α-amylase Inhibitor Based on Oleanolic Acid: In vitro and in silico Studies

Alpha-amylase (α-amylase) is a key enzyme involved in the hydrolysis of α-1,4-glycosidic bonds in starch, playing a crucial role in regulating carbohydrate metabolism. Inhibiting the activity of α-amylase is a promising therapeutic approach for managing disorders associated with abnormal glucose metabolism, such as diabetes and obesity. Oleanolic acid (OA), a common pentacyclic triterpenoid found in various natural plants, exhibits a wide range of pharmacological properties, including hepatoprotective, anti-inflammatory, antioxidant, and potential anticancer effects. This study investigates the α-amylase inhibitory activity of OA derived from Panax bipinnatifidus Seem. cultivated in Vietnam using a combined in vitro and in silico approach. In the in vitro assays, OA exhibited α-amylase inhibitory activity with an IC50 value of 190.84 μg/mL; however, it was less effective compared to acarbose, a reference inhibitor with an IC50 value of 14.15 μg/mL. In contrast, in silico studies utilizing molecular docking shed light on the detailed molecular interactions between oleanolic acid and α-amylase. Key amino acid residues involved in the binding process include TYR62, ASP197, GLU233, HIS101, and LEU162, forming hydrogen bonds and hydrophobic interactions with OA. The calculated binding energy was -8.33 kcal/mol-1, indicating strong affinity and stable binding between OA and α-amylase. When compared to acarbose, OA displayed a stronger binding affinity to α-amylase, while acarbose had a binding energy of -2.90 kcal/mol-1. However, acarbose formed more hydrogen bonds with various amino acid residues such as GLU233, ASP300, GLY304, HIS305, and GLY306, along with van der Waals interactions, indicating a distinct binding pattern compared to OA. These results suggest that although OA has potential as a natural α-amylase inhibitor, its efficacy remains lower than acarbose in both molecular simulations (in silico) and experimental assays (in vitro). This underscores the necessity to optimize the structure of OA or combine it with other therapeutic strategies to enhance its α-amylase inhibitory effectiveness, while also opening avenues for further research into natural α-amylase inhibitors.