Abstract

Carnosine is an endogenous dipeptide whose oral administration has been found to prevent several oxidative based diseases including lung disease, type 2 diabetes and its micro and macrovascular complications, cardiovascular disorders, neurodegenerative and kidney disease. While it is generally accepted that the beneficial effects of carnosine are due to its antioxidant, anti-advanced glycation end product (AGE) and -advanced lipoxidation end product (ALE) and anti-inflammatory properties, the molecular mechanisms explaining such effects have not yet been clearly defined. Studies indicate that carnosine acts by a direct antioxidant mechanism and by sequestering reactive carbonyls (RCS), the byproducts of lipid and glucose oxidation, thus inhibiting AGE and ALE which are the reaction products of RCS with proteins. Moreover, carnosine has also been found to act indirectly by activating the Nrf2 transcription factor, a mechanism that would explain many of the effects evoked by this peptide such as anti-inflammatory, antioxidant, antiglycation and anti-carbonyl effects and taken together would explain its therapeutic effect. The present review reports and discusses the most recent studies on the molecular mechanisms of carnosine which need to be fully clarified before promoting carnosine and derivatives as therapeutic agents.

摘要

肌肽是一种内源性二肽，经口服给药可预防多种基于氧化的疾病，包括肺部疾病，2型糖尿病及其微血管和大血管并发症，心血管疾病，神经退行性疾病和肾脏疾病。虽然人们普遍认为肌肽的有益作用是由于其抗氧化剂，抗糖基化终产物（AGE）和先进的脂氧化终产物（ALE）和抗炎特性，但尚不能解释这种作用的分子机制。被明确定义。研究表明肌肽通过直接的抗氧化剂机制和螯合脂质和葡萄糖氧化的副产物活性羰基（RCS）起作用，从而抑制AGE和ALE，这是RCS与蛋白质的反应产物。此外，还发现肌肽可通过激活Nrf2转录因子间接发挥作用，该机理可解释该肽引起的许多作用，例如抗炎，抗氧化，抗糖基化和抗羰基作用，加在一起可解释其治疗作用。本综述报告并讨论了有关肌肽分子机制的最新研究，在推广肌肽及其衍生物作为治疗剂之前需要充分阐明。