research on the prevention or reduction of AD occurrence through food ingredients has been widely conducted. In particular, histidine-containing dipeptides, also known as imidazole dipeptides derived from meat, have received much attention. Imidazole dipeptides are abundant in meats such as poultry, fish, and pork. As evidenced by data from recent human intervention trials conducted worldwide, daily supplementation of carnosine and anserine, which are both imidazole dipeptides, can improve memory loss in the elderly and reduce the risk of developing AD. This article also summarizes the latest researches on the biochemical properties of imidazole dipeptides and their effects on animal models associated with age-related cognitive decline. In this review, we focus on the results of human intervention studies using supplements of poultry-derived imidazole dipeptides, including anserine and carnosine, affecting the preservation of cognitive function in the elderly, and discuss how imidazole dipeptides act in the brain to prevent age-related cognitive decline and the onset of dementia.

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.

A carnosine analog with therapeutic potentials in the treatment of disorders related to oxidative stress.

Interactive relationships among metabolism, mitochondrial dysfunction and inflammation at skeletal muscle level play a key role in the pathogenesis of disorders related to oxidative stress. Mitochondrial dysfunction and oxidative stress result in cellular energy deficiency, inflammation and cell death inducing a vicious cycle that promotes muscle wasting. The histidine-containing dipeptides, carnosine and anserine, are carbonyl scavengers whose cytoprotective contributions extend beyond the antioxidant defence, but the physiological meaning of these capacities is actually limited. In the present study, we compared and investigated the potential protective effects of three different histidine-containing dipeptides: carnosine, anserine and carnosinol, a carnosine-mimetic new compound, against oxidative stress induction in rat L6 skeletal muscle cells. The hydrogen peroxide induced-oxidative stress significantly altered cell morphology, induced apoptosis, oxidative stress and inflammation, decreased mitochondrial peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)/sirtuin3 pathway and the antioxidant system. Notably, all three investigated dipeptides in the present study, with a different extent and in a concentration-dependent manner, reduced myotube oxidative stress, apoptosis and inflammation. The present study underlined that carnosinol, maintaining the safety condition of carnosine and anserine, was the more efficient studied dipeptide in the preservation of mitochondrial environment mediated by PGC-1α and sirtuin3 expression and thereby in the reduction of oxidative stress-related alterations in this in vitro skeletal muscle model. Furthermore, we observed that carnosinol's antioxidant effects are not blocked inhibiting sirtuin3, but are maintained with almost the same extend, indicating its multiple capacities of reactive carbonyl species-scavenging and of mitochondrial modulation through PGC-1α. In conclusion, carnosinol retained and surpassed the efficacy of the well-known investigated histidine-containing dipeptides improving oxidative stress, inflammation and also cell metabolism and so becoming a greatly promising therapeutic carnosine derivate.

A zebrafish (danio rerio) model for high-throughput screening food and drugs with uric acid-lowering activity.

With co-treatment of potassium oxonate (PO) and xanthine sodium salt (XSS), a zebrafish larva model of acute hyperuricemia has been constructed for the first time. The results show PO 200 µM + XSS 10 µM, PO 300 µM + XSS 15 µM, and PO 400 µM + XSS 20 µM can significantly increase the level of uric acid in the zebrafish larvae (P < 0.05), the concentrations as described above can be used to construct the zebrafish larvae model of acute hyperuricemia. At the same time, treatment of allopurinol (APL, one of the hyperuricemia drugs) at 2000 µM (P < 0.001) and treatment of anserine (ASE) at 200 µM (P < 0.05) could significantly decrease the level of uric acid in the model group which received PO 200 µM + XSS 10 µM, which demonstrate that such model could offer a new robust approach for high-throughput screening of food and drugs with uric acid-lowering activity.

Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People.

