Disease relevance of S-Benzoylthiamine monophosphate

• Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy [1].
• The ability of benfotiamine to inhibit three major pathways simultaneously might be clinically useful in preventing the development and progression of diabetic complications [1].
• Our results indicate that hyperglycemia impairs EPC differentiation and that the process can be restored by benfotiamine administration, via the modulation of Akt/FoxO1 activity [2].
• High-dose thiamine and benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy [3].
• Benfotiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/FoxO signaling [2].

High impact information on S-Benzoylthiamine monophosphate

• In retinas of diabetic animals, benfotiamine treatment inhibited these three pathways and NF-kappaB activation by activating transketolase, and also prevented experimental diabetic retinopathy [1].
• Thiamine and benfotiamine reduce aldose reductase mRNA expression, activity, sorbitol concentrations, and intracellular glucose while increasing the expression and activity of transketolase, for which it is a coenzyme, in human endothelial cells and bovine retinal pericytes cultured in high glucose [4].
• To determine the effect of glucotoxicity on EPCs, human EPCs have been isolated from peripheral blood mononuclear cells of healthy donors and cultured in the presence or absence of high glucose (33 mmol/l) or high glucose plus benfotiamine to scavenge glucotoxicity [2].
• High-dose thiamine and benfotiamine therapy increased transketolase expression in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate, and strongly inhibited the development of microalbuminuria [3].
• The functional importance of PKB/Akt in benfotiamine-induced effects was investigated using a dominant-negative construct [5].

Chemical compound and disease context of S-Benzoylthiamine monophosphate

• In the ESRD patients, after 24 h, the mean TDP concentration in erythrocytes increased from 158.7+/-30.9 ng/ml initially to 325.8+/-50.9 ng/ml after administration of benfotiamine and from 166.2+/-51.9 ng/ml to 200.5+/-50.0 ng/ml after thiamine nitrate administration [6].
• OBJECTIVE: The aim of the study was to evaluate the efficacy of benfotiamine administered over three weeks (allithiamine; a lipid-soluble vitamin B1 prodrug with high bioavailability) to patients with diabetic polyneuropathy in a randomized, placebo-controlled, double-blind, two-center pilot study [7].
• To understand the chemical basis of thi-box pyrophosphate specificity, we have determined crystal structures of an E. coli thi-box bound to thiamine pyrophosphate, thiamine monophosphate, and the structural analogs benfotiamine and pyrithiamine [8].

Biological context of S-Benzoylthiamine monophosphate

• CONCLUSIONS/INTERPRETATION: We have demonstrated, for the first time, that benfotiamine aids the post-ischaemic healing of diabetic animals via PKB/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis [5].
• Importantly, benfotiamine prevented ischaemia-induced toe necrosis, improved hindlimb perfusion and oxygenation, and restored endothelium-dependent vasodilation [5].
• Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes [9].
• Bioavailability assessment of the lipophilic benfotiamine as compared to a water-soluble thiamin derivative [10].
• Pharmacokinetics of thiamine derivatives especially of benfotiamine [11].

Anatomical context of S-Benzoylthiamine monophosphate

• The aim of this study was to evaluate whether benfotiamine is of benefit in reparative neovascularisation using a type I diabetes model of hindlimb ischaemia [5].

Associations of S-Benzoylthiamine monophosphate with other chemical compounds

• The transketolase activity increased from 3.54+/-0.7 microkat/l initially to 3.84+/-0.6 microkat/l after benfotiamine intake (P = 0.02) and from 3.71+/-0.8 microkat/l to 4.02+/-0.7 microkat/l after thiamine nitrate intake (P = 0.08) [6].
• It is quite clear that benfotiamine is absorbed much more better than water-soluble thiamine salts: maximum plasma levels of thiamine are about 5 times higher after benfotiamine, the bioavailability is at maximum about 3.6 times as high as that of thiamine hydrochloride and better than other lipophilic thiamine derivates [11].

Gene context of S-Benzoylthiamine monophosphate

• In addition, benfotiamine prevented the vascular accumulation of advanced glycation end products and the induction of pro-apoptotic caspase-3, while restoring proper expression of Nos3 and Akt in ischaemic muscles [5].
• We also investigated the involvement of protein kinase B (PKB)/Akt in the therapeutic effects of benfotiamine [5].
• RESULTS: Diabetic muscles showed reduced transketolase activity, which was corrected by benfotiamine [5].
• The effects of HAGE on both FMD and reactive hyperemia were completely prevented by benfotiamine [9].
• Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha [12].

Analytical, diagnostic and therapeutic context of S-Benzoylthiamine monophosphate

• Results indicate that oral administration of benfotiamine is able to reduce tactile allodynia from different origin in the rat and they suggest the use of this drug to reduce inflammatory and neuropathic pain in humans [13].
• CONCLUSION: This pilot investigation (BEDIP Study) has confirmed the results of two earlier randomized controlled trials and has provided further evidence for the beneficial effects of benfotiamine in patients with diabetic neuropathy [7].
• SUBJECTS, MATERIAL AND METHODS: After a single oral dose of either 100 mg benfotiamin (S-benzoylthiamine-o-monophosphate, BTMP) or 100 mg thiamine mononitrate (TN), blood levels of thiamine phosphate esters were analyzed by HPLC after precolumn derivatization to thiochrome phosphate esters for a 24-hour period [14].
• A three-armed, randomized, multicentre, placebo-controlled double-blind study was used to examine the efficacy of benfotiamine vs a combination containing benfotiamine and vitamins B6 and B12 in out-patients with severe symptoms of alcoholic polyneuropathy (Benfotiamine in treatment of Alcoholic Polyneuropathy, BAP I) [15].

References