Antiglycation, antifibrillation and antioxidative effects of para coumaric acid and vitamin D; an in-vitro and in-silico comparative-cum-synergistic approach

Abstract

Diabetes Mellitus is a metabolic disorder that results in impaired utilization of carbohydrates, lipids, and proteins. Severe hyperglycemia is its principal clinical symptom. Human serum albumin (HSA) is used as a model protein since it is viewed as a sign of glycaemic management because it is more likely to get glycated in diabetic people than other proteins. Para-coumaric acid (pCA), a phenolic acid, and Vitamin D (vit-D) are used as protective agents. In the present work, we deduce a synergistic-cum-comparative effect of pCA and vit-D, expecting some improvement in the efficacy of pCA when combined with vit-D. Methods employed are DPPH radical scavenging activity, In-vitro glycation of HSA, UV–vis spectroscopy, fluorescence analysis, and circular dichroism measurement. After treatment, increasein the absorbance and fluorescence intensity were reduced along with normalization of CD value. . The glycation-mediated fibrillation assessed by Congo-Red and Thioflavin T (ThT) were found to be diminishedwhen HSA was treated with equimolar concentration of p-CA and vit-D- treatment. Fructosamine adduct formation and lysine modificationwas also decreased, while inhibition to hemolysis and lipid peroxidation was found to increase upon treatment. The reactive oxygen species generation detection was also performed in lymphocytes treated with various protein samples. Docking results further confirmed theblocking some glycation-prone amino acids by both compounds. The study shows that the combination in the ratio of 1:1 has provided higher overall protection comparable to aminoguanidine (AG), the molecule which is utilized as a positive control.