In Silico exploration of β-Glucogallin from Malacca Fruit (Phyllanthus emblica) as a dual inhibitor of ACE and AT1R in Chronic Kidney Disease

Abstract

Chronic Kidney Disease (CKD) is one of the leading causes of death worldwide, with hypertension as its primary risk factor. Activation of the renin-angiotensin system (RAS) contributes to CKD complications, including hypertension and renal fibrosis. β-Glucogallin, a bioactive compound isolated from Malacca fruit (Phyllanthus emblica), exhibits therapeutic potential in RAS modulation. This study aims to identify and evaluate the potential of β-Glucogallin as an angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) inhibitor through an in silico approach, thereby providing new insights for CKD treatment. The methods used include ligand and protein preparation, bioavailability and toxicity prediction, molecular docking, and molecular dynamics simulation. The result showed β-Glucogallin exhibits strong binding affinity and stable interactions with key residues of ACE (Gln281, His353, His383, and Tyr523), and AT1R (Trp84 and Lys199), with binding affinity values of -8,0 Kcal/mol for ACE and -7,4 Kcal/mol for AT1R. Molecular dynamics simulations demonstrated good stability of the ligand-protein complex, with RSMD and RMSF values below 3Å, indicating stable interactions during simulations and suggesting its potential as an effective inhibitor. Despite slight deviations, β-Glucogallin meets Lipinski criteria as a viable drug candidate for CKD treatment through RAS inhibition. The in silico approach facilitates the rapid identification of active compounds. These findings confirms that β-Glucogallin warrants further investigation as a drug candidate.