Abstract:
Background: Diabetes mellitus (DM) is considered as one of the fastest-rising chronic metabolic
diseases. Medicinal plants and their isolated compounds demonstrate multiple therapeutic benefits
against DM. Gymnema sylvestre R. Br. (Gurmar, Asclepiadaceae) and Trigonella foenum
graceum L. (Fenugreek, Fabaceae) are such medicinal plants with proven antidiabetic activity.
Objective: To analyze phytochemical-target protein interactions via molecular dynamic
simulations and validation of findings using in vitro anti-diabetic assays
Methods: This study employed constructing a 221-compound library from G. sylvestre and T.
foenum-graceum for virtual screening against α-amylase and α-glucosidase target proteins.
Bioinformatic tools facilitated virtual screening, molecular dynamics simulations and ADMETox
analysis. The α-amylase and α-glucosidase inhibitory potentials were assessed using 50% EtOH
extracts of G. sylvestre leaves and T. foenum-graceum seeds with acarbose as the reference
compound. Total phenolic content (TPC) and total flavonoid content (TFC) were estimated using
Folin Ciocalteu and aluminum chloride methods, respectively. In-vitro assay results are expressed
as mean±SD, analysed using One-way ANOVA with post hoc Tukey’s test.
Results: Trigoneoside XIIa (-9.1 kcal/mol), trigofoenoside G (-9.8 kcal/mol) in T. foenum
graceum and gymnemasaponin v (-9.7 kcal/mol) in G. sylvestre had the most stable binding
interaction with the target proteins based in-silico studies conducted using the compound library.
In-vitro assays further revealed that T. foenum-graceum seed extract showed the highest α
amylase inhibition (IC50 = 12.09±2.13 mg/mL) and α-glucosidase inhibition (IC50 = 5.23±0.33
mg/mL). Acarbose exhibited IC50 values of 0.0045±0.0002 mg/mL for α-amylase and 1.8±0.61
mg/mL for α-glucosidase. G. sylvestre leaf extract had the highest TPC (19.042±0.153 mg GAE/g)
and TFC (12.862±0.761 mg Quercetin/g). Significant differences in α-amylase and α-glucosidase
inhibition were observed among all plant extracts compared to acarbose (p<0.05).
Conclusions: Trigoneoside XIIa, trigofoenoside G, and gymnemasaponin v were identified as
promising candidates for managing diabetes mellitus. Based on the results, 50% EtOH T. foenum
graceum seed extract was found as an effective α-amylase and α-glucosidase inhibitor.
