Hedyotis diffusa Aerial Parts: Essential Oil Composition, Biological Activity, and In Silico Approach.

Hedyotis diffusa, a widely used medicinal herb in Asia, has underexplored essential oils. This study aimed to analyze the chemical composition and biological activities of essential oils from H. diffusa aerial parts. Essential oils from stem barks and leaves were examined via gas chromatography-flame ionization detection/mass spectrometry. Biological activities were assessed using cytotoxicity (MCF7, SK-LU-1, and HepG2), antimicrobial (Bacillus subtilis), nitric oxide (NO) inhibition, antioxidant, and antidiabetic assays. Molecular docking targeted human epidermal growth factor receptor 2 (HER2) and B-cell lymphoma 2 (BCL2) proteins, with Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling predicting pharmacokinetics. Major compounds of the essential oils included hexadecanoic acid (22.7%-24.5%), pentadecanal (15.4%-16.0%), and (5E,9Z)-farnesyl acetone (13.0%), alongside cyclohexyl anthranilate (6.2%) and cis-phytol (4.8%-5.5%). The stem bark essential oil showed strong cytotoxicity (inhibitory concentration of 50% [IC50]: 10.86-14.92 µg/mL) and antimicrobial activity (minimum inhibitory concentration: 32 µg/mL against B. subtilis), while both essential oils inhibited NO production (IC50: 36.81-40.58 µg/mL) with moderate antioxidative and antidiabetic effects. Docking revealed the affinities of cyclohexyl anthranilate for HER2 (ΔG: -8.423 kcal/mol) and (5E,9Z)-farnesyl acetone for BCL2 (ΔG: -5.81 kcal/mol), with favorable ADMET profiles. Essential oils from Vietnamese H. diffusa aerial parts exhibit promising bioactivity and pharmacokinetics, supporting traditional use and warranting further medicinal research.