Abstract

Background: Abutilon indicum (L.) Sweet (Malvaceae) is a traditional medicinal plant known for its antidiabetic properties in Ayurveda and other health systems. Aims: This study aims to profile metabolites in Abutilon indicum (L.) Sweet extracts (AI) and elucidate their antidiabetic mechanisms through bioinformatics and experimental methods. Study Design: The ethanolic (AIE) and aqueous (AIA) extracts were evaluated for their inhibitory effects on α-glucosidase and α-amylase, as well as their impact on glucose metabolism in 3T3-L1 adipocytes and L6 skeletal muscle cells. AIE was characterized via HPLC-DAD-QTOF-MS, with network pharmacology and molecular docking analyses used to explore molecular targets. Methods: In vitro assays were performed to assess enzyme inhibition, and cell line studies HPLC-DAD-QTOF-MS were utilized for compound characterization. Network pharmacology and molecular docking were conducted to reveal underlying antidiabetic mechanisms. Results: LC-MS-QTOF analysis identified gallic acid, stigmasterol, and riboflavin as abundant compounds. The AIE exhibited significant α-glucosidase (IC<inf>50</inf> = 74.15 ± 1.61 μg/mL) and α-amylase inhibition (IC<inf>50</inf> = 13.41 ± 0.71 μg/mL). Moreover, it enhanced glucose consumption in 3T3-L1 cells (IC<inf>50</inf> = 6.25 μg/mL) and promoted glucose uptake in L6 myotubes. Network pharmacology analyses highlighted the PI3K–Akt signaling pathway’s role in facilitating glucose transport. Conclusion: The phytochemicals in AIE may contribute significantly to its antidiabetic effects, particularly through the modulation of glucose transport via the PI3K–Akt pathway. Future studies should focus on the preclinical development of safe herbal formulations utilizing these mechanisms for effective diabetes management.