In Silico Evaluation of Trigonelline Reported in Suaeda Baccata As a Potential Antidiabetic Compound: Molecular Docking, Dynamics and Binding Free-Energy Analysis Against Gsk-3β, Ampk Β1, And Dpp-4
Year: 2026
Type: article
Abstract: Objective: Diabetes mellitus (DM) is a long-term metabolic disorder that affects a high percentage of people around the world and continues to be a major public health issue. There is growing interest in natural products as affordable options for managing diabetes. Suaeda baccata is reported to contain trigonelline, an alkaloid known for its antidiabetic effects, but the molecular targets of trigonelline remain poorly understood. This study looked at how trigonelline might interact with glycogen synthase kinase-3β (GSK-3β), AMP-activated protein kinase β1 (AMPK β1), and dipeptidyl peptidase-4 (DPP-4). Methods: The physicochemical, pharmacokinetic, and toxicity properties of trigonelline were assessed using computational tools. Molecular docking was performed using metformin and sitagliptin as reference drugs, followed by a single exploratory 200-ns molecular dynamics simulation and MM-GBSA binding free-energy calculations. Results: Trigonelline was predicted to have good physicochemical and pharmacokinetic properties, including high gastrointestinal absorption, and showed no signs of toxicity in the tests. Docking results showed that trigonelline and metformin had similar binding scores for GSK-3β and AMPK β1, but trigonelline had weaker predicted binding to DPP-4 compared to sitagliptin. In the 200-ns simulations, the AMPK β1–trigonelline complex was the most stable, while the GSK-3β–trigonelline complex changed shape and did not stabilize. MM-GBSA analysis found binding free energies close to zero for trigonelline with all three targets, suggesting weak support for these bindings. Conclusion: Although molecular docking suggested possible interactions of trigonelline with the investigated targets, the MM-GBSA results did not support strong binding under the conditions tested. The AMPK β1–trigonelline complex showed the most stable behavior during the exploratory simulation, but this does not confirm strong binding or functional activation. Further independent simulations and testing studies are needed to confirm these results.
Institution: Al-Zahrawi University
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7225564610