AI Article Synopsis
- Inhibition of advanced glycation end-product (AGE) formation could help prevent complications from diabetes, with research discovering natural compounds that effectively block the formation of CML, a key AGE.
- Some natural compounds, especially those with catechol groups like gallic acid and epicatechin, actually increase CML formation, especially when tested on macrophages and diabetes models.
- The study highlights that the increased CML formation from catechol compounds is related to oxidative stress and hydrogen peroxide, suggesting that while some flavonoids might seem beneficial, they can actually worsen redox status in certain conditions.
Article Abstract
Inhibition of advanced glycation end-product (AGE) formation is a potential strategy for the prevention of clinical diabetes complications. Screening for new AGE inhibitors revealed several natural compounds that inhibited the formation of N(ε)-(carboxymethyl)lysine (CML), a major antigenic AGE structure, whereas natural compounds containing a catechol group, such as gallic acid and epicatechin, significantly enhanced CML formation. A similar enhancing effect was also observed by culturing THP-1 macrophages in the presence of catechol compounds. Although 4-methylcatechol significantly enhanced CML formation from glycated HSA (gHSA), a model for Amadori proteins, analogues of catechol such as 5-methylresorcinol and methylhydroquinone showed no enhancing effect. Even though 1mM 4-methylcatechol, epicatechin, and gallic acid significantly enhanced CML formation from gHSA, it was significantly inhibited by decreasing their concentration. The enhancing effect of 1mM catechol compounds was inhibited in the presence of the glutathione peroxidase system, thus demonstrating that hydrogen peroxide generated from catechol compounds plays an important role in the enhancement of CML formation. Furthermore, administration of 500mg/kg/day epicatechin to STZ-induced diabetic mice for 45days enhanced CML accumulation at the surface area of gastric epithelial cells in the stomach. This study provides the first evidence that high amounts of catechol-containing structures enhance oxidative stress, thus leading to enhanced CML formation, and this phenomenon may explain the paradoxical effect that some flavonoids have on redox status.
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| http://dx.doi.org/10.1016/j.freeradbiomed.2010.12.033 | DOI Listing |
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