A Patented Dietary Supplement (Hydroxy-Methyl-Butyrate, Carnosine, Magnesium, Butyrate, Lactoferrin) Is a Promising Therapeutic Target for Age-Related Sarcopenia through the Regulation of Gut Permeability: A Randomized Controlled Trial.

Adequate diet, physical activity, and dietary supplementation with muscle-targeted food for special medical purposes (FSMP) or dietary supplement (DS) are currently considered fundamental pillars in sarcopenia treatment. The aim of this study is to evaluate the effectiveness of a DS (containing hydroxy-methyl-butyrate, carnosine, and magnesium, for its action on muscle function and protein synthesis and butyrate and lactoferrin for their contribution to the regulation of gut permeability and antioxidant/anti-inflammation activity) on muscle mass (assessed by dual X-ray absorptiometry (DXA)), muscle function (by handgrip test, chair test, short physical performance battery (SPPB) test, and walking speed test), inflammation (tumor necrosis factor-alpha (TNF-a), C-reactive protein (CRP), and visceral adipose tissue (VAT)) and gut axis (by zonulin). A total of 59 participants (age 79.7 ± 4.8 years, body mass index 20.99 ± 2.12 kg/m2) were enrolled and randomly assigned to intervention (n = 30) or placebo (n = 28). The skeletal muscle index (SMI) significantly improved in the supplemented group compared to the placebo one, +1.02 (CI 95%: -0.77; 1.26), p = 0.001; a significant reduction in VAT was observed in the intervention group, -70.91 g (-13.13; -4.70), p = 0.036. Regarding muscle function, all the tests significantly improved (p = 0.001) in the supplemented group compared to the placebo one. CRP, zonulin, and TNF-alpha significantly decreased (p = 0.001) in intervention, compared to placebo, -0.74 mg/dL (CI 95%: -1.30; -0.18), -0.30 ng/mL (CI 95%: -0.37; -0.23), -6.45 pg/mL (CI 95%: -8.71; -4.18), respectively. This DS improves muscle mass and function, and the gut muscle has emerged as a new intervention target for sarcopenia.

Immobilized Dipeptidase in Manganese Ion-Loaded Polyethylenimine-Induced Calcium Phosphate Nanocrystals for Carnosine Synthesis.

Carnosine is a natural bioactive dipeptide with important physiological functions widely used in food and medicine. Dipeptidase (PepD) from Serratia marcescens can catalyze the reverse hydrolytic reaction of ß-alanine with l-histidine to synthesize carnosine in the presence of Mn2+. However, it remains challenging to practice carnosine biosynthesis due to the low activity and high cost of the enzyme. Therefore, the development of biocatalysts with high activity and stability is of significance for carnosine synthesis. Here, we proposed to chelate Mn2+ to polyethylenimine (PEI) that induced rapid formation of calcium phosphate nanocrystals (CaP), and Mn-PEI@CaP was used for PepD immobilization via electrostatic interaction. Mn-PEI@CaP as the carrier enhanced the stability of the immobilized enzyme. Moreover, Mn2+ loaded in the carrier acted as an in situ activator of the immobilized PepD for facilitating the biocatalytic process of carnosine synthesis. The as-prepared immobilized enzyme (PepD-Mn-PEI@CaP) kept similar activity with free PepD plus Mn2+ (activity recovery, 102.5%), while exhibiting elevated thermal stability and pH tolerance. Moreover, it exhibited about two times faster carnosine synthesis than the free PepD system. PepD-Mn-PEI@CaP retained 86.8% of the original activity after eight cycles of batch catalysis without the addition of free Mn2+ ions during multiple cycles. This work provides a new strategy for the co-immobilization of PepD and Mn2+, which greatly improves the operability of the biocatalysis and demonstrates the potential of the immobilized PepD system for efficient carnosine synthesis.

Enhancement of subunit vaccine delivery with zinc-carnosine coordination polymer through the addition of mannan.

