Therapeutic potential of benfotiamine and its molecular targets

V. Raj, S. Ojha, F. C. Howarth, P. D. Belur, S. B. Subramanya

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

OBJECTIVE: 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-κß), 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.

Original languageEnglish
Pages (from-to)3261-3273
Number of pages13
JournalEuropean review for medical and pharmacological sciences
Volume22
Issue number10
Publication statusPublished - 2018

Keywords

  • Allithiamine
  • Benfotiamine
  • Thiamin and advanced glycation end products

ASJC Scopus subject areas

  • Pharmacology (medical)

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