Our goal in this study was to determine whether or not anserine/carnosine supplementation (ACS) is capable of preserving cognitive function of elderly people. In a double-blind randomized controlled trial, volunteers were randomly assigned to an ACS or placebo group at a 1:1 ratio. The ACS group took 1.0 g of an anserine/carnosine (3:1) formula daily for 3 months. Participants were evaluated by psychological tests before and after the 3-month supplementation period. Thirty-nine healthy elderly volunteers (60-78 years old) completed the follow-up tests. Among the tests, delayed recall verbal memory assessed by the Wechsler Memory Scale-Logical Memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0128). Blood analysis revealed a decreased secretion of inflammatory cytokines, including CCL-2 and IL-8, in the ACS group. MRI analysis using arterial spin labeling showed a suppression in the age-related decline in brain blood flow in the posterior cingulate cortex area in the ACS group, compared to the placebo group (p = 0.0248). In another randomized controlled trial, delayed recall verbal memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0202). These results collectively suggest that ACS may preserve verbal episodic memory and brain perfusion in elderly people, although further study is needed.

Protective activity of carnosine and anserine against zinc-induced neurotoxicity: a possible treatment for vascular dementia.

Carnosine (ß-alanyl-L-histidine) is a small dipeptide with numerous beneficial effects, including the maintenance of the acid-base balance, antioxidant properties, chelating agent, anti-crosslinking, and anti-glycation activities. High levels of carnosine and its analogue anserine (1-methyl carnosine) are found in skeletal muscle and the brain. Zinc (Zn)-induced neurotoxicity plays a crucial role in the pathogenesis of vascular dementia (VD), and carnosine inhibits Zn-induced neuronal death. Here, the protective activity of carnosine against Zn-induced neurotoxicity and its molecular mechanisms such as cellular Zn influx and Zn-induced gene expression were investigated using immortalised hypothalamic neurons (GT1-7 cells). Carnosine and anserine protected against Zn-induced neurotoxicity not by preventing increases in intracellular Zn(2+) but by participating in the regulation of the endoplasmic reticulum (ER) stress pathway and the activity-regulated cytoskeletal protein (Arc). Accordingly, carnosine and anserine protected against neurotoxicity induced by ER-stress inducers thapsigargin and tunicamycin. Hence, carnosine and anserine are expected to have future therapeutic potential for VD and other neurodegenerative diseases.

Effect of carnosine and related compounds on proliferation of cultured rat pheochromocytoma PC-12 cells.

The study was undertaken to determine the mechanism of carnosine effect on cell proliferation. We studied the effect of carnosine and its derivatives on cell cycle progression in cultured rat pheochromocytoma cells (PC-12). It was found that 48-h incubation of PC-12 cells with carnosine in concentrations of 10-50 mM led to deceleration of cell proliferation, reduction of G0/G1 peak, and accumulation of S- and G2/M-phase cells. Methylation of the carnosine molecule by 1N-position of the imidazole ring potentiated its effect on cell proliferation. Acetylation of the carnosine molecule by free ß-amino group attenuated its effect.

Effect of anserine ingestion on the hyperglycemia and autonomic nerves in rats and humans.

Anserine and L-carnosine are similar dipeptides synthesized by muscles of vertebrates. The functional role of anserine is unknown, although previous studies showed hypoglycemic effects of carnosine through autonomic nerves. Thus, we evaluated the effects of anserine on blood glucose levels and neural activities. Intraperitoneal administration of specific doses of anserine to hyperglycemic rats reduced hyperglycemia and plasma glucagon concentrations, whereas thioperamide eliminated the effects of anserine. Intraduodenal injection of 0.1 mg anserine to anesthetized rats after laparotomy suppressed sympathetic nerve activity and enhanced activity of the vagal gastric efferent. In addition, oral administration of anserine reduced blood glucose levels during oral glucose tolerance testing in humans. These results suggest the possibility that anserine might be a control factor for blood glucose, and that histaminergic nerves may be involved in the hypoglycemic effects of anserine.

Effects of anserine on the renal sympathetic nerve activity and blood pressure in urethane-anesthetized rats.