Vaccines represent a pivotal health advancement for preventing infection. However, because carrier systems with repeated administration can invoke carrier-targeted immune responses that diminish subsequent immune responses (e.g., PEG antibodies), there is a continual need to develop novel vaccine platforms. Zinc carnosine microparticles (ZnCar MPs), which are composed of a one-dimensional coordination polymer formed between carnosine and the metal ion zinc, have exhibited efficacy in inducing an immune response against influenza. However, ZnCar MPs' limited suspendability hinders clinical application. In this study, we address this issue by mixing mannan, a polysaccharide derived from yeast, with ZnCar MPs. We show that the addition of mannan increases the suspendability of this promising vaccine formulation. Additionally, since mannan is an adjuvant, we illustrate that the addition of mannan increases the antibody response and T cell response when mixed with ZnCar MPs. Mice vaccinated with mannan + OVA/ZnCar MPs had elevated serum IgG and IgG1 levels in comparison to vaccination without mannan. Moreover, in the mannan + OVA/ZnCar MPs vaccinated group, mucosal washes demonstrated increased IgG, IgG1, and IgG2c titers, and antigen recall assays showed enhanced IFN-γ production in response to MHC-I and MHC-II immunodominant peptide restimulation, compared to the vaccination without mannan. These findings suggest that the use of mannan mixed with ZnCar MPs holds potential for subunit vaccination and its improved suspendability further promotes clinical translation.

Comparative evaluation of different modalities for measuring in vivo carnosine levels.

Carnosine is an endogenous di-peptide (ß-alanine -L- histidine) involved in maintaining tissue homeostasis. It is most abundant in skeletal muscle where its concentration has been determined in biopsy samples using tandem mass spectrometry (MS-MS). Carnosine levels can also be assessed in intact leg muscles by proton magnetic resonance spectroscopy (1H-MRS) or in blood and urine samples using mass spectrometry. Nevertheless, it remains uncertain how carnosine levels from these distinct compartments are correlated with each other when measured in the same individual. Furthermore, it is unclear which measurement modality might be most suitable for large-scale clinical studies. Hence, in 31 healthy volunteers, we assessed carnosine levels in skeletal muscle, via 1H-MRS, and in erythrocytes and urine by MS-MS. While muscle carnosine levels were higher in males (C2 peak, p = 0.010; C4 peak, p = 0.018), there was no sex-associated difference in urinary (p = 0.433) or erythrocyte (p = 0.858) levels. In a linear regression model adjusted for age, sex, race, and diet, there was a positive association between erythrocyte and urinary carnosine. However, no association was observed between 1H-MRS and erythrocytes or urinary measures. In the relationship between muscle versus urinary and erythrocyte measures, females had a positive association, while males did not show any association. We also found that 1H-MRS measures were highly sensitive to location of measurement. Thus, it is uncertain whether 1H-MRS can accurately and reliably predict endogenous carnosine levels. In contrast, urinary and erythrocyte carnosine measures may be stable and in greater synchrony, and given financial and logistical concerns, may be a feasible alternative for large-scale clinical studies.

Carnosine facilitates lysosomal release of inhibitors of T cell surveillance.

Cancer metabolism produces large fluxes of lactate and H+, which are extruded by membrane transporters. However, H+ production and extrusion must be coupled by diffusion, facilitated by mobile buffers. Yan et al. propose that carnosine, generated by CARNS2, provides this mobile buffering and enables lysosomal functions that block T cell surveillance.

Magnetic Lipid-Based hybrid nanosystems: A combined stimuli- responsive nanocarriers for enriched chemotherapeutic potential of L-carnosine in induced breast Ehrlich ascites tumor model.

