RESUMO
The pathogenesis of diabetes is related to the amount of advanced glycation end products (AGEs) that are naturally generated from the attachment of glucose with tissue and circular proteins. Human serum albumin (HSA) is more susceptible to AGE occurrence than other circular proteins due to its sensitive sites and high abundance. Considering the location of hydroxyl groups in the structure of flavonoids, which play a major role in suppressing of AGEs generating pathways, the present study was conducted to compare the effect of the chemical peculiarities of five flavonoids: apigenin (AP), naringenin (NA), luteolin (LU), Quercetin (QU), and methylquercetin (MQ), in suppressing AGEs generated in the HSA/glucose system. The results showed that all used flavonoids are capable of quenching the fluorescence intensity of AGEs in vitro. Analytical methods including UV-visible spectroscopy, CD spectro-polarimetry, TNBS, DTNB, DNPH, Congo red assay, ThT, and ANS fluorescence were used to deeper analysis of flavonoid performance. The anti-AGE effects of flavonoids followed the order of LU > QU > MQ > AP > NA. Docking results showed that flavonoids are associated with glycation-prone lysines and arginine residues in the "Sudlow pocket" through non-covalent interactions. Hydroxylation at the C4' and the double bond between C2-C3 increase the antiglycation potential of used flavonoids, while methylation of the OH group at the C3 position decreases this effect. It was also found that hydroxylation at C3 can play a dual role in anti-glycation ability. These findings may introduce a new approach to the structure-inhibition relationship of flavonoids in the design of operative anti-glycemic agents.
RESUMO
BACKGROUND: Bisphosphonates (BPs) are used extensively for managing the osteoporosis. There are some controversies on atypical fractures of femur that associated with increase in cortical thickness (CT) and BPs' use. In this study, the effects of alendronate consumption were studied on femoral CT as a predictor for atypical fracture. METHODS: Forty nine post-menopausal women aged 50-70 years with osteopenia-osteoporosis who were treated with alendronate 70 mg/week for at least one year were compared to 49 controls for CT in subtrochanteric region of femur by hip dual-energy X-ray absorptiometry (DXA) scans and hip Xray. CT and its ratio were measured at 3.5 and 4.0 cm below the tip of the greater trochanter (GT) and 0.5 cm below lesser trochanter (LT) in DXA and at 9.5 and 10.5 cm of GT and 1 cm of LT in Xray. RESULTS: In this study, 98 women participated whose mean age and age at menopause were 60 (17±5.6) and 49 (40±2.7) years, respectively. Duration of BP consumption in alendronate group was 1.76±1.38 (1-10) years. No difference was seen in the mean of CT and its ratio between the alendronate and control groups in BMD scan or X-ray. The best correlation between two imaging modalities was in cortical ratio in 3.5 cm of GT in BMD scan and 9.5 cm of GT in X-ray. CONCLUSION: Alendronate treatment did not appear to increase femoral CT throughout the detection limits of BMD scan or X-ray.
