Evaluation of the Chemical Composition, Antioxidant and Antidiabetic Activity of Rhaponticoides iconiensis Flowers: Effects on Key Enzymes Linked to Type 2 Diabetes In Vitro, In Silico and on Alloxan-Induced Diabetic Rats In Vivo

Diabetes mellitus (DM) is one of the globally worst killer diseases. In this study, the in vitro and in vivo antidiabetic activity and antioxidant capacity were determined and the phytochemical analyses were carried out on flower extract and sub-extracts of Rhaponticoides iconiensis. The in vitro antidiabetic activity was tested with alpha-amylase and alpha-glucosidase enzyme inhibition methods and an in vivo OGTT test in healthy and alloxan-induced rats. Although, the antioxidant activity was investigated with DPPH?, ABTS(?+) and FRAP tests, the phytochemical composition analysis was carried out by LC-MS/MS. The highest alpha-glucosidase and alpha-amylase activity even from positive control acarbose were found in the ethyl acetate sub-extract of R. iconiensis (IC50 = 11.737 +/- 0.823 mu g/mL and 84.247 +/- 0.721 mu g/mL, respectively). This sub-extract also was active according to the results of in vivo tests. Moreover, the highest antioxidant activity on DPPH? (IC50 = 0.126 +/- 0.002 mg/mL), FRAP (at a concentration of 1 mg/mL equivalent to 3112.052 +/- 2.023 mmol Fe2+) and ABTS(+?) (at a concentration of 0.5 mg/mL equivalent to 0.608 +/- 0.005 mu M Trolox) tests. In addition, LC-MS/MS analyses of the active sub-extract revealed mainly the presence of patuletin, patuletin 3,7-diglucoside, naringin and 3,4-dicaffeoylquinic acid detected in the active sub-extract. In silico molecular docking and dynamics simulations studies were performed on these compounds with alpha-amylase and alpha-glucosidase enzymes for protein-ligand interactions and stability.

Automated summary

In this study, the antidiabetic and antioxidant activities of flower extract and sub-extracts of Rhaponticoides iconiensis were investigated. The ethyl acetate sub-extract showed the highest activity against alpha-glucosidase and alpha-amylase enzymes, as well as the highest antioxidant activity. The LC-MS/MS analysis revealed the presence of several active compounds. Molecular docking and dynamics simulations studies were performed to understand the protein-ligand interactions and stability.