Combined effect of total flavonoids from seed residues of Hippophae rhamnoides L. and zinc on advanced glycation end products-induced endothelial cell dysfunction

Accumulation of advanced glycation end products (AGEs) and impaired zinc levels are observed in diabetes. Previous studies have demonstrated that total flavonoids from seed residues of Hippophae rhamnoides L. (FSH) is effective in controlling serum glucose in diabetic rats. The present study investigated the use of FSH or FSH combined with ZnCl₂ (FSH–ZnCl₂) on AGEs-mediated endothelial cell dysfunction. Cellular zinc levels, nitric oxide (NO) production, endothelial NO synthase (eNOS) expression and activity, and superoxide dismutase (SOD) activity were significantly depressed, while reactive oxygen species levels and nuclear transcription factor kappa B activation were increased by AGEs. FSH supplementation counteracted these changes, and FSH–ZnCl₂ treatment was more effective in upregulating NO generation, eNOS expression, and total SOD activity than the use of FSH. In conclusion, FSH or FSH–ZnCl₂ treatment reversed many changes observed in AGEs-induced endothelial cell dysfunction, and should therefore be considered in further studies of therapy for diabetic complications.