An experimental and computational approach to evaluate the antidiabetic activity of Commiphora wightii gum extract.

Background: Plant formulations with antidiabetic and antioxidant properties have recently gained popularity due to their lower cost and lesser side effects. Guggul gum is one such formulation that is extensively being used to cure various ailments.

Objective: The present study was designed to explore the antioxidant and antidiabetic properties of the aqua-ethanolic Guggul gum extract (GE) from Commiphora wightii using in silico studies and in vitro assays.

Methods: Gas Chromatography Mass Spectroscopy (GCMS) identified compounds were docked to the Human pancreatic α-amylase (HPA, PDB ID: 1HNY) for in silico studies to predict the inhibition. Molecular dynamics simulations (MDS) were performed using GROMACS for 100 ns. The inhibition of the enzyme was further evaluated at in vitro level to show the compounds' hypoglycemic role.

Results: The extract showed a good amount of phenolic (5.14 ± 0.011 mg), flavonoid (0.66 ± 0.023 mg) and terpenoid (1.08 ± 0.018 mg) content along with a promising free radical scavenging activity of 41.96 ± 4.02%. In the in silico studies, 3 out of 6 GCMS-identified bioactive compounds showed permissible values of bioavailability properties suggesting them as a potential candidate for antidiabetic drugs. Similarly, in molecular docking studies, 3 compounds showed more binding energy than the standard drug acarbose indicating better inhibition. MDS studies showed Compound 4 (Diisooctyl phthalate), was the most stable with the lowest root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values, a consistent radius of gyration (Rg), and stable solvent accessible surface area (SASA). This was further confirmed by in vitro analysis where the pancreatic α-amylase inhibitory activity of the extract and the standard drug (acarbose) were comparable at an IC₅₀ value of 4.17 ± 1.26 mg/mL and 3.69 ± 0.89 mg/mL respectively.

Conclusion: The results demonstrated GE as a potential alternative to commercial antidiabetic drugs. Out of the major 6 GCMS-identified compounds, Compound 4 showed the most stable conformation during MDS studies. However, the isolation of the identified compounds could be done in the future for in vivo studies.