Protopine as a multitarget modulator of glucose homeostasis: An in silico approach

Protopine is a benzylisoquinoline alkaloid found in several Papaveraceae species with known anti-inflammatory and neuroprotective effects [ 1 ]. However, its potential as an antidiabetic agent remains underexplored. This study aimed to evaluate the interaction profile of protopine with multiple key proteins involved in glucose homeostasis using in silico molecular docking. Docking simulations were conducted on eight diabetes-related protein targets: PPARγ (2PRG), AMPK (5ISO), α-glucosidase (3TOP), PTP1B (1T49), insulin receptor kinase (1IRK), GSK-3ββ.1), suggesting a potential role in modulating both insulin signaling and incretin pathways, which are clinically targeted by GLP-1 receptor agonists in diabetes treatment ([ Fig. 1 ]). Strong interactions were also observed with PPARγ, α-glucosidase, and AMPK, supporting a multifaceted mechanism that may involve enhanced insulin sensitivity, inhibition of glucose absorption, and improved energy metabolism [ 3 ]. These preliminary findings highlight protopine as a possible lead compound for further pharmacological investigation in the context of type 2 diabetes, although these values should be interpreted with caution due to limitations of in silico scoring functions. Further in vitro and in vivo studies are needed to validate its therapeutic potential [ 2 ]. Fig. 1 Molecular docking visualization of protopine bound to key antidiabetic target proteins. (a) Binding pose of protopine in the active site of AKT1 (PDB ID: 3O96). (b) Binding interaction of protopine with GSK-3β (PDB ID: 1Q5K). (c) Binding conformation of protopine at the GLP-1 receptor site (PDB ID: 6LN2) Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany