Uji In Silico Hasil LC-HRMS dari Ekstrak Etanol Batang Bakau Api-Api (Avicennia marina) sebagai Inhibitor Angiotensin Converting Enzyme (ACE)

Abstract

Background: : Hypertension is the leading cause of death worldwide each year and is categorized as a deadly disease, often referred to as a “silent killer.” The Angiotensin-Converting Enzyme (ACE) receptor plays a crucial role in regulating blood pressure through the renin-angiotensin-aldosterone system (RAAS). The metabolite content of the ethanol extract of the Api-Api mangrove stem (Avicennia marina) is predicted to exhibit antihypertensive activity through ACE inhibition. Objective: This study aims to predict the activity of metabolites from the ethanol extract of Avicennia marina stem as an antihypertensive agent through ACE inhibition using in silico methods. Methods: The study was conducted by analyzing the compound content of the ethanol extract of Avicennia marina stem using LC-HRMS. Biological activity was predicted using PASS Online, physicochemical properties were evaluated using Lipinski’s Rule of Five via SwissADME, toxicity was assessed with ProTox-II, and molecular docking was performed on the ACE target. Results: The study identified 49 metabolites, of which 38 were predicted to have antihypertensive activity based on PASS Online analysis. A total of 48 compounds met the parameters of Lipinski’s Rule of Five and 15 were predicted to be safe with a low likelihood of toxicity. Docking analysis revealed binding affinity values between metabolites and ACE inhibitors ranging from -4.785 to -10.019 kcal/mol. With the binding affinity of the native ligand at -11.185 kcal/mol and the standard reference inhibitor at -8.054 kcal/mol. The binding affinity of the native ligand was -11.185 kcal/mol, while that of the reference inhibitor was -8.054 kcal/mol. Amino acid residue analysis showed that 30 compounds from the ethanol extract of Avicennia marina shared common binding site residues with both the native ligand and the reference inhibitor. Among the identified compounds, verbascoside demonstrated the strongest binding affinity, with a value of -10.019 kcal/mol. Conclusion The ethanol extract of Avicennia marina stem exhibited potential antihypertensive activity. In silico analysis identified 30 compounds with ACE inhibitory activity, and 10 compounds met the criteria for physicochemical properties based on Lipinski’s Rule of Five, along with favorable toxicity predictions.