In vitro Anti-diabetic Activity of Selected Medicinal Plant Extracts: A Comparison with in-silico Studies.

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.