Previous studies have demonstrated that central injection of L-carnosine (beta-alynyl-L-histidine), dipeptide synthesized in mammalian muscles, affects renal sympathetic nerve activity (RSNA) and blood pressure (BP) in anesthetized rats. In the present study, using urethane-anesthetized rats, we examined the dose-dependent effects of intravenous (IV) injection of various doses of anserine, dipeptide of similar structure to L-carnosine, on RSNA, BP and heart rate (HR). We found that injection of a low dose of anserine (1 microg) significantly suppressed RSNA, BP and HR. Conversely, a high dose (1000 microg) of anserine significantly elevated RSNA, BP and HR. Pretreatment with lateral cerebral ventricular (LCV) injection of thioperamide, a histaminergic H(3)-receptor antagonist, eliminated the effects of a low dose of anserine on RSNA, BP and HR. LCV injection of diphenhydramine, a histaminergic H(1)-receptor antagonist, abolished the effects of a high dose of anserine on RSNA, BP and HR. These findings suggest that anserine affects RSNA, BP and HR in a dose-dependent manner, and that the histaminergic nerve may be involved in the dose-different effects of anserine in rats.

Differential neuroprotective effects of carnosine, anserine, and N-acetyl carnosine against permanent focal ischemia.

Carnosine (beta-alanyl-L-histidine) has been shown to exhibit neuroprotection in rodent models of cerebral ischemia. In the present study, we further characterized the effects of carnosine treatment in a mouse model of permanent focal cerebral ischemia and compared them with its related peptides anserine and N-acetylated carnosine. We also evaluated the efficacy of bestatin, a carnosinase inhibitor, in ameliorating ischemic brain damage. Permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery (pMCAO). Mice were subsequently randomly assigned to receive an intraperitoneal injection of vehicle (0.9% saline), carnosine, N-acetyl carnosine, anserine, bestatin alone, or bestatin with carnosine. Infarct size was examined using 2,3,5-triphenyltetrazolium chloride staining 1, 3, and 7 days following pMCAO, and neurological function was evaluated using an 18-point-based scale. Brain levels of carnosine were measured in treated mice using high-performance liquid chromatography 1 day following pMCAO. We demonstrated that treatment with carnosine, but not its analogues, was able to significantly reduce infarct volume and improve neurological function compared with those in vehicle-treated mice. These beneficial effects were maintained for 7 days post-pMCAO. In contrast, compared with the vehicle-treated group, bestatin-treated mice displayed an increase in the severity of ischemic lesion, which was prevented by the addition of carnosine. These new data further characterize the neuroprotective effects of carnosine and suggest that carnosine may be an attractive candidate for testing as a stroke therapy.

Safety evaluation of chicken breast extract containing carnosine and anserine.

Chicken breast extract (CBEX) is obtained via hot water extraction of chicken breast and contains among its primary constituents carnosine and anserine, which are histidine-containing dipeptides present in the muscle tissues of most vertebrate species. Dietary intake of CBEX has been previously shown to buffer hydrogen ions formed during high-intensity exercise in human skeletal muscle cells, thereby inhibiting a decrease in muscle cell pH and subsequent muscle fatigue. The objective of this paper is to report the results of safety studies completed on CBEX. CBEX was determined to have an oral LD(50) value of more than 6000 mg/kg body weight in rats. Gavage doses of 500 or 2000 mg CBEX/kg body weight/day administered to rats for 90 days produced no toxicologically significant, dose-related, differences between control and treated animals with respect to body weight gain, food consumption, behavioral effects, hematological and clinical chemistry parameters, absolute and relative organ weights, or gross and microscopic findings. In the presence or absence of metabolic activation, CBEX exerted no mutagenic activity in the Ames assay conducted in various strains of Salmonella typhimurium and Escherichia coli. The results of these studies support the safety of CBEX as a potential dietary source of carnosine and anserine.