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Therapeutic potential of benfotiamine and its molecular targets.
Eur Rev Med Pharmacol Sci 2018; 22(10):3261-3273ER

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-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.

Authors+Show Affiliations

Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. sandeep.bs@uaeu.ac.ae.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

29863274

Citation

Raj, V, et al. "Therapeutic Potential of Benfotiamine and Its Molecular Targets." European Review for Medical and Pharmacological Sciences, vol. 22, no. 10, 2018, pp. 3261-3273.
Raj V, Ojha S, Howarth FC, et al. Therapeutic potential of benfotiamine and its molecular targets. Eur Rev Med Pharmacol Sci. 2018;22(10):3261-3273.
Raj, V., Ojha, S., Howarth, F. C., Belur, P. D., & Subramanya, S. B. (2018). Therapeutic potential of benfotiamine and its molecular targets. European Review for Medical and Pharmacological Sciences, 22(10), pp. 3261-3273. doi:10.26355/eurrev_201805_15089.
Raj V, et al. Therapeutic Potential of Benfotiamine and Its Molecular Targets. Eur Rev Med Pharmacol Sci. 2018;22(10):3261-3273. PubMed PMID: 29863274.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic potential of benfotiamine and its molecular targets. AU - Raj,V, AU - Ojha,S, AU - Howarth,F C, AU - Belur,P D, AU - Subramanya,S B, PY - 2018/6/5/entrez PY - 2018/6/5/pubmed PY - 2019/10/31/medline SP - 3261 EP - 3273 JF - European review for medical and pharmacological sciences JO - Eur Rev Med Pharmacol Sci VL - 22 IS - 10 N2 - 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-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. SN - 2284-0729 UR - https://www.unboundmedicine.com/medline/citation/29863274/Therapeutic_potential_of_benfotiamine_and_its_molecular_targets_ L2 - https://www.europeanreview.org/article/15089 DB - PRIME DP - Unbound Medicine ER -