An Integrated In Silico and In Vitro Assays of Dipeptidyl Peptidase-4 and α-Glucosidase Inhibition by Stellasterol from Ganoderma australe

Background: <i>Ganoderma</i> fungus is rich in terpenoids. These compounds are known for their anti-hyperglycemic activities. However, the study of terpenoids as the secondary metabolite from <i>Ganoderma</i> as a dipeptidyl peptidase-4 (DPP-4) inhibitor remains unexplored. In addition, we examined the &#945;-glucosidase inhibition activity. Objective: This study aimed to isolate the major terpenoid from non-laccate <i>Ganoderma</i> and examined its inhibitor activity on DPP-4 and &#945;-glucosidase enzymes, and its interaction. Methods: The compound was isolated using column chromatography from <i>Ganoderma australe</i>. The structure of the isolated compound was confirmed by ¹H and ¹³C nuclear magnetic resonance spectroscopy, while the inhibitory activity was evaluated using an enzymatic assay. The interaction of the isolated compound with DPP-4 and &#945;-glucosidase enzymes was investigated using an in silico study. Results: The isolated compound was identified as stellasterol; IC₅₀ values for DPP-4 and &#945;-glucosidase inhibitor were 427.39 &#181;M and 314.54 &#181;M, respectively. This study revealed that the inhibitory effect of stellasterol on DPP-4 enzyme is through hydrophobic interaction, while the &#945;-glucosidase enzyme is due to the interaction with six amino acids of the enzyme. Conclusion: Stellasterol is the major component of the steroid from <i>G. australe</i>. Enzyme inhibitory assay and in silico study suggest that stellasterol may contribute antidiabetic activity with a mechanism closer to acarbose rather than to sitagliptin.

Abstract licence: CC BY

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