Antidiabetic effect of Saurauia bracteosa through GSK-۳β inhibition: Insights from phytochemical analysis, molecular docking, and glucose uptake in L۶ cells

Introduction: Saurauia bracteosa is a medicinal plant traditionally used by the Batak Toba and Karo ethnic groups of North Sumatra, Indonesia, to manage type ۲ diabetes mellitus (T۲DM). However, the precise molecular mechanisms responsible for its antidiabetic effect remain unclear. Thus, the purpose of this study was to investigate the mechanisms of action of S. bracteosa leaf extract and assess its potential in treating type ۲ diabetes. Methods: Phytochemical profiling was conducted using LC-MS/MS and GC-MS. Key active compounds, including ursolic acid and quercetin, were quantified by UPLC, and their effects on glucose uptake in L۶ skeletal muscle cells were evaluated. To learn more about possible molecular pathways, network pharmacology and molecular docking were used. Results: The extract was found to contain triterpenoids and flavonoids such as ursolic acid and quercetin, which significantly enhanced glucose uptake in L۶ cells with effects comparable to insulin (P>۰.۰۵). Network pharmacology identified multiple gene targets, with pathway enrichment analysis highlighting glycogen synthase kinase-۳ beta (GSK۳β) as a central protein. Molecular docking confirmed the strong binding affinity of quercetin to GSK۳β, supporting its potential role in modulating insulin signaling. Conclusion: These results suggest that GSK۳β regulation and enhanced glucose absorption in skeletal muscle cells may be involved in the antidiabetic action of S. bracteosa. This provides a scientific basis for its traditional use and highlights its potential for further development as a natural therapeutic option for diabetes.