Inhibition Mechanism of Berberine on α‐Amylase and α‐Glucosidase in Vitro

Abstract

Berberine is separated from medical plants and food raw materials, and shows excellent anti‐diabetic activity and could be used as a food additive in some countries and regions. However, its inhibitory mechanisms on α‐amylase and α‐glucosidase have hardly ever been revealed in vitro. In this study, enzymatic reaction kinetics, fluorescence quenching, circular dichroism spectroscopy, and molecular docking are used to study the inhibitory effects of berberine on α‐amylase and α‐glucosidase. Berberine has great inhibitory effects on α‐amylase and α‐glucosidase (IC50 = 50.83 µg mL–1, IC50 = 198.4 µg mL–1, respectively), and inhibition types of α‐amylase and α‐glucosidase are non‐competitive inhibition and competitive inhibition, respectively. Fluorescence spectra show that there is static quenching between berberine and α‐amylase or α‐glucosidase. Besides, hydrophobic interaction is the main interaction type. These results are further evidenced and visualized by molecular docking. This study provides a different theoretical basis for berberine in anti‐diabetic activity in vitro and expands interaction research about hydrophobic compounds and α‐amylase as well as α‐glucosidase.

Structure and Antidiabetic Activity of a Glycoprotein from Porphyra haitanensis

“…For example, Ile-79 on the α-subunit formed hydrophobic interactions with Tyr-252, Ala-253, and Ser-254 on the α-amylase, whereas Gln-11 on the β-subunit formed hydrogen bonds and hydrophobic interactions with Ile-127, Lys-128, and Trp-130 on the α-amylase (Figure b). It has been reported that hydrophobic interactions are an important pathway to inhibit α-amylase activity . These results suggested that PG affected the catalytic activity of key amino acid residues of α-amylase through hydrophobic action, formed hydrophobic pockets to alter the hydrophobic microenvironment of the enzyme, and then formed steric hindrances to inhibit the activity of the enzyme, which was consistent with the results of the fluorescence spectrum analysis.…”

“…3 The formation of hydrogen bonds resulted in increased hydrophobicity and decreased hydrophilicity of the inhibitor−enzyme complex. 51 It could be that the hydroxyl and hydrophobic amino acids in PG enhanced the hydrogen bonds and the hydrophobic interaction between PG and α-glucosidase, formed a PG− enzyme complex, changed the enzyme structure, and inhibited the enzyme activity, and the docking results were consistent with the results of the enzyme structure changes. An antidiabetic hydrophobic compound was also found to play a hypoglycemic role by altering the structure and active site of αamylase and α-glucosidase through the hydrophobic interaction.…”

“…An antidiabetic hydrophobic compound was also found to play a hypoglycemic role by altering the structure and active site of αamylase and α-glucosidase through the hydrophobic interaction. 51 In conclusion, PG altered the structure of α-amylase and α-glucosidase by hydrophobic action, α-helix structure, and O-glycosidic linkage, impeded the formation of the active site of the enzyme, and inhibited the enzyme activity, showing a promising hypoglycemic effect. For example, PG decreased the fluorescence intensity of α-amylase and α-glucosidase via a hydrophobic effect.…”

Purification, biochemical characterization, and DPP‐IV and α‐amylase inhibitory activity of Berberine from Cardiospermum halicacabum

“…As a result, slowing the rate of glucose absorption and lowering post‐prandial serum glucose levels by inhibiting enzymes such as α ‐amylase plays an important role in diabetes control. Several traditionally used plants have demonstrated α ‐amylase inhibitory activity in vitro and in vivo, 13,52 and in recent reports, berberine has been shown to inhibit α ‐amylase in a non‐competitive manner, suggesting a different theoretical basis for the anti‐diabetic potential of berberine and expanding interaction research about hydrophobic compounds 53 . Further docking experiments of amylase PDBID (2QV4) with berberine revealed that berberine bound to the active site with a binding energy of −7.9 kcal/mol, similar to known inhibitors like acarbose (Figure S6).…”

A Review of Fibraurea tinctoria and Its Component, Berberine, as an Antidiabetic and Antioxidant

“…A study conducted by Zhao et al showed that berberine has strong inhibitory activity against both α-amylase and α-glucosidase in vitro, with IC 50 values of 50.83 µg/mL and 198.40 µg/mL, respectively. The inhibition type in α-amylase is non-competitive, whereas, in α-glucosidase, competitive inhibition is observed [ 352 ]. In Caco-2 cells, berberine reduces glucose absorption in the gastrointestinal tract by inhibiting α-glucosidase activity [ 353 ].…”