Corn silk extracts modulated ADORA1 and GABBR1 for type 2 diabetes mellitus intervention: An in vitro validation study

While in silico antidiabetic mechanism of corn silk (CS) has been established, studies validating this activity in biological system is lacking. This study validates the antidiabetic potential of premature and mature CS extracts in HepG2 cells with a focus on previously identified adenosine receptor A1 (ADORA1) and gamma-aminobutyric acid type B subunit 1 (GABBR1) genes of cyclic adenosine monophosphate pathway. At 75 – 100 µg/mL, ethanolic extract of the mature CS (75 µg/mL) showed enhanced HepG2 cells viability than normal (untreated), positive controls (insulin and metformin) and other extracts treated cells. In the glucose uptake assay, the highest uptake relative to the normal (7.38 mmol/L) cells was noted in aqueous extract of mature CS-treated insulin-resistant HepG2 (IR-HepG2) cells (4.13 mmol/L). A further probe into the modulatory effect of the extracts at their optimal doses on the expression of the profiled genes revealed that the aqueous extract of the premature CS (100 µg/mL) proficiently downregulated the expression of ADORA1 and GABBR1 in IR-HepG2 cells relative to the controls. These observations with the extract could be associated with its high abundance of gallicynoic acid B and tetradecanedioc acid previously identified as effective modulators of ADORA1 and GABBR1, respectively. The findings of this study not only suggest the possible mechanism of antidiabetic action of CS in HepG2 cells through the modulation of ADORA1 and GABBR1 for increased glucose uptake but will contribute towards the development of CS as an antidiabetic agent.