Background The pathophysiology of sensitive skin consists of an inflammatory reaction resulting from the abnormal penetration in the skin of potentially irritating substances, which occurs due to skin barrier dysfunction and changes in... more
Background The pathophysiology of sensitive skin consists of an inflammatory reaction resulting from the abnormal penetration in the skin of potentially irritating substances, which occurs due to skin barrier dysfunction and changes in the production of local neuromediators.Aims The therapeutic potential of l-carnosine and Rhodiola rosea, as antioxidant and neuromodulatory, respectively, leads us to investigate the effects of the R. rosea extract/l-carnosine–associated compound (RCAC) on sensitive skin alterations.Methods A double-blind comparative study was conducted on 124 volunteers with sensitive skin, who were selected by their reactivity to stinging test. Two randomized groups of 62 each received either a formulation containing 1% of RCAC or placebo, which was applied twice a day for 28 consecutive days. One perceptibility questionnaire was applied at the onset and at the end of the treatment to evaluate the subjective response to test product. Additionally, in vitro studies were performed to investigate RCAC neuroimmunomodulatory mechanisms.Results RCAC treatment produced in vivo protective effects in skin barrier function and a positive subjective response of sensitive skin volunteers. In vitro treatment promoted the release of proopiomelanocortin peptides and restored to normal the increased levels of neuropeptides and cytokines produced by keratinocytes exposed to ultraviolet radiation. Clinical effectiveness was measured by reduction of transepidermal water loss, positive perceptions of improvements in skin dryness and skin comfort sensation, and reduction of discomfort sensation after stinging test.Conclusions The protective effect of RCAC in skin barrier function and the positive response produced in human subjects with sensitive skin could be partially explained by our in vitro results showing a significant increase in opioid peptides release, an inhibitory effect on neuropeptides production, and modulation of cytokines production by keratinocytes under ultraviolet stress.
Insulin-like growth factor binding protein 1 (IGFBP1) is a member of the binding proteins for the insulin-like growth factors (IGF) with an important role in glucose homeostasis. Circulating IGFBP1 is derived essentially from the liver... more
Insulin-like growth factor binding protein 1 (IGFBP1) is a member of the binding proteins for the insulin-like growth factors (IGF) with an important role in glucose homeostasis. Circulating IGFBP1 is derived essentially from the liver where it is mainly regulated negatively by insulin. Carnosine, a natural antioxidant, has been shown to improve metabolic control in different animal models of diabetes but its mechanisms of action are still not completely unraveled. We therefore investigate the effect of carnosine treatment on the IGFBP1 regulation in db/db mice. Db/db mice and heterozygous non-diabetic mice received for 4 weeks regular water or water supplemented with carnosine. Igfbp1 mRNA expression in the liver was evaluated using qPCR and the protein levels in plasma by Western blot. Plasma IGF1 and insulin were analyzed using immunoassays. HepG2 cells were used to study the in vitro effect of carnosine on IGFBP1. The modulation of hypoxia inducible factor-1 alpha (HIF-1 alpha) ...
Whole rings of hamster jejunum and ileum were used to study the uptake of L-histidine (L-His) and beta-alanine (beta-Ala), the constituents of the dipeptide carnosine. The rate of uptake of L-His and beta-Ala (1 mM) was not significantly... more
Whole rings of hamster jejunum and ileum were used to study the uptake of L-histidine (L-His) and beta-alanine (beta-Ala), the constituents of the dipeptide carnosine. The rate of uptake of L-His and beta-Ala (1 mM) was not significantly different in the jejunum compared with the ileum. Results of total influx (2 min) of 0.5-100 mM L-His suggested that transport was by more than one pathway, and the contribution of nonmediated component was calculated to be 0.24 mumol X g-1 X 2 min-1 X mM-1 for both jejunum and ileum. The apparent affinity of L-His for a transporter was higher in the ileum (K iota, 8.0 mM) than the jejunum (Kt, 11.7 mM). Influx (2 min) of beta-Ala was found to be linearly related to substrate concentration over the range 0.5-100 mM. The Kd (rate constant for nonmediated uptake of beta-Ala) was 0.23 and 0.14 mumol X g-1 X 2 min-1 X mM-1 for jejunum and ileum, respectively. Steady-state (20-min) uptake of L-His was significantly higher in the ileum than jejunum at sub...
Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. The current paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for... more
Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. The current paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 cocrystallized with nCoV spike protein. Methods: First, the starting point was ACE2 inhibitors and their structure-activity relationship (SAR). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19. Parallel, at all stages, the authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 with nCoV spike protein. Results: Carnosine emerged as the best-known drug candidate to match ACE2 inhibitor structure. Preliminary docking was more optimal to ACE2 than the known typical angiotensin-converting enzyme 1 (ACE1) inhibitor (enalapril) and quite comparable to known or presumed ACE2 inhibitors. Viral spike protein elements binding to ACE2 were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the protein-protein structure, carnosine bound with higher affinity to two compared to the known ACE2 active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49. Conclusion: Carnosine has promising inhibitory interactions with host ACE2 and nCoV spike protein and hence could offer a potential mitigating effect against the current COVID-19 pandemic.