Magnetic Lipid-Based Hybrid Nanosystems (M-LCNPs) is a novel nanoplatform that can respond to magnetic stimulus and are designed for delivering L-carnosine (CN), a challenging dipeptide employed in the treatment of breast cancer. CN exhibits considerable water solubility and undergoes in-vivo degradation, hence restricting its application. Consequently, it is anticipated that the developed M-LCNPs will enhance the effectiveness of CN. To ensure the physical stability of MNPs, they were initially coated with a mixture of oleic acid and oleylamine before being included in pegylated liquid crystalline nanoparticles (PLCNPs). The proposed M-LCNPs exhibited promising in-vitro characteristics, notably a small particle size (143.5 nm ± 1.25) and a high zeta potential (-39.5 mV ± 1.54), together with superparamagnetic behavior. The in-vitro release profile exhibited a prolonged release pattern. The IC50 values of M-LCNPs were 1.57 and 1.59 times lower than these of the CN solution after 24 and 48 hours, respectively. Female BALB/C female mice with an induced breast cancer (Ehrlich Ascites tumor [EAT] model) were used to study the influence of an external magnetic field on the chemotherapeutic activity and toxicity of CN loaded in the developed M-LCNPs. Stimuli-responsive M-LCNPs exhibited no apparent systemic toxicity in addition to enhanced chemotherapeutic efficacy compared to nontargeted M-LCNPs and CN solution, as evidenced by a reduction of % tumor growth (11.7%), VEGF levels (22.95 pg/g tissue), and cyclin D1 levels (27.61 ng/g tissue), and an increase in caspase-3 level (28.9 ng/g tissue). Ultimately, the developed stimuli-responsive CN loaded M-LCNPs presented a promising nanoplatform for breast cancer therapy.

Genome-wide association studies of anserine and carnosine contents in the breast meat of Korean native chickens.

Histidine-containing dipeptides (HCDs), such as anserine and carnosine, are enormously beneficial to human health and contribute to the meat flavor in chickens. Meat quality traits, including flavor, are polygenic traits with medium to high heritability. Polygenic traits can be improved through a better understanding of their genetic mechanisms. Genome-wide association studies (GWAS) constitute an effective genomic tool to identify the significant single-nucleotide polymorphisms (SNPs) and potential candidate genes related to various traits of interest in chickens. This study identified potential candidate genes influencing the anserine and carnosine contents in chicken meat through GWAS. We performed GWAS of anserine and carnosine using the Illumina chicken 60K SNP chip (Illumina Inc., San Diego, CA) in 637 Korean native chicken-red-brown line (KNC-R) birds consisting of 228 males and 409 females. The contents of anserine and carnosine in breast meat of KNC-R chickens were investigated. The mean value of the anserine and carnosine are 29.12 mM/g and 10.69 mM/g respectively. The genomic heritabilities were moderate (0.24) for anserine and high (0.43) for carnosine contents. Four and nine SNPs were significantly (P < 0.05) associated with anserine and carnosine, respectively. Based on the GWAS result, the 30.6 to 31.9 Mb region on chicken chromosome 7 was commonly associated with both anserine and carnosine. Through the functional annotation analysis, we identified HNMT and HNMT-like genes as potential candidate genes associated with both anserine and carnosine. The results presented here will contribute to the ongoing improvement of meat quality to satisfy current consumer demands, which are based on healthier, better-flavored, and higher-quality chicken meat.

Quantitative proteomics study of carnosine effect in an animal model of Western diet-induced nonalcoholic fatty liver disease.

The nonalcoholic fatty liver disease (NAFLD), which is closely related to westernized dietary (WD) patterns, displays a rising epidemiological and economic burden. Since there is no pharmacological therapy approved for this disease, mechanistic studies are warranted. In this work, we investigated the action of carnosine (CAR), a natural dipeptide with several protection roles against oxidative stress in the liver of NAFLD rats. NAFLD was induced by WD-rich sugars and fat, verifying the histological evidence of steatosis. As intraperitoneal administration of CAR reversed liver steatosis, the protein profiles of NAFLD liver and CAR NAFLD liver were evaluated by label-free proteomics approach. A total of 2531 proteins were identified and the 230 and 276 were significantly up- and downregulated, respectively, by CAR treatment of NAFLD rats and involved in fundamental pathways such as oxidative stress and lipid metabolism. Perilipin 2 and apolipoprotein E, components of the plasma membrane of vesicle, resulted in highly downregulated in the CAR-treated NAFLD liver. The advanced bioanalytical approach demonstrated the efficacy of CAR in overcoming the main symptoms of NAFLD, ameliorating the steatosis in the liver.

