Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Yam (Dioscorea sp.) extracts have been shown to possess a vast array of medicinal properties such as antihypocholesterolemic, antiatherogenic and antihypertensive bioactivity. However, the compounds conferring its antihypertensive bioactivity have not been fully explored. AIM OF THE STUDY: The objective of this study was to identify extractable bioactive fractions and associated compounds in Jamaican Renta Yam (Dioscorea alata) that contribute to its antihypertensive properties, using an activity driven chemoinformatic profiling method. MATERIALS AND METHODS: A diethyl ether extract of Dioscorea alata was obtained by sequential Solid-Liquid extraction coupled to SPE-HPLC fractionation and its chemical composition was analyzed by GC-MS analysis. Its influence on hypertension was evaluated through a combination of in vitro ACE-Inhibitory activity assays and by molecular docking of the identified compounds to the ACE enzyme. RESULTS: SLE revealed the presence of potent antihypertensive activity (ACE IC50 41.99 μg/mL) in the diethyl ether extract (DR2). GC-MS analysis of DR2 indicated the presence of small organic compounds (95.1 g/mol to 200 g/mol) with 2-Phenyl-1,3-oxazol-2-ine (2PO) being the most predominant small organic compound present in the bioactive extract. The binding affinity of 2PO was assessed using molecular docking of 2PO to the ACE enzyme and showed strong binding affinities forming two (2) hydrogen bonds with Tyr135 and Trp220 in the active site of the enzyme. The in vitro effect of DR2 using human umbilical vein endothelial cell lines (HUVECs) revealed; a significant dose-dependent ACE-Inhibitory activity, a stimulating of nitric oxide (NO) release and no toxicity towards these cells. CONCLUSION: Overall, this study identified Jamaican Renta Yam (Dioscorea alata) as an alternative source of antihypertensive compounds which may address the toxicity seen with known synthetic antihypertensive agents.