Babizhayev Mark A, Yegorov Yegor E
Innovative Vision Products, Inc., Moscow Division, Ivanovskaya 20, Suite 74 Moscow 127434 Russian Federation.
Recent Pat Drug Deliv Formul. 2015;9(1):1-64. doi: 10.2174/1872211309666141218145408.
Hypothalamic releasing and inhibiting hormones are major neuroendocrine regulators of human body metabolism being driven directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. The alternative physiological or therapeutic interventions utilizing the pharmaco-nutritional boost of imidazole-containing dipeptides (non-hydrolized oral form of carnosine, carcinine, N-acetylcarnosine lubricant eye drops) can maintain health, enhance physical exercise performance and prevent ageing. Carnosine (β-alanyl-L-histidine) is synthesized in mammalian skeletal muscle. There is an evidence that the release of carnosine from the skeletal muscle sarcomeres moieties during physical exercise affects autonomic neurotransmission and physiological functions. Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function. Carnosine and its imidazole-containing dipeptide derivatives are renowned for their anti-aging, antioxidant, membrane protective, metal ion chelating, buffering, anti-glycation/ transglycating activities used to prevent and treat a spectrum of age-related and metabolic diseases, such as neurodegenerative disease, sight threatening eye diseases, Diabetes mellitus and its complications, cancers and other disorders due to their wide spectrum biological activities. The precursor of carnosine (and related imidazole containing compounds) synthesis in skeletal muscles beta-alanine is used as the oral supplement by athletes to achieve the fine sporting art results due to the buffering activities of carnosine and its related imidazole- containing compounds which contribute to the maintenance of the acid-base balance in the acting muscles. This work originally emphasizes that overall data indicate the signaling activities of carnosine in skeletal and cardiac muscles switching on the mechanisms of exercise-induced telomere protection and point to the stress response and growth/cellular proliferation pathways as high-priority candidates for the ongoing studies and therapeutic concepts. The therapeutic interventions utilizing the specific oral formulation (Can-C Plus), timing dosing and pharmaco-nutritional boost of imidazolecontaining dipeptides can maintain health, enhance physical exercise performance and prevent aging. The patented therapeutic concept protects the existence of the interesting physiological major activities, better controls and therapeutic treatments for aging/age-related disorders (including age-related loss of muscle mass and muscle function) using carnosine dipeptide for cellular rejuvenation and manipulating telomeres and enzyme telomerase activity that may reduce some of the physiological declines that accompany aging.
下丘脑释放和抑制激素是人体新陈代谢的主要神经内分泌调节因子,通过下丘脑 - 垂体门脉直接作用于腺垂体。利用含咪唑二肽的药物营养增强作用(肌肽、鹅肌肽的非水解口服形式、N - 乙酰肌肽润滑眼药水)的替代生理或治疗干预措施可以维持健康、提高体育锻炼表现并预防衰老。肌肽(β - 丙氨酰 - L - 组氨酸)在哺乳动物骨骼肌中合成。有证据表明,体育锻炼期间肌肽从骨骼肌肌节部分释放会影响自主神经传递和生理功能。运动期间从骨骼肌释放的肌肽作为一种强大的传入生理信号刺激下丘脑,可能被转运到下丘脑结节乳头核(TMN),特别是转运到TMN - 组胺能神经元,并通过原位存在的肌肽降解酶(肌肽酶2)的活性在此处水解。通过组胺能神经元中组氨酸脱羧酶的共定位酶活性,产生的L - 组氨酸随后可能转化为组胺,这可能是肌肽对神经传递和生理功能产生影响的原因。肌肽及其含咪唑二肽衍生物因其抗衰老、抗氧化、膜保护、金属离子螯合、缓冲、抗糖基化/转糖基化活性而闻名,这些活性可用于预防和治疗一系列与年龄相关的代谢疾病,如神经退行性疾病、威胁视力的眼部疾病、糖尿病及其并发症、癌症和其他疾病,因为它们具有广泛的生物活性。骨骼肌中肌肽(及相关含咪唑化合物)合成的前体β - 丙氨酸被运动员用作口服补充剂,以获得良好的运动成绩,这是由于肌肽及其相关含咪唑化合物的缓冲活性有助于维持运动肌肉中的酸碱平衡。这项工作最初强调,总体数据表明肌肽在骨骼肌和心肌中的信号传导活动开启了运动诱导的端粒保护机制,并指出应激反应和生长/细胞增殖途径是正在进行的研究和治疗概念的高优先级候选对象。利用特定口服制剂(Can - C Plus)、定时给药和含咪唑二肽的药物营养增强作用的治疗干预措施可以维持健康、提高体育锻炼表现并预防衰老。该专利治疗概念保护了有趣的生理主要活动的存在,使用肌肽二肽进行细胞 rejuvenation 以及操纵端粒和端粒酶活性,从而更好地控制和治疗衰老/与年龄相关的疾病(包括与年龄相关的肌肉质量和肌肉功能丧失),这可能会减少一些伴随衰老的生理衰退。