The effects of residual dipolar coupling on carnosine in proton muscle spectra.

Carnosine, an MR-visible dipeptide in human muscle, is well characterized by two peaks at ~8 and ~7 ppm from C2 and C4 imidazole protons. Like creatine and other metabolites, carnosine is subject to residual dipolar coupling in the anisotropic environment of muscle fibers, but the effects have not been studied extensively. Single-voxel TE 30-32 PRESS spectra from three different 3T studies were acquired from gastrocnemius medialis and soleus muscles in the human lower leg. In these studies, carnosine T2 values were measured, and spectra were obtained at three different foot angles. LCModel was used to fit the carnosine peaks with a basis set that was generated using shaped RF pulses and included a range of dipolar couplings affecting the C4 peak. A seven-parameter analytic expression was used to fit the CH2 doublets of creatine. It incorporated an optimized "effective TE" value to model the effect of shaped RF pulses. The fits confirm that the triplet C4 peak of carnosine is dipolar coupled to a pair of CH2 protons, with no need to include a contribution from a separate pool of freely rotating uncoupled carnosine. Moreover, the couplings experienced by carnosine C4 protons and creatine CH2 protons are strongly correlated (R2 = 0.88, P<0.001), exhibiting a similar 3cos2 θ - 1 dependence on the angle θ between fiber orientation and B0. T2 values for the singlet C2 peak of gastrocnemius carnosine are inversely proportional to the C4 dipolar coupling strength (R2 = 0.97, P < 0.001), which in turn is a function of foot orientation. This dependence indicates that careful positioning of the foot while acquiring lower leg muscle spectra is important to obtain reproducible carnosine concentrations. As proton magnetic resonance spectroscopy of carnosine is currently used to non-invasively estimate the muscle fiber typology, these results have important implications in sport science.

Carnosine supplementation improves glucose control in adults with pre-diabetes and type 2 diabetes: A randomised controlled trial.

BACKGROUND AND AIMS: Type 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions. METHODS AND RESULTS: In this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test. Secondary outcomes included body composition analysis by dual energy x-ray absorptiometry (DEXA), calf muscle density by pQCT, and anthropometry. Carnosine supplementation decreased blood glucose at 90 min (-1.31 mmol/L; p = 0.02) and 120 min (-1.60 mmol/L, p = 0.02) and total glucose area under the curve (-3.30 mmol/L; p = 0.04) following an oral glucose tolerance test. There were no additional changes in secondary outcomes. The carnosine group results remained significant before and after adjustment for age, sex, and change in weight (all>0.05), and in further sensitivity analyses accounting for missing data. There were no significant changes in insulin levels. CONCLUSION: This study provides preliminary support for larger trials evaluating carnosine as a potential treatment for prediabetes and the initial stages of T2DM. Likely mechanisms may include changes to hepatic glucose output explaining the observed reduction in blood glucose without changes in insulin secretion following carnosine supplementation.

Carnosine regulation of intracellular pH homeostasis promotes lysosome-dependent tumor immunoevasion.

