ABSTRACT
Bergapten, a furocoumarin found in many medicinal plants, is used for the management of various conditions. The present in vitro study evaluated the ability of bergapten to prevent human erythrocyte hemolysis and protein denaturation. Bergapten administered at 10, 30, and 100 µg/ml exhibited a significant concentration-dependent protection on the erythrocyte membrane exposed to hypotonicity and heat-induced hemolysis. The concentration at which bergapten inhibited 50% of the cells from hemolysis (IC50) was determined on a dose-response curve, plotted as logarithmic (concentration) against percentage inhibition, keeping the hemolysis produced within the control group at 100%. Bergapten treatment produced an IC50 value of 7.71 ± 0.27 µg/ml and 4.23 ± 0.42 µg/ml for hypotonicity and heat-induced hemolysis, respectively. Diclofenac sodium at similar concentrations produced an IC50 value of 12.22 ± 0.30 µg/ml and 9.44 ± 0.23 µg/ml in the hypotonicity and heat-induced hemolysis, respectively. The ability of bergapten to inhibit protein denaturation was studied as part of an investigation on its mechanism of action. The results showed a significant concentration-dependent reduction in protein denaturation. When administered at 10, 30, and 100 µg/ml, bergapten produced a concentration-dependent reduction in albumin denaturation. Bergapten inhibited protein denaturation with IC50 values of 5.34 ± 0.30 µg/ml and 12.18 ± 0.20 µg/ml in the heat-treated egg albumin and bovine serum albumin denaturation experiments, respectively. Diclofenac sodium (10, 30, and 100 µg/ml) exhibited a similar protection against heat-treated egg albumin and bovine serum albumin denaturation experiments with IC50 values of 8.93 ± 0.17 µg/ml and 12.72 ± 0.11 µg/ml, respectively. Taken together, data from this study show that the pharmacological properties of bergapten may in part be related to its membrane-stabilizing and antidenaturation properties.
ABSTRACT
ABSTRACT: SIRT1, a member of the sirtuin family of longevity regulators, possesses potent activities preventing vascular aging. The expression and function of SIRT1 in endothelial cells are downregulated with age, in turn causing early vascular aging and predisposing various vascular abnormalities. Overexpression of SIRT1 in the vascular endothelium prevents aging-associated endothelial dysfunction and senescence, thus the development of hypertension and atherosclerosis. Numerous efforts have been directed to increase SIRT1 signaling as a potential strategy for different aging-associated diseases. However, the complex mechanisms underlying the regulation of SIRT1 have posed a significant challenge toward the design of specific and effective therapeutics. This review aimed to provide a summary on the regulation and function of SIRT1 in the vascular endothelium and to discuss the different approaches targeting this molecule for the prevention and treatment of age-related cardiovascular and cerebrovascular diseases.