1. L-carnosine and its Derivatives as New Therapeutic Agents for the Prevention and Treatment of Vascular Complications of Diabetes
Stefano Menini, Giuseppe Pugliese, Claudia Blasetti Fantauzzi, Carla Iacobini Curr Med Chem . 2020;27(11):1744-1763. doi: 10.2174/0929867326666190711102718.
Vascular complications are among the most serious manifestations of diabetes. Atherosclerosis is the main cause of reduced life quality and expectancy in diabetics, whereas diabetic nephropathy and retinopathy are the most common causes of end-stage renal disease and blindness. An effective therapeutic approach to prevent vascular complications should counteract the mechanisms of injury. Among them, the toxic effects of Advanced Glycation (AGEs) and Lipoxidation (ALEs) end-products are well-recognized contributors to these sequelae. L-carnosine (β-alanyl-Lhistidine) acts as a quencher of the AGE/ALE precursors Reactive Carbonyl Species (RCS), which are highly reactive aldehydes derived from oxidative and non-oxidative modifications of sugars and lipids. Consistently, L-carnosine was found to be effective in several disease models in which glyco/lipoxidation plays a central pathogenic role. Unfortunately, in humans, L-carnosine is rapidly inactivated by serum carnosinase. Therefore, the search for carnosinase-resistant derivatives of Lcarnosine represents a suitable strategy against carbonyl stress-dependent disorders, particularly diabetic vascular complications. In this review, we present and discuss available data on the efficacy of L-carnosine and its derivatives in preventing vascular complications in rodent models of diabetes and metabolic syndrome. We also discuss genetic findings providing evidence for the involvement of the carnosinase/L-carnosine system in the risk of developing diabetic nephropathy and for preferring the use of carnosinase-resistant compounds in human disease. The availability of therapeutic strategies capable to prevent both long-term glucose toxicity, resulting from insufficient glucoselowering therapy, and lipotoxicity may help reduce the clinical and economic burden of vascular complications of diabetes and related metabolic disorders.
2. The effects of l-Carnosine on development of metabolic syndrome in rats
Osama Y Alshogran, Nour A Al-Sawalha, Mofleh S Awawdeh, Basima A Almomani Life Sci . 2019 Nov 15;237:116905. doi: 10.1016/j.lfs.2019.116905.
Aims:The prevalence of metabolic syndrome (MetS) is increasing in several countries. The MetS is characterized by the occurrence of at least three of the following risk factors: decreased high-density lipoprotein cholesterol, increased blood pressure, raised fasting blood glucose, elevated triglycerides, and abdominal obesity. There is a growing evidence of the role of l-carnosine in improving lipid profile and enhancement of the antioxidant activity. However, the effects of l-carnosine on development of MetS are unknown.Main methods:Male Wistar rats were randomly assigned to receive either; conventional diet (control), high-fat high-carbohydrate diet (HFHCD), l-carnosine and conventional diet (L-Car), or l-carnosine and high-fat high-carbohydrate diet (HFHCD and L-Car) for 16 weeks. Central obesity, systolic blood pressure, lipid profile, glucose hemostasis, levels of leptin and adiponectin were evaluated on week 16.Key findings:Rats that received HFHCD for 16 weeks showed MetS phenotype such as central obesity, increased blood pressure and glucose, as well as an altered lipid profile (P < 0.05). l-Carnosine supplementation to MetS rats significantly reduced abdominal obesity, blood pressure and glucose, and normalized total cholesterol and low density lipoprotein cholesterol levels (P < 0.05). Insulin, leptin and adiponectin concentrations were not affected by l-Carnosine (P > 0.05).Significance:l-carnosine has beneficial effects on ameliorating the manifestations of MetS in rats.
3. L-Carnosine combination therapy for major depressive disorder: A randomized, double-blind, placebo-controlled trial
Ali Aqamolaei, Erfan Sahebolzamani, Shahin Akhondzadeh, Salomeh Ghaffari, Elham Shirazi, Behin Araminia, Mehrdad Eftekhar Ardebili, Behnam Shariati, Seyyed Hosein Mortazavi, Sina Naderi, Mohammadreza Shalbafan, Amirhosein Mortezaei J Affect Disord . 2020 Apr 15;267:131-136. doi: 10.1016/j.jad.2020.02.020.
Background:Evidence for antidepressant effects of L-Carnosine was shown in some experimental studies. In this study we tried to evaluate the efficacy and tolerability of L-Carnosine combination therapy in treatment of patients with major depressive disorder (MDD).Methods:Fifty-eight patients with MDD (DSM-V) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 400 mg twice daily L-Carnosine or placebo in addition to citalopram (maximum dosage of 40 mg/day) for six weeks in a randomized double-blind, and placebo-controlled study. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6.Results:Fifty-two patients completed the trial. General linear model repeated measure showed significant difference for time × treatment on HAM-D score [F = 3.17, df = 2.39, p-value = 0.03]. Significantly greater improvement was detected in HAM-D score of the L-Carnosine group compared with the placebo group from baseline to weeks 2, 4 and 6 [Ps = 0.013, 0.028 and 0.023; respectively]. Patients in the L-Carnosine group experienced significantly greater response and remission rate than the placebo group [Ps = 0.023 and 0.012; respectively]. There was no significant difference between the two groups in baseline parameters and frequency of side effects.Limitations:Short follow-up period and small population size were two important limitations of this study.Conclusions:L-Carnosine combination therapy with citalopram can effectively improve symptoms of patients with major depressive disorder. Rapid-onset antidepressant effects of L-Carnosine were also shown which need further investigation.