Tumor cells and surrounding immune cells undergo metabolic reprogramming, leading to an acidic tumor microenvironment. However, it is unclear how tumor cells adapt to this acidic stress during tumor progression. Here we show that carnosine, a mobile buffering metabolite that accumulates under hypoxia in tumor cells, regulates intracellular pH homeostasis and drives lysosome-dependent tumor immune evasion. A previously unrecognized isoform of carnosine synthase, CARNS2, promotes carnosine synthesis under hypoxia. Carnosine maintains intracellular pH (pHi) homeostasis by functioning as a mobile proton carrier to accelerate cytosolic H+ mobility and release, which in turn controls lysosomal subcellular distribution, acidification and activity. Furthermore, by maintaining lysosomal activity, carnosine facilitates nuclear transcription factor X-box binding 1 (NFX1) degradation, triggering galectin-9 and T-cell-mediated immune escape and tumorigenesis. These findings indicate an unconventional mechanism for pHi regulation in cancer cells and demonstrate how lysosome contributes to immune evasion, thus providing a basis for development of combined therapeutic strategies against hepatocellular carcinoma that exploit disrupted pHi homeostasis with immune checkpoint blockade.

Effects of in ovo injection of the L-carnosine on physiological indexes of neonatal broiler chicken.

The objective of the present investigation was to ascertain the impact of in ovo administration of L-carnosine on physiological indicators in neonatal broiler chickens. A total of 280 viable broiler eggs were allocated to 7 distinct groups: control, Sham in ovo injection of sterile water on d 7 of incubation. Groups 3 and 4 were subjected to in ovo injections of L-carnosine (25 and 50 µg) on d 7 of incubation. Group 5, functioning as a sham in ovo, received an injection of sterile water on d 18 of incubation. Groups 6 and 7 were in ovo injected with L-carnosine (25 and 50 µg) on d 18 of incubation. All eggs were subjected to incubation, and the hatching rate and body weight were measured post-hatch. Subsequently, blood samples were collected, and the levels of biochemical constituents in the serum were determined. Based on the outcomes, the administration of L-carnosine (50 µg) on d 7 of incubation led to a significant increase in post-hatch body weight compared to the control group (P < 0.05). The in ovo injection of L-carnosine (25 and 50 µg) on d 7 and 18 of incubation resulted in a significant decrease in the levels of serum glucose, triglyceride (TG), low-density lipoprotein (LDL), phosphorus (P), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transaminase (ALT) in the newly hatched chickens (P < 0.05). Furthermore, the in-ovo injection of L-carnosine (25 and 50 µg) on d 7 and 18 of incubation led to a significant increase in the levels of serum high-density lipoprotein (HDL), calcium, and total protein (TP) in the newly hatched chickens (P < 0.05). Nonetheless, L-carnosine did not have a significant effect on the levels of serum IgY and IgA in the newly hatched chickens (P > 0.05). These findings indicate that the in ovo administration of L-carnosine yielded favorable outcomes in neonatal broiler chickens.

Unlocking the Molecular Variations of a Micron-Scale Amyloid Plaque in an Early Stage Alzheimer's Disease by a Cellular-Resolution Mass Spectrometry Imaging Platform.

Uncovering the molecular changes at the site where Aß is deposited plays a critical role in advancing the diagnosis and treatment of Alzheimer's disease. However, there is currently a lack of a suitable label-free imaging method with a high spatial resolution for brain tissue analysis. In this study, we propose a modified desorption electrospray ionization (DESI) mass spectrometry imaging (MSI) method, called segmented temperature-controlled DESI (STC-DESI), to achieve high-resolution and high-sensitivity spatial metabolomics observation by precisely controlling desorption and ionization temperatures. By concentrating the spray plume and accelerating solvent evaporation at different temperatures, we achieved an impressive spatial resolution of 20 µm that enables direct observation of the heterogeneity around a single cell or an individual Aß plaque and an exciting sensitivity that allows a variety of low-abundance metabolites and less ionizable neutral lipids to be detected. We applied this STC-DESI method to analyze the brains of transgenic AD mice and identified molecular changes associated with individual Aß aggregates. More importantly, our study provides the first evidence that carnosine is significantly depleted and 5-caffeoylquinic acid (5-CQA) levels rise sharply around Aß deposits. These observations highlight the potential of carnosine as a sensitive molecular probe for clinical magnetic resonance imaging diagnosis and the potential of 5-CQA as an efficient therapeutic strategy for Aß clearance in the early AD stage. Overall, our findings demonstrate the effectiveness of our STC-DESI method and shed light on the potential roles of these molecules in AD pathology, specifically in cellular endocytosis, gray matter network disruption, and paravascular Aß clearance.

