Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in clinical trials and they have been classified according to their route or mechanism of action. Insulin types, sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, sodium–glucose cotransporter type 2 inhibitors, and incretin-dependent therapies (glucagon-like peptide-1 receptor agonists: GLP-1R, and dipeptidyl peptidase 4 inhibitors: DPP-4). Although some of the currently available drugs are effective in the management of T2DM, the side effects resulting from prolonged use of these drugs remain a serious challenge. GLP-1R agonists are currently the preferred medications to include when oral metformin alone is insufficient to manage T2DM. Medicinal plants now play prominent roles in the management of various diseases globally because they are readily available and affordable as well as having limited and transient side effects. Recently, studies have reported the ability of phytochemicals to activate glucagon-like peptide-1 receptor (GLP-1R), acting as an agonist just like the GLP-1R agonist with beneficial effects in the management of T2DM. Consequently, we propose that careful exploration of phytochemicals for the development of novel therapeutic candidates as GLP-1R agonists will be a welcome breakthrough in the management of T2DM and the co-morbidities associated with T2DM.

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.