Carnosine对Aβ_(25-35)诱发PC12细胞损伤的神经保护作用

目的 研究 Carnosine对 β淀粉样蛋白片段 (Aβ2 5- 3 5)诱发 PC1 2细胞损伤的神经保护作用。方法 将培养的 PC1 2细胞分为三组 :正常对照组、损伤组和保护组。损伤组用 Aβ2 5- 3 5处理细胞 ,保护组在用 Aβ2 5- 3 5处理前 30 min加入 Carnosine。使用细胞形态学方法、LDH法、MTT法观察 Carnosine的神经保护作用。结果 通过形态学方法 ,保护组细胞数显著比损伤组多 ,受损变圆的细胞数较少。保护组 LDH活性显著少于损伤组(P<0 .0 1 ) ;MTT显著高于损伤组 (P<0 .0 1 )。结论 Carnosine对 Aβ2 5- 3 5诱发 PC1 2细胞损伤有显著的保护作用。

Conformations of Carnosine in Aqueous Solutions by All-Atom Molecular Dynamics Simulations and 2D-NOSEY Spectrum

All-atom molecular simulations and two-dimensional nuclear overhauser effect spectrum have been used to study the conformations of carnosine in aqueous solution. Intramolecular distances, root-mean-square deviation, radius of gyration, and solvent-accessible surface are used to characterize the properties of the carnosine. Carnosine can shift between extended and folded states, but exists mostly in extended state in water. Its preference for extension in pure water has been proven by the 2D nuclear magnetic resonance （NMR） experiment. The NMR experimental results are consistent with the molecular dynamics simulations.

Carnosine and N-Acetylcarnosine Induce Inhibition of UVB Erythema in Human Skin

Background: Carnosine is a low molecular weight water soluble biological dipeptide, composed of alanine and histidine, present in a levorotatory form in mammalian tissues. Interesting activities are related to the detoxification from free radical species and byproducts of membrane lipids peroxidation. Objectives: The aim of the present study was to evaluate the photoprotective properties of carnosine and acetylated carnosine when applied to human skin. Materials and methods: Carnosine and N-acetylcarnosine at 0.5% solution in water were applied before and after UVB irradiation in twenty healthy volunteers with phototype 2 or 3. 9 patients were males and 11 females, 25 to 46 years of age. None of the patients had a positive case history for photodermatoses or had received any sun exposure. The minimal erithemal dose (MED) for UVB was determined before the study with a UVB Philips TL12 lamp with a radiance of 4 mW/cm2 and a 290 - 320 nm emission spectrum. Results: Carnosine solution obtained 3.6% reduction of erythema (compared to MED) and N-acetylcarnosine 7.3% reduction. Conclusions: An antioxidant capacity of N-acetylcarnosine and carnosine was shown, probably more significant with vehicles improving skin penetration of the substances through skin barrier. N-acetylcarnosine represents an interesting hydrophilic antioxidant for dermatological preparations.

Protective effects of carnosine on white matter damage induced by chronic cerebral hypoperfusion

Carnosine is a dipeptide that scavenges free radicals, inhibits infammation in the central nervous system, and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions. Therefore, we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury. White matter damage was induced by right unilateral common carotid artery occlusion in mice. The animals were treated with 200, 500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury. Then, 37 days later, Klfiver-Barrera staining, toluidine blue staining and immunofluorescence stain- ing were performed. Carnosine （200, 500 mg/kg） substantially reduced damage to the white matter in the corpus callosum, internal capsule and optic tract, and it rescued expression of myelin basic protein, and alleviated the loss of oligodendrocytes. However, carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses. These findings show that carnosine, at a particular dose range, protects against white matter damage caused by chronic cerebral ischemia in mice, likely by reducing oligodendroglial cell loss.

