Exploration of the Antidiabetic Potential of Typical Compounds from Butterfly Pea Flowers (Clitoria ternatea (L.)) against PPAR-γ Receptors through Molecular Docking

Abstract

Type 2 diabetes mellitus is a type of diabetes associated with resistance and impaired insulin secretion due to abnormal pancreatic beta cell function. Butterfly pea flowers (Clitoria ternatea (L.) contain phenolic compounds, flavonoids, and anthocyanins that have the potential to act as antidiabetics. One of the receptors targeted for diabetes treatment is PPAR-γ. The purpose of this study was to determine the type of butterfly pea flower anthocyanin that has the best activity compared to the pioglitazone ligand, the interactions formed, and analyze its pharmacokinetic and toxicity profiles. The method used was molecular docking with Autodock Vina, with 3 experiments carried out to ensure the accuracy of the results. The docking results showed that anthocyanin compounds have lower binding energy than pioglitazone. The best compound is Ternatin A2 (-10.46 ± 0.66 kcal/mol). In addition, flavonoid compounds such as Quercetin 3-O-rutinoside (-10.56 ± 0.00 kcal/mol) and Kaempferol 3-neohesperidoside (-9.70 ± 0.00 kcal/mol) showed affinity equivalent to anthocyanin. The t-test for all compounds yielded a value of 0.00 (<0.05), indicating strong statistical significance. The dominant interactions involve hydrogen and hydrophobic bonds at residues Cys285, Arg288, and Ile341, which act as partial agonists. ADME predictions indicate that the compounds have a fairly good pharmacokinetic profile in terms of metabolism and distribution, but face challenges in terms of absorption and excretion. Toxicity prediction results also indicate that all compounds are in the high category, and two of them are mutagenic. All anthocyanin compounds have potential as partial agonists/SPPARγM, especially Ternatin A2. However, due to limitations in absorption and excretion as well as toxicity, further studies related to structural modification and experimentation are needed to confirm the biological activity and safety of the compounds, as well as considering non-oral routes of administration..