The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review.

BACKGROUND/IMPORTANCE: Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases. OBJECTIVE: This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults. EVIDENCE REVIEW: The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non-pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence. FINDINGS: Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy-induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS-I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-l-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), l-carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha-lipoic acid (5 studies), vitamin B12 (3), acetyl-l-carnitine (3), vitamin E (1), vitamin D (2), and a low-fat plant-based diet (1). Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies. CONCLUSIONS: Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings.

Anticancer actions of carnosine in cellular models of prostate cancer.

Treatments for organ-confined prostate cancer include external beam radiation therapy, radical prostatectomy, radiotherapy/brachytherapy, cryoablation and high-intensity focused ultrasound. None of these are cancer-specific and are commonly accompanied by side effects, including urinary incontinence and erectile dysfunction. Moreover, subsequent surgical treatments following biochemical recurrence after these interventions are either limited or affected by the scarring present in the surrounding tissue. Carnosine (ß-alanyl-L-histidine) is a histidine-containing naturally occurring dipeptide which has been shown to have an anti-tumorigenic role without any detrimental effect on healthy cells; however, its effect on prostate cancer cells has never been investigated. In this study, we investigated the effect of carnosine on cell proliferation and metabolism in both a primary cultured androgen-resistant human prostate cancer cell line, PC346Flu1 and murine TRAMP-C1 cells. Our results show that carnosine has a significant dose-dependent inhibitory effect in vitro on the proliferation of both human (PC346Flu1) and murine (TRAMP-C1) prostate cancer cells, which was confirmed in 3D-models of the same cells. Carnosine was also shown to decrease adenosine triphosphate content and reactive species which might have been caused in part by the increase in SIRT3 also shown after carnosine treatment. These encouraging results support the need for further human in vivo work to determine the potential use of carnosine, either alone or, most likely, as an adjunct therapy to surgical or other conventional treatments.

Catechol chitosan coated dual-loaded liposomes based on oxidation and saccharification mechanisms for enhancing skin anti-aging effects.

Skin aging has become a major urgent problem to be solved. Evidence reveals that oxidation and glycosylation are two dominant inducements of aging. Resveratrol (RES) with outstanding anti-oxidant effect and carnosine (CAR) with superb anti-glycation property were selected as two model drugs to evaluate the feasibility of their synergistic anti-aging effect. RES and CAR at the most desired mass ratio, supplying the most superior synergistic anti-aging effects were further encapsulated in liposomes (LP), which were separately coated with chitosan (CS) and catechol chitosan (Cat-CS) to increase the transdermal penetration. Their anti-aging efficacy was explored in human skin fibroblast (HSF) and human immortalized keratinocytes (HaCaT) cells, as well as the back skin of guinea pigs. Herein, RES and CAR at the mass ratio of 2:1 exhibited the most ideal synergistic anti-aging effect. The constructed liposomes have been shown to possess excellent fundamental properties and sustained-release properties. The aging-related indicator levels in the two cells and guinea pigs were obviously improved for the RES + CAR@Cat-CS-LP group. Additionally, skin appearance, tissue morphology, and collagen content were visibly improved, indicating its perfect anti-aging effect. In conclusion, RES + CAR@Cat-CS-LP is expected to be exploited as a potential anti-aging drug delivery system.

Effects of carnosine supplementation on markers for the pathophysiological development of metabolic dysfunction-associated steatotic liver disease in a diet-induced model.

