In vitro and in silico synergistic antidiabetic effectiveness of several multi-drug combinations of Siraitia grosvenorii, Dimocarpus longan Lour., and Orthosiphon stamineus Benth. Extracts.

Considering the economic challenges associated with diabetes mellitus, it is essential to explore the viability of common dietary sources as supplementary remedies for individuals with diabetes. The current study is crafted to evaluate the combined extracts from Siraitia grosvenorii , Dimocarpus longan , and Orthosiphon stamineus for their synergistic antidiabetic effects using both in silico and in vitro methods. These assessments include DPPH (2,2-Diphenyl-1-picrylhydrazyl) radical scavenging capacity, α-amylase inhibition, α-glucosidase inhibition, DPP-4 inhibition, cytotoxicity, and glucose uptake kinetics. The combined formulation of S. grosvenorii , Dimocarpus longan and O. stamineus ( SG + DL + OS ) demonstrated promising DPPH inhibition with an IC 50 value of 9.11 ± 0.63 mg/mL. Moreover, it had inhibitory effects on α-amylase, α-glucosidase, and DPP-4 enzymes, with IC 50 values of 8.63 ± 0.35 mg/mL, 10.21 ± 0.13 mg/mL, and 12.01 ± 0.31 mg/mL, respectively. Moreover, a notable increase ( P < 0.05) in glucose uptake by L6 myoblasts was observed with the administration of various combinations. In silico analysis, which includes XP (extra-precision) docking and MM-GBSA (Molecular Mechanics, General Born Surface Area), revealed that 13 and 30 compounds within the combination exhibited substantial interactions and stable binding capabilities with α-amylase and DPP-4 proteins, signifying their potential as inhibitors for these enzymes. Consequently, it can be inferred that the combinations of S. grosvenorii , D. longan , and O. stamineus represent a promising therapeutic approach for diabetes management. • The combination of SG + DL + OS exhibited increased enzyme inhibitory activity. • The combination of SG + DL + OS has a significant impact on increasing glucose uptake. • The combination of SG + DL + OS contain components that inhibit α-amylase and DPP-4 enzymes.