Multivariate analysis and ADME profiling of Rosmarinus officinalis L. leaf vs. stem extracts: Extraction method-driven bioactivity and pharmacokinetic implications

This study evaluated the bioactive potential of Rosmarinus officinalis L. extracts obtained separately from leaves and stems, comparing maceration (ME), Soxhlet (SE), and ultrasound-assisted extraction (UAE) techniques. Phytochemical profiling was performed using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (LC-ESI-MS/MS). Analyses quantified total phenols (TPC), flavonoids (TFC), antioxidant capacity (DPPH, FRAP, ABTS assays), and antimicrobial activity against Escherichia coli and Streptomyces scabies . Significant differences were observed between plant parts. SE of stems yielded the highest TPC (159.7 mg gallic acid equivalents/g). UAE most effectively recovered antioxidant diterpenes (e.g., carnosic acid, carnosol), producing the strongest antioxidant activity (DPPH IC 50 = 11.95-16.30 μg/mL). Notably, stem extracts exhibited superior antimicrobial activity compared to leaf extracts, with UAE extracts demonstrating the highest efficacy against S. scabies (35 mm inhibition zone at 100 mg/mL). In silico absorption, distribution, metabolism, and excretion (ADME) predictions linked the lipophilicity (WLogP 3.25-5.87) of these diterpenes to their antimicrobial potency. Multivariate analyses clustered extracts primarily by extraction method and secondarily by plant part. Overall, fractionating rosemary into stems and leaves is crucial, as stems provide enhanced antimicrobial activity. UAE of stems is optimal for topical applications, whereas SE and ME may be more suitable for oral delivery.