Consumption of diets high in sugar and fat is related to the development of Metabolic dysfunction-associated steatotic liver disease (MASLD). Carnosine (CAR) is a dipeptide with antioxidant and anti-inflammatory action and has been studied for treating diseases. This work aimed to evaluate the effects of CAR on diet-induced MASLD in rats. Male Wistar rats were distributed into 2 groups (17 weeks): normocaloric (Co, n = 12), and hypercaloric diet rich in lipids and simple carbohydrates (MASLD, n = 12). After, the animals were redistributed to begin the treatment with CAR (4 weeks): Co (n = 6), Co + CAR (n = 6), MASLD (n = 6), and MASLD + CAR (n = 6), administered intraperitoneally (250 mg/kg). Evaluations included nutritional, hormonal and metabolic parameters; hepatic steatosis, inflammatory and oxidative markers. MASLD group had a higher adiposity index, systolic blood pressure, glucose, plasma and liver triglycerides and cholesterol, insulin, hepatic steatosis, oxidative markers, and lower PPAR-α (Peroxisome Proliferator-activated receptor α), compared to the Co. CAR attenuated plasma and hepatic triglyceride and cholesterol levels, hepatic steatosis, CD68+ macrophages, and hepatic oxidative markers, in addition to increasing HDL cholesterol levels and PPAR-α, compared to the untreated MASLD group. CAR acts in importants pathophysiological processes of MASLD and may be a therapeutic compound to control the disease.

Human carnosinases: A brief history, medicinal relevance, and in silico analyses.

Carnosine, an endogenous dipeptide, has been found to have a plethora of medicinal properties, such as antioxidant, antiageing, and chelating effects, but with one downside: a short half-life. Carnosinases and two hydrolytic enzymes, which remain enigmatic, are responsible for these features. Hence, here we emphasize why research is valuable for better understanding crucial concepts like ageing, neurodegradation, and cancerogenesis, given that inhibition of carnosinases might significantly prolong carnosine bioavailability and allow its further use in medicine. Herein, we explore the literature regarding carnosinases and present a short in silico analysis aimed at elucidating the possible recognition pattern between CN1 and its ligands.

Dual effects of dietary carnosine during in vitro digestion of a Western meal model with added ascorbic acid.

The beneficial role of carnosine during in vitro digestion of meat was previously demonstrated, and it was hypothesized that such benefits could also be obtained in a meal system. The current study, therefore, assessed carnosine effects on markers of lipid and protein oxidation and of advanced glycation end products (AGEs) during gastric and duodenal in vitro digestion of a burger meal model. The model included intrinsic (low) and enhanced (medium and high) carnosine levels in a mix of pork mince and bread, with or without ascorbic acid (AA) and/or fructose as anti- and prooxidants, respectively. In the presence of either AA or fructose, a carnosine prooxidative potential during digestion was observed at the medium carnosine level depending on markers and digestive phases. However, free carnosine found at the high carnosine level exerted a protective effect reducing the formation of 4-hydroxynonenal in the gastric phase and glyoxal in both the gastric and duodenal phases. Dual effects of carnosine are likely concentration related, whereby at the medium level, free radical production increases through carnosine's ferric-reducing capacity, but there is insufficient quantity to reduce the resulting oxidation, while at the higher carnosine level some decreases in oxidation are observed. In order to obtain carnosine benefits during meal digestion, these findings demonstrate that consideration must be given to the amount and nature of other anti- and prooxidants present and any potential interactions. PRACTICAL APPLICATION: Carnosine, a natural compound in meat, is a multifunctional and beneficial molecule for health. However, both pro- and antioxidative effects of carnosine were observed during digestion of a model burger meal when ascorbic acid was included at a supplemental level. Therefore, to obtain benefits of dietary carnosine during digestion of a meal, consideration needs to be given to the amount and nature of all anti- and prooxidants present and any potential interactions.