Probing the mechanisms of flavonoids in corn silk for treating type 2 diabetes by in Silico and in vitro experiments

Corn silk, as a pure natural medicinal ingredient, has been used in many traditional Chinese medicine prescriptions for treating diabetes. Although corn silk has been proven to have anti-diabetic potential, the mechanism of action of the contained compounds on disease targets is still unclear. This study used network pharmacology to find that the main substances in corn silk for the treatment of type 2 diabetes are two flavonoids-chrysoeriol and luteolin. These two compounds mainly inhibit the target DPP4 activity, so we used the DPP4 inhibitor Sitagliptin as a positive experimental drug and verified their mechanism of action and safety through molecular docking, molecular dynamics simulation, and in vitro experiments. Molecular docking results showed that the docking energies of luteolin and chrysoeriol with DPP4 protein were - 7.44 kcal/mol and - 6.35 kcal/mol, respectively. This result was slightly lower than the docking energy of the positive control drug sitagliptin with DPP4 protein, but more hydrogen bonds were produced. A series of results of molecular dynamics simulation showed that luteolin and chrysoeriol could form a stable complex system with the target protein. In vitro experiments showed that high concentrations of luteolin and chrysoeriol (100 µg/ml) only caused about 20% damage to the three normal cell types (L929, HEK293, MIN6). The inhibition rates of luteolin and chrysoeriol on DPP4 protein were 76.22% and 78.45%, respectively. Although this result was lower than the 88.88% inhibition rate of sitagliptin as an inhibitor, it proved that these two compounds played a positive role in the inhibition of DPP4 protein. The above in silico results prove that the main components of corn silk can form a stable complex system with the DPP4 target protein of type 2 diabetes. The MTT experiment proves that corn silk extract has reliable safety in the treatment of diabetes, and the experimental results of the DPP4 inhibitor kit more intuitively prove the significant role of corn silk in the treatment of type 2 diabetes. Therefore, the bioactive substances extracted from corn silk have anti-diabetic potential and can be used in future research and development of novel anti-diabetic drugs.