A Novel Green Infrared-ultrasound Hydrodistillation Method Enhances Yield and Bioactivity of Salvia sclarea Essential Oil: Mechanistic Insights into Its Anti-inflammatory and Gastroprotective Effects

Objective: The primary aim of this study was to develop and optimize a novel infrared-ultrasound hydrodistillation method coupled with in-line gas chromatography–mass spectrometry (IR–US–HD–GC/MS) for the eco-efficient extraction of Salvia sclarea essential oil (EO). The secondary aim was to evaluate the antioxidant, anti-inflammatory, and gastroprotective effects of the optimized EO in validated in vivo models. Materials and Methods: A novel IR–US–HD–GC/MS apparatus was assembled and compared with microwave-assisted hydrodistillation (MW-HD) and conventional hydrodistillation (HD). The EOs were chemically characterized, and the most promising extract was tested in two gastric ulcer models (HCl/ethanol and hypothermia). Anti-inflammatory mechanisms were investigated through cytokine assays, NF-κB, cyclooxygenase-2 (COX-2), and antioxidant markers. Results: The novel IR–US–HD–GC/MS method significantly improved EO yield (5.8 mL/kg vs. 3.0 mL/kg with HD), reduced extraction time (15 min vs. 5 h), and lowered energy consumption by 90%. The optimized EO (200 mg/kg) produced strong gastroprotection, reducing ulcer area by 74.9% in the HCl/ethanol model and 49.6% in the hypothermia model, comparable to ranitidine. Biochemically, treatment reduced tumor necrosis factor-alpha (72.8%), interleukin-6 (IL-6) (71.2%), NF-κB (IC 50 = 88.7 mg/kg), and COX-2 (IC 50 = 112.2 mg/kg), while increasing IL-10 (1.3-fold) and restoring antioxidant balance (MDA decreased by 46%; GSH increased by ca. 2-fold; CAT increased by 1.25-fold). Conclusions: The IR–US–HD–GC/MS method is a green, time- and energy-efficient technology that enhances both yield and bioactivity of S. sclarea EO. The optimized oil demonstrates significant multi-targeted antioxidant, anti-inflammatory, and gastroprotective effects, supporting its potential as a safe phytotherapeutic candidate for inflammatory gastric disorders.