Screening and functional evaluation of the glucose-lowering active compounds of total saponins of Baibiandou (Lablab Semen Album)

Objective

To screen for α-glucosidase inhibitor active compounds in the total saponins of Baibiandou (Lablab Semen Album) based on UHPLC-Q-Exactive Orbitrap MS technology and to evaluate its hypoglycemic activity in vivo.

Methods

Acarbose was used as the positive control, and the median inhibitory concentration (IC₅₀) was used as the evaluation index of α-glucosidase inhibitory activity to establish an in vitro α-glucosidase inhibition model. Further, UHPLC-Q-Exactive Orbitrap MS technology was used to screen and identify the active compounds of α-glucosidase inhibitors in the total saponins of Baibiandou (Lablab Semen Album) in order to further verify the activity of the main active monomer and to perform homologous modeling and molecular docking of yeast-derived α-glucosidase and human-derived α-glucosidase, while the hypoglycemic activity was evaluated in diabetic mice.

Results

This study successfully identified 15 compounds with potential α-glucosidase inhibitory activity, including Chikusetsusaponin IVa, from the total saponins of Baibiandou (Lablab Semen Album). Simultaneously, we verified the activity of the main active monomer Chikusetsusaponin IVa, and showed that it has strong α-glucosidase inhibitory activity. The α-glucosidase inhibitory concentration IC₅₀ was (565.2 ± 1.026) μg/mL, and the IC₅₀ of acarbose, which was lower than the positive control, was (706.6 ± 1.058) μg/mL. The docking energies of Chikusetsusaponin IVa were – 6.1 and – 7.7 kcal/mol with yeast-derived α-glucosidase and human-derived α-glucosidase molecules, respectively. Both showed strong binding activity, and the levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), UREA, Creatinine (CREA), and cholesterol (CHO) were significantly decreased by Chikusetsusaponin IVa (P < 0.05). In addition, it could repair damaged liver and pancreas cells of diabetic mice to some extent.

Conclusion

This study provides a basis for screening α-glucosidase inhibitors and structural modifications of the total saponins of Baibiandou (Lablab Semen Album).