Speakers - DEWC2025

Abstract

Pancreatic beta cell dysfunction is a hallmark of diabetes, and targeting pathways regulating their differentiation holds promise for novel therapies. This study aims to investigate the role of cannabinoids from Cannabis sativa in pancreatic beta cell differentiation via the WNT5A/JNK and BMP pathways using an in silico approach. The molecular docking simulations are used to predict the binding affinity and molecular interactions of six cannabinoids with key proteins involved in the WNT5A/JNK (WNT5A, JNK, c-JUN, and FZD3) and BMP (BMP6, SMAD 1, 4 and 5) pathways. The stability and accuracy of the protein-ligand complexes obtained from molecular docking simulations were validated using RMSD values, and normal mode analysis was conducted to gain insights into molecular flexibility and deformation. RMSD analysis validated the stability of predicted binding modes, and normal mode analysis was conducted to gain insights into molecular flexibility and deformation. The molecular docking results showed that all six cannabinoids had binding affinities with proteins involved in the WNT5A/JNK and BMP pathways, with the highest affinity observed for the JNK-Cannabinol and SMAD4- tetrahydrocannabivarin complex. The RMSD values validated the accuracy and stability of the protein-ligand complexes. Specific interactions, such as hydrophobic contacts and hydrogen bonds, were identified between JNK-Cannabinol and SMAD4- tetrahydrocannabivarin. Normal mode analysis revealed flexible and rigid regions within the complexes that could impact interaction surfaces. The findings of this study suggest that cannabinoids may directly impact beta cell differentiation signaling cascades and warrant further investigation into their potential as anti-diabetic agents.