Experimental and Computational Insights into Gangronema latifolium Leaf Compounds as GLP-1 Receptor Agonists

• Published in: Chemistry Africa Vol. 7; no. 5; pp. 2581 - 2597
• Main Authors: Duru, Ijeoma Akunna, Enenebeaku, Uchechi Emmanuela, Ngozi-Olehi, Lynda Chioma, Enyoh, Christian Ebere, Duru, Chidi Edbert, Umar, Haruna Isiyaku, Kuthi, Najwa Ahmad, Kumar, Neeraj, Dharmarpu, Vijay
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-07-2024
• Subjects: Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Inorganic Chemistry; Organometallic Chemistry; Original Article; Type 2 diabetes; Glucagon-like peptide 1 receptor; Stigmasterol; Campesterol
• ISSN: 2522-5758; 2522-5766
• DOI: 10.1007/s42250-024-00951-0

The International Diabetes Federation reported that in 2021, 6.7 million deaths globally were linked to diabetes. Ethnomedicinal and scientific reports abound on using the extract from the leaf of 
Gongronema latifolium
 in managing diabetic patients. This study used a wide range of computational methods to identify and validate hit compounds from 
G. latifolium
 crude leaf extract with the potential to activate the GLP-1 receptor. Molecular docking results showed that the binding affinity of the hit molecules campesterol (–7.5 kcal mol
−1
) and stigmasterol (–7.4 kcal mol
−1
) was very close to the control drug Glyburide (–7.9 kcal mol
−1
) at this target. ADMET analysis predicted that the properties of these compounds were within acceptable limits. Molecular dynamics simulation integrated with essential dynamics techniques, i.e., principal component analysis (PCA), dynamics cross-correlation maps (DCCM), and free energy landscape (FEL), as well as density functional theory (DFT) analysis at B3LYP/6-311 +  + G(2p,2d) level of theory, were further added to give depth to the computational analysis. The simulations offer a glimpse into how specific residues in the binding site of the GLP-1 receptor engage with stigmasterol, validating the stability and robust nature of the complex. The potent computational prognostications reinforce the confidence in the therapeutic potential of stigmasterol as a GLP-1 receptor agonist, fueling enthusiasm for their exploration in both in vitro and in vivo contexts.