Sphenocentrum jollyanum furanoditerpenes activates Glucagon-like peptide 1 receptor (GLP-1R): a computational evaluation

Sphenocentrum jollyanum is a major bio-resource used in the folkloric treatment of diabetes, unfortunately without knowledge of how or the mechanism of action. The present study focuses on using molecular docking to identify the component responsible for the anti-diabetic claim of the fruit as well as check the ADMET properties of the phytochemicals. A library of 23 phytochemicals that have been previously characterized from Sphenocentrum jollyanum fruit was generated and docked, using Autodock Vina, into 3D structures of dual-specificity tyrosine phosphorylation regulated kinase 1a (DYRK1A), peroxisome proliferator-activated receptor alpha (PPAR-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), pancreatic alpha-amylase, dipeptidyl peptidase 4 (DPP4), glucagon-like peptide 1 receptor (GLP-1R), renal sodium-dependent glucose transporter (SGLUT 2). From the docking result, GLP-1R was identified as a major target for two key S. jollyanum furanoditerpenes (columbin and isocolumbin) with docking scores of -10.7 and -10.9 Kcal/mol respectively while the reference ligand (danuglipron) characterized with the GLP-1R had a score of -11.0 Kcal/mol. The protein-ligand interaction between columbin and GLP-1R showed several interactions such as hydrogen bond (H-bond), hydrophobic interactions and salt bridges, all within the extracellular domain (ECD), transmembrane domain (TM) of the receptor which is similar to that of danuglipron. Also, the ADMET profiling result was favourable as both ligands (columbin and isocolumbin) passed the Lipinski rule of 5. The results suggest that columbin identified from the docking result is most likely responsible for the antidiabetic claim of Sphenocentrum jollyanum, further investigation is needed to ascertain this claim.