Cordyceps militaris Inhibited Angiotensin-Converting Enzyme through Molecular Interaction between Cordycepin and ACE C-Domain.

Abstract

One of the most important therapeutic modalities for the management of hypertension is the inhibition of the angiotensin-converting enzyme (ACE). Cordyceps militaris has received substantial attention because to its therapeutic potential and biological value. To gather information about the antihypertensive properties of C. militaris, the ACE inhibitory activity was evaluated. An ethanolic extract of the fruiting body of C. militaris was obtained, and the extract was separated by UHPLC method with a fluorescence detector for the quantification of cordycepin and adenosine. The ethanolic extract had a considerably higher cordycepin level. Additionally, an in vitro kinetic analysis was carried out to find out how much C. militaris extract inhibited ACE. This extract exhibited non-competitive inhibition on ACE. The Ki value of the C. militaris extract against ACE was found to be 8.7 µg/mL. To the best of our knowledge, this is the first report of the analysis of a protein cavity together with molecular docking carried out to comprehend the intermolecular interactions between cordycepin and the ACE C-domain, which impact the spatial conformation of the enzyme and reduce its capacity to break down the substrate. According to a molecular docking, hydrogen bonding interactions between the chemicals and the ACE S2’ subsite are primarily responsible for cordycepin inhibition at the ACE C domain. All these findings suggest that C. militaris extract are a kind of natural ACE inhibitor, and cordycepin has the potential as an ACE inhibitor.