BuZhong YiQi Formula Alleviates Postprandial Hyperglycemia in T2DM Rats by Inhibiting α-Amylase and α-Glucosidase In Vitro and In Vivo

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Abstract
Background/Objectives: BuZhong YiQi Formula (BZYQF) can alleviate type 2 diabetes mellitus (T2DM). However, its efficacy in managing postprandial hyperglycemia in T2DM needs to be further confirmed, and its underlying mechanism and pharmacodynamic material basis have not been sufficiently investigated. Methods: A T2DM rat model was induced to measure postprandial glycemic responses following glucose and starch ingestion. In vitro assays of enzymatic inhibition and the kinetic mode were performed to evaluate the inhibitory effect of BZYQF on α-amylase and α-glucosidase activities. The main constituent contents of BZYQF in a simulated digestion assay were measured to screen the active constituents in BZYQF against α-amylase and α-glucosidase activities via Pearson correlation and multiple linear regression analyses. Finally, the total flavonoids were purified from BZYQF to perform in vitro activity validation, and the flavonoid constituent activity was verified through molecular docking. Results: In vivo assays showed that BZYQF significantly reduced the blood glucose values of CON rats but not T2DM rats after glucose ingestion, while BZYQF significantly reduced the blood glucose levels by 15 min after starch ingestion in CON and T2DM rats, with more significant decreases in blood glucose levels in T2DM rats. In vitro enzymatic assays showed that BZYQF could inhibit the activities of α-amylase and α-glucosidase in competitive and non-competitive modes and in an uncompetitive mode, respectively. Furthermore, BZYQF showed a stronger inhibitory effect on α-glucosidase activity than on α-amylase activity. Simulated digestion showed that simulated gastric fluid and intestinal fluid changed the main constituent contents of BZYQF and their inhibition rates against α-amylase and α-glucosidase activities, and similar results were rarely found in simulated salivary fluid. Pearson correlation and multiple linear regression analyses revealed that the total flavonoids were the active constituents in BZYQF inhibiting α-amylase and α-glycosidase activities. This result was verified by examining the total flavonoids purified from BZYQF. A total of 1909 compounds were identified in BZYQF using UPLC-MS/MS, among which flavones were the most abundant and consisted of 467 flavonoids. Molecular docking showed that flavonoids in BZYQF were bound to the active site of α-amylase, while they were bound to the inactive site of α-glucosidase. This result supported the results of the enzyme kinetic assay. Conclusions: BZYQF significantly alleviated postprandial hyperglycemia in T2DM rats by inhibiting α-amylase and α-glycosidase activities, in which flavonoids in BZYQF were the active constituents.
Funding Information
  • National Natural Science Foundation of China (82174105, 81102703, 2017A030313837, 2013A032500005, 202410573003)
  • Natural Science Foundation of Guangdong Province (82174105, 81102703, 2017A030313837, 2013A032500005, 202410573003)
  • Science and Technology Planning Project of Guangdong Province (82174105, 81102703, 2017A030313837, 2013A032500005, 202410573003)
  • College Student Innovation Training Program in China (82174105, 81102703, 2017A030313837, 2013A032500005, 202410573003)

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