Extraction Methods Shape the Phenolic Composition and Bioactivities of Defatted Moroccan Pistacia lentiscus L. Resin

Mastic gum from Pistacia lentiscus L. has long been valued in Mediterranean medicine and food preservation, yet its bioactive potential remains underexplored in specific geographic contexts. In Morocco, the resin-locally known as Meska Horra-is abundant but insufficiently characterized. This study compared three extraction methods-cold maceration (CM), Soxhlet extraction (SE), and ultrasound-assisted extraction (UAE)-using sequential acetone and 70% ethanol to recover complementary phenolic compounds from defatted resin. Targeted UHPLC-ESI-MS/MS profiling identified and quantified 30 phenolics, mainly flavonoids and phenolic acids, providing the first systematic dataset for Moroccan mastic gum. UAE-EtOH extract displayed the strongest antioxidant activity (DPPH IC₅₀ = 0.029 mg/mL; ABTS•⁺ IC₅₀ = 0.026 mg/mL). SE-acetone and SE-EtOH extracts showed potent antifungal activity, particularly against Geotrichum candidum, Rhodotorula glutinis, and Aspergillus niger (MBC = 1.7%). The SE-acetone extract exhibited cytotoxicity toward MIA PaCa-2 pancreatic cancer cells (IC₅₀ = 19 µg/mL). These findings demonstrate that extraction method and solvent choice strongly influence phenolic recovery and associated bioactivities, supporting the valorization of Moroccan mastic gum as a promising source for nutraceutical and pharmaceutical applications.