Antidiabetic Potential of Mangiferin: An In Silico and In Vivo Approach

<b>Objectives:</b> According to published data, mangiferin has the potential to prevent diabetes mellitus. The aim of this work was to obtain in vivo evidence of the biological activity of mangiferin predicted in silico. <b>Methods:</b> A prediction using the IT Microcosm system was employed to identify the correlation between the spatial structure of mangiferin and its biological activity. <i>MAPK10</i>, <i>HCAR2</i>, and <i>CALCRL</i> biotargets were used as the basis for predicting moderate antiglycation activity in silico. The presence of anti-inflammatory and antidiabetic activities in mangiferin was empirically tested in in vivo models. To assess anti-inflammatory activity in female Sprague-Dawley rats, acute exudative inflammation and chronic proliferative inflammation were induced. To assess hypoglycemic activity in female Sprague-Dawley rats, diabetes mellitus was modeled with an alloxan solution (150.0 mg/kg). During the experiment, fasting body weight, glucose, and total cholesterol concentrations in the blood serum of the animals were assessed weekly. To study hypocholesterolemic activity in female <i>Mus musculus</i> mice, hypercholesterolemia was modeled by administering a solution of Kolliphor P 407 three times a week. Mangiferin (50.0 mg/kg, 100.0 mg/kg) was administered orally daily for 7 days (in the last week of the experiment) or for 14 days (hypercholesterolemia model). <b>Results:</b> In vivo studies showed that mangiferin showed pro-inflammatory activity without affecting body weight and did not reduce glucose and cholesterol concentrations. The obtained results contribute to the evidence regarding the presence/absence of the anti-inflammatory, hypoglycemic, and hypocholesterolemic properties of mangiferin. <b>Conclusions:</b> The discrepancy between mangiferin's actual activity and the in silico predictions suggests the need for further studies using lower doses of mangiferin and investigating approaches to enhance its bioavailability.