Diabetes mellitus type 2 (T2DM) is a health concern that continues to threaten the world, which is why there is a need to explore natural antidiabetic agents. Earlier research has clearly indicated the roles of α-amylase and α-glucosidase in carbohydrate metabolism, and their inhibition can be used as therapeutic agents. This study aimed to determine the antidiabetic activity of the hydroalcoholic extract of the Canarium odontophyllum Miq fruit (COFE) and its extracted flavonoid, 3,5,7,2′,5′-pentahydroxyflavone, using an in vitro and in silico approach. In it, isolates of COFE and isolated flavonoid were evaluated as inhibitors of these enzymes by standard in vitro assays. Meanwhile, we performed molecular docking experiments to clarify the binding interactions with the enzyme's active sites. The findings revealed a moderate inhibitory effect of COFE with IC 50 values of 10.36 mg/mL for α-amylase and 7.62 mg/mL for α-glucosidase. Isolated flavonoids showed stronger α-amylase inhibition (IC 50 = 3.93 mg/mL), which was probably because of numerous hydroxyl groups that increased binding affinity. Conversely, the flavonoid and COFE had similar α-glucosidase inhibition (IC 50 = 7.40 mg/mL). Acarbose, the positive control, was more effective, with IC 50 values of 0.59 and 0.44 mg/mL for -amylase and -glucosidase inhibition, respectively. Molecular docking experiments indicated that the isolated flavonoid exhibited greater binding affinity and specific interactions with key catalytic residues, thereby contributing to its potential as an inhibitor. Conclusively, the combination of experimental and computational data highlights the therapeutic potential of COFE and its flavonoid component as natural antidiabetic compounds. In vivo research and pharmacokinetic analyses are warranted to further evaluate these findings in clinical practice and the development of plant-based diabetes treatment. • Canarium odontophyllum fruit extract and its isolated flavonoid, 3,5,7,2′,5′-pentahydroxyflavone, exhibited significant in vitro inhibition of α-amylase and α-glucosidase. • The isolated flavonoid showed more potent α-amylase inhibition (IC₅₀ = 3.93 mg/mL) than the crude extract, highlighting its role as the principal bioactive agent. • Molecular docking revealed a high binding affinity of the flavonoid to both enzyme active sites, surpassing acarbose in predicted binding energy. • Integration of in vitro and in silico approaches provided a comprehensive mechanistic understanding of the antidiabetic effects of the extract and flavonoid. • The findings support the therapeutic potential of C. odontophyllum and its flavonoid as plant-based antidiabetic agents, warranting further in vivo studies.
Siang et al. (Wed,) studied this question.