Department of Pharmacology, SB College of Pharmacy, Sivakasi 626130, India.
Pharmacol Res. 2010 Jun;61(6):482-8. doi: 10.1016/j.phrs.2010.02.008. Epub 2010 Feb 25.
Thiamine, known as vitamin B(1), plays an essential role in energy metabolism. Benfotiamine (S-benzoylthiamine O-monophoshate) is a synthetic S-acyl derivative of thiamine. Once absorbed, benfotiamine is dephosphorylated by ecto-alkaline phosphatase to lipid-soluble S-benzoylthiamine. Transketolase is an enzyme that directs the precursors of advanced glycation end products (AGEs) to pentose phosphate pathway. Benfotiamine administration increases the levels of intracellular thiamine diphosphate, a cofactor necessary for the activation transketolase, resulting in the reduction of tissue level of AGEs. The elevated level of AGEs has been implicated in the induction and progression of diabetes-associated complications. Chronic hyperglycemia accelerates the reaction between glucose and proteins leading to the formation of AGEs, which form irreversible cross-links with many macromolecules such as collagen. In diabetes, AGEs accumulate in tissues at an accelerated rate. Experimental studies have elucidated that binding of AGEs to their specific receptors (RAGE) activates mainly monocytes and endothelial cells and consequently induces various inflammatory events. Moreover, AGEs exaggerate the status of oxidative stress in diabetes that may additionally contribute to functional changes in vascular tone control observed in diabetes. The anti-AGE property of benfotiamine certainly makes it effective for the treatment of diabetic neuropathy, nephropathy and retinopathy. Interestingly, few recent studies demonstrated additional non-AGE-dependent pharmacological actions of benfotiamine. The present review critically analyzed the multifaceted therapeutic potential of benfotiamine.
硫胺素，又称维生素 B(1)，在能量代谢中起着至关重要的作用。苯磷硫胺（S-苯甲酰硫胺素 O-单磷酸酯）是硫胺素的一种合成 S-酰基衍生物。一旦被吸收，苯磷硫胺就会被碱性磷酸酶外切脱磷酸化为脂溶性的 S-苯甲酰硫胺。转酮醇酶是一种酶，它将晚期糖基化终产物（AGEs）的前体导向戊糖磷酸途径。苯磷硫胺的给药会增加细胞内硫胺素二磷酸的水平，这是激活转酮醇酶所必需的辅因子，从而导致组织中 AGEs 的水平降低。AGEs 水平的升高与糖尿病相关并发症的诱导和进展有关。慢性高血糖加速了葡萄糖与蛋白质之间的反应，导致 AGEs 的形成，AGEs 与许多大分子如胶原蛋白形成不可逆的交联。在糖尿病中，AGEs 以加速的速度在组织中积累。实验研究表明，AGEs 与其特异性受体（RAGE）结合主要激活单核细胞和内皮细胞，从而诱导各种炎症事件。此外，AGEs 加剧了糖尿病中氧化应激的状态，这可能进一步导致糖尿病中观察到的血管张力控制的功能变化。苯磷硫胺的抗 AGE 特性使其对治疗糖尿病性神经病、肾病和视网膜病变非常有效。有趣的是，最近的一些研究表明了苯磷硫胺的其他非 AGE 依赖性药理学作用。本综述批判性地分析了苯磷硫胺的多方面治疗潜力。