Carnosine concentration and expression profiles of carnosine related genes in Mytilus after beta-alanine injection

Carnosine and its analogues are histidine-containing dipeptides(HCDs)playing diverse functions in vertebrates.However,the distribution and the metabolism of carnosine in invertebrates are still unknown.In this study,Mytilus coruscus,a shellfish with important economic value in China,was selected for the investigation of HCD content and the expression profiling of carnosine-related genes in various mussel tissues.Quantification of HCD by amino acids analyzer revealed a low concentration of anserine in muscular tissues in Mytilus,indicating the presence of HCD even in an invertebrate.mRNA expression of five carnosine metabolic-related genes was profiled in various tissues,and the results highlighted the relative higher expression level of these genes in muscular tissues.Considering the fact that beta-alanine supplementation can increase the HCD content in vertebrates,a beta-alanine injection was performed and the changes of HCD concentration and the mRNA expression of carnosine related genes were investigated in five mussel tissues.The results revealed the increase of HCD concentration,as well as the up-regulated expression level of related genes,in tested tissues of beta-alanine injected mussels.Transcriptomic analysis for the whole soft tissue of mussel before and after beta-alanine injection were performed,and 3569 differential expression genes(DEGs)were identified in the beta-alanine injected group when compared to their expression levels in the control.These data indicated the complex eff ects of betaalanine on M.coruscus metabolism,and those DEGs enriched in pathways of cancers,muscle contraction,and tyrosine metabolism highlighted the possible functions of beta-alanine in cell proliferation,sports,and melanogenesis,respectively.

Nickel-Carnosine complex:A new carrier for enzymes immobilization by affinity adsorption

Immobilization is an effective method to promote the application of enzyme industry for improving the stability and realizing recovery of enzyme.To some extent,the performance of immobilized enzyme depends on the choice of carrier material.Therefore,the development of new carrier materials has been one of the key issues concerned by enzyme immobilization researchers.In this work,a novel organic–inorganic hybrid material,nickel-carnosine complex(NiCar),was synthesized for the first time by solvothermal method.The obtained NiCar exhibits spherical morphology,hierarchical porosity and abundant unsaturated coordination nickel ions,which provide excellent anchoring sites for the immobilization of proteins.His-tagged organophosphate-degrading enzyme(Opd A)and x-transaminase(ω-TA)were used as model enzymes to evaluate the performance of NiCar as a carrier.By a simple adsorption process,the enzyme molecules can be fixed on the particles of NiCar,and the stability and reusability are significantly improved.The analysis of protein adsorption on NiCar verified that the affinity adsorption between the imidazole functional group on the protein and the unsaturated coordination nickel ions on NiCar was the main force in the immobilization process,which provided an idea way for the development of new enzyme immobilization carriers.

Efficacy Study on the Anti-Aging Emulsion Containing Carnosine and Centella Asiatica Extract

A clinical study was conducted on the anti-aging effects of an emulsion containing carnosine and centella asiatica extract to provide a reference for the evaluation and development of anti-aging cosmetics.Sixty healthy females,aged 35~60,were divided into the test sample and placebo groups.Skin elasticity and wrinkles of the participants were analyzed before they used the emulsion and after they used it for 8 weeks.Instrument measurement results showed that after 8 weeks,skin elasticity and wrinkles in the members of the test sample group improved relative to those of the placebo group.Clinical effect assessment results showed that subjects did not experience adverse skin reactions,and their skin wrinkles showed improvement.Self-assessment results showed that the score of the total satisfaction of the test sample was 4.3,and 100%subjects are satisfied with the test sample.Emulsion containing carnosine and centella asiatica extract has a certain anti-aging effect.

Effects of carnosine on the evoked potentials in hippocampal CA1 region

Objective： To directly examine the effects ofcarnosine on neuronal excitation and inhibition in rat hippocampus in vivo. Methods： Artificial cerebrospinal fluid with carnosine was directly administrated over the exposed rat hippocampus. The changes of neuron activity in the CA1 region of hippocampus were evaluated by orthodromically- and antidromically-evoked potentials, as well as paired-pulse stimulation paradigm. Results： In both orthodromic and antidromic response potentials, carnosine transformed population spikes （PSs） with single spike into epileptiform multiple spikes. In addition, similar to the effect of 7-aminobutyric acidA （GABAA） antagonist picrotoxin, camosine decreased paired-pulse stimulating depression significantly. However, no significant change was observed in the spontaneous field potentials during the application of carnosine. Conclusion： The results indicate a disinhibition-induced excitation effect of carnosine on the CA1 pyramidal neurons. It provides important information against the application of carnosine as a potential anticonvulsant in clinical treatment.

