GC-MS Profiling and In Silico Evaluation of Acalypha wilkesiana Leaf Phytocompounds for Antimicrobial, Antioxidant, and Anti-Inflammatory Activity in Oral Health

Abstract

In many local communities, the leaves of Acalypha wilkesiana (Euphorbiaceae) are chewed to manage toothache and other dental inflammations. Despite this widespread ethnomedicinal practice, the phytochemical basis and molecular mechanisms underlying these oral health benefits remain poorly understood. This study aimed to identify the bioactive phytoconstituents in the ethanolic leaf extract of A. wilkesiana using gas chromatography-mass spectrometry (GC-MS) and to evaluate their antimicrobial, antioxidant, and anti-inflammatory potential through molecular docking, drug-likeness, and toxicity prediction. Ethanol extract of A. wilkesiana leaf was analyzed by GC-MS, and the identified compounds were subjected to molecular docking against four target proteins: Streptococcus mutans glucosyltransferase B (PDB: 8FJC), Candida albicans exo-1,3-beta-glucanase, human glutathione peroxidase, and cyclooxygenase-2. Drug-likeness was assessed using Lipinski and Veber rules, and toxicity was predicted using ProTox-II. Sixty two compounds were identified with squalene (21.13%), oleic acid (17.62%), and 13-octadecenal, (Z)- (16.63%) as the most abundant. Molecular docking revealed that Aspidospermidin-17-ol, 1-acetyl-19,21-epoxy-15,16-dimethoxy- exhibited the highest binding affinities against 8FJC (-7.8 kcal/mol), 2HE3 (-6.9 kcal/mol), and 3NTG (-7.6 kcal/mol), while cyclotetradecane, 1,7,11-trimethyl-4-(1-methylethyl)- showed the strongest binding to 4M81 (-9.6 kcal/mol). Drug-likeness analysis indicated that epinephrine, aspidospermidin-17-ol, 1-acetyl-19,21-epoxy-15,16-dimethoxy-, 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione, and dibutyl phthalate complied with Lipinski's rules. Toxicity prediction showed that most compounds fell within Classes IV–VI (low to non-toxic). No hepatotoxicity or mutagenicity was predicted for any phytocompound. The ethanolic leaf extract of A. wilkesiana contains a diverse array of bioactive compounds demonstrating promising activity against bacterial, antioxidant, and inflammatory proteins. These findings provide a scientific basis for the local practice of chewing A. wilkesiana leaves for dental relief and support further investigation of its lead compounds for phytodentistry applications.