This study aims to identify and isolate the secondary metabolites of Zingiber officinale using GC-MS, preparative TLC, and LC-MS/MS methods, to evaluate the inhibitory potency on SARS-CoV-2 3 chymotrypsin-like protease enzyme, as well as to study the molecular interaction and stability by using docking and molecular dynamics simulations. GC-MS analysis suggested for the isolation of terpenoids compounds as major compounds on methanol extract of pseudostems and rhizomes. Isolation and LC-MS/MS analysis identified 5-hydro-7, 8, 2′-trimethoxyflavanone (9), (E)-hexadecyl-ferulate (1), isocyperol (2), N-isobutyl-(2E,4E)-octadecadienamide (3), and nootkatone (4) from the rhizome extract, as well as from the leaves extract with the absence of 9. Three known steroid compounds, i.e., spinasterone (7), spinasterol (8), and 24-methylcholesta-7-en-3β-on (6), were further identified from the pseudostem extract. Molecular docking showed that steroids compounds 7, 8, and 6 have lower predictive binding energies (MMGBSA) than other metabolites with binding energy of −87.91, −78.11, and −68.80 kcal/mole, respectively. Further characterization on the single isolated compound by NMR showed that 6 was identified and possessed 75% inhibitory activity on SARS-CoV-2 3CL protease enzyme that was slightly different with the positive control GC376 (77%). MD simulations showed the complex stability with compound 6 during 100 ns simulation time.

Englerophytum magalismontanum, a medicinal plant with ethnopharmacology use, has a dearth of information regarding its antidiabetic properties. This study evaluated the crude methanol leaf extract of E. magalismontanum and its fractions for total phenolic content, antioxidant activity, and digestive enzymes (α-amylase and α-glucosidase) inhibitory activity using standard methods. The total phenolic content (56.53 ± 1.94 mg GAE/g dry extract) and DPPH Trolox antioxidant equivalent (TAE) (1.51 ± 0.66 µg/mL) of the methanol fraction were the highest among the fractions. The IC₅₀ values of the methanol fraction against α-amylase (10.76 ± 1.33 µg/mL) and α-glucosidase (12.25 ± 1.05 µg/mL) activities were also high. Being the most active, the methanol fraction was subjected to bio-assay guided column chromatography-based enzyme inhibition to obtain a pure compound. The phenolic compound isolated and identified as naringenin inhibited α-amylase and α-glucosidase with IC₅₀ of 5.81 ± 2.14 µg/mL and 4.77 ± 2.99 µg/mL, respectively. This is the first study to isolate naringenin from E. magalismontanum extract. The molecular docking and molecular dynamics studies demonstrated naringenin as a promising lead compound in comparison to acarbose for the treatment of diabetes through the inhibition of α-glucosidase activity.

Diabetes is a degenerative disease affecting many people in Indonesia, where herbal preparations offer an alternative treatment. This study aims to identify potential antidiabetic drugs from four ethnopharmacological plants of Sulawesi (Cordia myxa L., Syzygium cumini, Syzygium malaccense, and Antidesma bunius) using network pharmacology and molecular docking approaches. Secondary metabolites in the ethanolic extracts were identified using gas chromatography-mass spectrophotometry (GC-MS), followed by analysis of potential antidiabetic targets through network pharmacology and docking studies with Molecular Operating Environment (MOE) software. Network pharmacology revealed PPARG as a potential target for C. myxa and GCG receptors for the other plants. Docking analysis showed that C. myxa compounds bind strongly to PPARG (PDB ID: 5YCP), surpassing Rosiglitazone (-7.49635 kcal/mol), with top binding energies observed for Squalane (-9.6078 kcal/mol), 2,6,10,14,18,22-Tetracosahexaene, 2,6,10,15,19,23-hexamethyl-(all-E)- (-8.7069 kcal/mol), and Anodendroside G monoacetate (-8.0845 kcal/mol). Meanwhile, for GCG (PDB ID: 5EE7) receptor interactions, several compounds demonstrated stronger binding than MK-0893 (-5.66941 kcal/mol). A. bunius exhibited the highest GCG binding affinities from terpenoid of 2,5,7,8-Tetramethyl-2-(4,8,12-Trimethyltridecyl)-3,4-Dihydro-2h-Chromen-6-Yl Hexofuranoside (-8.8001 kcal/mol), while S. malaccense and S. cumini compounds showed moderate to strong binding energies ranging from -7.6398 to -6.5939 kcal/mol. These findings highlight the significant antidiabetic potential of C. myxa targeting PPARG and A. bunius, S.malaccense and S.cumini targeting GCG receptors, offering promising candidates for antidiabetic drug development.