Chemical Profiling, Box-Behnken Optimisation, Antimicrobial Activity, and Molecular Docking Study of Z-Ligustilide...

Angelica glauca Edgew., a high-altitude Himalayan medicinal plant, is an important source of bioactive essential oil rich in phthalide derivatives. The present study investigated the influence of environmental conditions and extraction parameters on essential oil yield and chemical composition, with particular emphasis on Z-ligustilide. Essential oils obtained from roots collected across different altitudes revealed marked variations in yield and phytochemical profile, with plants growing at 3500-3800 m producing the highest concentration of Z-ligustilide (75.2%). The optimised essential oil exhibited broad-spectrum antimicrobial activity against both Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Candida species. Molecular docking studies further supported its therapeutic potential by demonstrating strong interactions with microbial target proteins, with binding affinities reaching approximately -6.9 kcal/mol. The predicted mechanisms of antimicrobial action include membrane disruption, interference with ATP production, and inhibition of biofilm formation, indicating a multi-target mode of action. Overall, these findings demonstrate that altitude-driven phytochemical variation combined with optimised extraction significantly enhances the quality and biological efficacy of A. glauca root oil, highlighting its potential as a natural antimicrobial agent for pharmaceutical and nutraceutical applications.