Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Eur Rev Med Pharmacol Sci. 2018 May;22(10):3261-3273. doi: 10.26355/eurrev_201805_15089.
The water-soluble vitamin, thiamine forms an important part of the diet because of its role in the energy metabolism. The protective effects of thiamine against diabetic vascular complications have been well documented. However, slower absorption and reduced bioavailability is a major limiting factor for its clinical use. To overcome this issue, lipid-soluble derivatives of thiamine (allithiamines) was developed. Among the many synthetic lipophilic derivatives of thiamine, benfotiamine (BFT) is regarded as the first choice based on its safety and clinical efficacy data. BFT facilitates the action of thiamine diphosphate, a cofactor for the enzyme transketolase. The activation of transketolase enzyme accelerates the precursors of advanced glycation end products (AGEs) towards the pentose phosphate pathway thereby reducing the production of AGEs. The reduction in AGEs subsequently decreases metabolic stress which benefits vascular complications seen in diabetes. The effects of BFT on the AGE-dependent pathway is well established. However, several studies have shown that BFT also modulates pathways other than AGE such as arachidonic acid (AA), nuclear transcription Factor κB (NF-κβ), protein kinase B, mitogen-activated protein kinases (MAPK) and vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathways. In the present review, we have comprehensively reviewed all the molecular targets modulated by BFT to provide mechanistic perspective to highlight its pleiotropic effects.
水溶性维生素硫胺素因其在能量代谢中的作用而成为饮食的重要组成部分。硫胺素对糖尿病血管并发症的保护作用已有充分的文献记载。然而，其吸收缓慢和生物利用度降低是其临床应用的主要限制因素。为了克服这个问题，开发了硫胺素的脂溶性衍生物（硫胺素类似物）。在许多硫胺素的合成亲脂性衍生物中，基于其安全性和临床疗效数据，苯磷硫胺（BFT）被认为是首选。BFT 促进了硫胺素二磷酸的作用，硫胺素二磷酸是转酮醇酶的辅助因子。转酮醇酶的激活加速了晚期糖基化终产物（AGEs）的前体向戊糖磷酸途径的转化，从而减少了 AGEs 的产生。AGEs 的减少随后降低了代谢应激，从而有益于糖尿病中出现的血管并发症。BFT 对 AGE 依赖性途径的影响已得到充分证实。然而，几项研究表明，BFT 还调节 AGE 以外的途径，如花生四烯酸（AA）、核转录因子 κB（NF-κβ）、蛋白激酶 B、丝裂原活化蛋白激酶（MAPK）和血管内皮生长因子受体 2（VEGFR2）信号通路。在本综述中，我们全面回顾了 BFT 调节的所有分子靶点，以提供机制视角来突出其多效性作用。