The purpose of this study was to determine the effects of beta-alanine supplementation and high-intensity interval training (HIIT) on electromyographic fatigue threshold (EMGFT) and efficiency of electrical activity (EEA). A total of 46... more
The purpose of this study was to determine the effects of beta-alanine supplementation and high-intensity interval training (HIIT) on electromyographic fatigue threshold (EMGFT) and efficiency of electrical activity (EEA). A total of 46 men completed four, 2-min work bouts on a cycle ergometer. Using bipolar surface electrodes, the EMG amplitude was averaged and plotted over the 2-min. The resulting slopes were used to calculate EMGFT and EEA. Following initial testing, all participants were randomly assigned to either placebo (PL; n = 18), beta-alanine (BA; n = 18) or control groups (CON; n = 10). Following randomization, participants engaged in 6 weeks of HIIT training. Significant improvements in EMGFT and EEA resulted for both training groups. In conclusion, HIIT appeared to be the primary stimulus effecting EMGFT or EEA, suggesting adaptations from HIIT may be more influential than increasing skeletal muscle carnosine levels on delaying fatigue in recreationally active men.
Biogenic amines (BAs) play significant roles in indicating human health or food quality. Aiming to simultaneously determine three structures (aliphatic, aromatic and heterocyclic) of underivatized BAs, we explored a simple and rapid... more
Biogenic amines (BAs) play significant roles in indicating human health or food quality. Aiming to simultaneously determine three structures (aliphatic, aromatic and heterocyclic) of underivatized BAs, we explored a simple and rapid capillary electrophoresis (CE) method only coupled with conventional UV detector for the separation of thirteen key BAs. The strategy is to choose a UV absorbing probe as co-ion in the background electrolyte (BGE), and different BAs could be characterized by positive or negative peaks according to the fact that their UV absorptivity coefficients at a certain wavelength are better or worse than that of the UV absorbing probe. After the detailed investigation of critical parameters as pH, the concentration of Imidazole (Im) and α-cyclodextrin (α-CD), the optimized BGE consisted of 12.0mmol/L Im as the UV probe and 10.0mmol/L α-CD as the additive (at pH 4.50 adjusted with acetic acid). With such condition, the targets of thirteen BAs were baseline separated...
Ageing of populations globally, coupled with the obesity epidemic, has resulted in the rising prevalence of chronic diseases including diabetes, cardiovascular diseases, cancers and neurodegenerative disorders. Prevention of risk factors... more
Ageing of populations globally, coupled with the obesity epidemic, has resulted in the rising prevalence of chronic diseases including diabetes, cardiovascular diseases, cancers and neurodegenerative disorders. Prevention of risk factors that contribute to these diseases is key in managing the global burden of chronic diseases. Recent studies suggest that carnosine, a dipeptide with anti-inflammatory, antioxidative and antiglycating properties may have a role in the prevention of chronic diseases; however, no previous reviews have examined the effects of carnosine and other histidine-containing peptides (HCDs) on chronic disease risk factors and outcomes. We aim to conduct a comprehensive systematic review to examine the effects of supplementation with carnosine and other HCDs on chronic disease risk factors and outcomes and to identify relevant knowledge gaps. Electronic databases including Medline, Cumulative Index of Nursing and Allied Health, Embase and all Evidence-Based Medici...
Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of L-histidine (His) attenuates OS in brain of HE animal models, but the underlying... more
Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of L-histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (β-alanyl-L-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the well documented anti-OS activity of His. Amino acids [His or Car (100 mg/kg)] were administrated 2 h before TAA (i.p., 300 mg/kg 3× in 24 h intervals) injection into Sprague-Dawley rats. The animals were thus tested for: (i) brain prefrontal cortex and blood contents of Car and His, (ii) amount of reactive oxygen species (ROS), total antioxidant capacity (TAC), GSSG/GSH ratio and thioredoxin reductase (TRx) activity, and (iii) behavioral changes (several models were used, i.e. tests for reflexes,...
Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. However, their exact function is not clear. The antioxidant activity of these compounds has been examined by... more
Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. However, their exact function is not clear. The antioxidant activity of these compounds has been examined by testing their peroxyl radical-trapping ability at physiological concentrations. Carnosine, homocarnosine, anserine, and other histidine derivatives all showed antioxidant activity. All of these compounds showing peroxyl radical-trapping activity were also electrochemically active as reducing agents in cyclic voltammetric measurements. Furthermore, carnosine inhibited the oxidative hydroxylation of deoxyguanosine induced by ascorbic acid and copper ions. Other roles of carnosine, such as chelation of metal ions, quenching of singlet oxygen, and binding of hydroperoxides, are also discussed. The data suggest a role for these histidine-related compounds as endogenous antioxidants in brain and muscle.