The Effect of 4 Weeks of Strength Training and Beta-Alanine Supplementation on Anaerobic Power and Carnosine Level in Boxer Players

Purpose The objective of this study was to investigate the effect of 4 weeks of strength training with beta-alanine supple-mentation on anaerobic power and carnosine level in boxer players.Methods Eighteen male boxer players participated in this study,randomly divided into two homogeneous groups(strength training+beta-alanine and strength training+placebo groups).The study design was double-blind,parallel,and placebo-controlled.An anaerobic Wingate test was performed by athletes before and after the intervention period(4 weeks).Par-ticipants received 0.3 g/kg of body mass of the supplement(maltodextrin or beta-alanine)per day during the intervention.Participants were also evaluated for anaerobic power,serum level of carnosine,and blood lactate before and after 4 weeks.Results Average power in both groups was significantly increased compared with pre-intervention,but fatigue index was significantly decreased only after beta-alanine supplementation;however,there were no significant differences with either average power or fatigue index between the beta-alanine and placebo groups.There was no significant difference in the interaction between the groups and time,as well as no significant difference between groups for lactic acid.Carnosine level in both groups was significantly increased compared with pre-intervention.When changes in serum carnosine for the two groups were examined,statistical analysis showed a significant difference between the beta-alanine and placebo groups.Conclusion Four weeks of strength training accompanied by beta-alanine supplementation had a likely beneficial effect on boxer players'anaerobic performance and carnosine level.

Carnosine and crocin ameliorate oxidative stress in rats with rhabdomyolysis-induced acute kidney injury through upregulating HO-1 gene expression

We aimed to investigate whether carnosine(a natural dipeptide found in humans)and crocin(a natural product extracted from saffron and gardenia)can prevent the harmful effects of acute kidney injury(AKI)caused by glycerol-induced rhabdomyolysis with a focus on the role of the nuclear factor E2-related factor-2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.Thirty-six male Wistar rats were divided into 6 groups:3 of them received saline,carnosine,and crocin IP for 7 days and the other 3 groups received the same treatment in addition to a single IM injection of 50%glycerol(10 ml/kg,divided between the two limb muscles)on 8th day.All animals were sacrificed after 24 h of the IM injection.Blood samples,muscles,and kidneys were collected for further investigations.Rhabdomyolysis was evidenced by the histopathological alterations in muscle sections and increased levels of myoglobin in kidney tissue homogenate samples.Kidney injury was characterized by increased creatinine,kidney injury molecule-1,malondialdehyde,nitric oxide,and decreased catalase activity.The injury also increased inflammatory markers and histopathological alterations in kidney sections.All these effects were corrected by pretreatment with carnosine and crocin.Both agents could also elevate HO-1 gene expression.However,both agents failed to restore the declined Nrf2 expression in glycerol-treated groups.Carnosine and crocin can effectively prevent rhabdomyolysis-induced AKI in rats through augmenting gene expression of HO-1 and antioxidant system and suppressing the generation of reactive oxygen species,lipid peroxidation,and inflammatory response.

Progression of intervention-focused research for Gulf War illness

The Persian Gulf War of 1990 to 1991 involved the deployment of nearly 700,000 American troops to the Middle East.Deployment-related exposures to toxic substances such as pesticides,nerve agents,pyridostigmine bromide(PB),smoke from burning oil wells,and petrochemicals may have contributed to medical illness in as many as 250,000 of those American troops.The cluster of chronic symptoms,now referred to as Gulf War Illness(GWI),has been studied by many researchers over the past two decades.Although over$500 million has been spent on GWI research,to date,no cures or condition-specific treatments have been discovered,and the exact pathophysiology remains elusive.Using the 2007 National Institute of Health(NIH)Roadmap for Medical Research model as a reference framework,we reviewed studies of interventions involving GWI patients to assess the progress of treatment-related GWI research.All GWI clinical trial studies reviewed involved investigations of existing interventions that have shown efficacy in other diseases with analogous symptoms.After reviewing the published and ongoing registered clinical trials for cognitivebehavioral therapy,exercise therapy,acupuncture,coenzyme Q10(CoQ10),mifepristone,and carnosine in GWI patients,we identified only four treatments(cognitive-behavioral therapy,exercise therapy,CoQ10,and mifepristone)that have progressed beyond a phase II trial.We conclude that progress in the scientific study of therapies for GWI has not followed the NIH Roadmap for Medical Research model.Establishment of a standard case definition,prioritized GWI research funding for the characterization of the pathophysiology of the condition,and rapid replication and adaptation of early phase,single site clinical trials could substantially advance research progress and treatment discovery for this condition.