RESUMO
Natural polyphenols are major constituents of plant foods and herbs. Numerous reports demonstrated that these compounds inhibited amyloid formation and destabilized the preformed amyloid fibrils. The present study, utilizing bovine insulin as a model peptide, examined the antiamyloidogenic effects of fisetin (3,7,3',4'-tetrahydroxyflavone). Fluorescent probes, transmission electron microscopy and hemolytic assay were utilized to determine the roles of fisetin on amyloidogenesis of insulin. The results demonstrated that fisetin dose-dependently inhibited amyloid formation of insulin. Moreover, fisetin disaggregated the preformed insulin fibrils and transformed the fibrils into non-amyloid structures. Hemolysis was observed when erythrocytes were co-incubated with insulin fibrils. Fisetin inhibited fibril-induced hemolysis in a dose-dependent manner. Hydrophobic interaction is suggested to be a key driving force in the anti-amyloidogenic and fibril-disaggregating effects of fisetin. The results of the present work suggest that fisetin is an effective anti-amyloidogenic compound and may serve as a lead structure for the design of novel drugs for the treatment of amyloid diseases.
RESUMO
Melanocyte loss in vitiligo vulgaris is believed to be an autoimmune process. Macrophage migration inhibitory factor (MIF) is involved in many autoimmune skin diseases. We determined the possible role of MIF in the pathogenesis of vitiligo vulgaris, and describe the relationship between MIF expressions and disease severity and activity. Serum MIF concentrations and mRNA levels in PBMCs were measured in 44 vitiligo vulgaris patients and 32 normal controls, using ELISA and real-time RT-PCR. Skin biopsies from 15 patients and 6 controls were analyzed by real-time RT-PCR. Values are reported as median (25th-75th percentile). Serum MIF concentrations were significantly increased in patients [35.81 (10.98-43.66) ng/mL] compared to controls [7.69 (6.01-9.03) ng/mL]. MIF mRNA levels were significantly higher in PBMCs from patients [7.17 (3.59-8.87)] than controls [1.67 (1.23-2.42)]. There was also a significant difference in MIF mRNA levels in PBMCs between progressive and stable patients [7.86 (5.85-9.13) vs 4.33 (2.23-8.39)] and in serum MIF concentrations [40.47 (27.71-46.79) vs 26.80 (10.55-36.07) ng/mL]. In addition, the vitiligo area severity index scores of patients correlated positively with changes of both serum MIF concentrations (r = 0.488) and MIF mRNA levels in PBMCs (r = 0.426). MIF mRNA levels were significantly higher in lesional than in normal skin [2.43 (2.13-7.59) vs 1.18 (0.94-1.83)] and in patients in the progressive stage than in the stable stage [7.52 (2.43-8.84) vs 2.13 (1.98-2.64)]. These correlations suggest that MIF participates in the pathogenesis of vitiligo vulgaris and may be useful as an index of disease severity and activity.