Potencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivo

Abstract

Iron (Fe) and glucose (GLU) are essential elements for most forms of life. However, the progressive increase inevitably leads to pathological conditions, such as Fe overload and diabetes disease. Drug therapy consists in the use of binders and antidiabetics, however, the drugs available have numerous restrictions on use and adverse effects, making the therapy unsatisfactory. Due to the existing difficulties, the need for further research is essential. Recent studies demonstrate that Phenolic Compounds are important in this search. Among Them, there are caffeic acid (CA) and ferulic acid (FA), known for their antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, antitumor, hepatoprotective, nephroprotective and neuroprotective activity already described. Therefore, the objective was to evaluate behavior of the compounds in silico and in vivo. For this, the in silico toxic risk assessment was performed using the pkCSM, lazar, OSIRIS, ProTox-II and admetSAR tools, and pharmacophoric models of CA and FA wereals developed against the proteins of GLU and Fe metabolism via molecular docking. The results obtained the in silico prediction did not show significant toxicological effects. Subsequently, two in vivo studies with Wistar rats were developed. In the first study, the induced groups received Fe dextran and treated groups CA, FA and CA+FA (10 mg/kg/day), while the control group received desferrioxamine (DFO). Biochemical and hematological parameters and tissue oxidative stress markers were analyzed. The experimental model showed increased levels serum Fe and changes in several parameters such as GLU, liver markers and heart damage. CA demonstrated better control of the effects from Fe overload and the association acid did not demonstrate synergism. Docking showed that carbonic anhydrase interacted with the test molecules and CA showed less energy expenditure in this interaction. In the second study, to induce diabetes, the animals received streptozotocin (STZ) (55 mg/kg), treated groups received CA and FA and CA+FA at a dose of 10 mg/kg/day, and control group received an equivalent volume of filtered water or metformin (100 mg/kg). Treated animals showed improvement in blood glucose and biochemical markers when compared to untreated animals. Dockings howed that α-glucosidase inhibition possibly the cause of improvement in diabetic disease. In these results, there are indications that CA and FA may have therapeutic potential in the treatment diseases, like diabetic disease and Fe overload.