Green Ultrasonic-Assisted Extraction of Bioactive Phenolic Constituents from Gastrodia elata: Process Optimization, Chemical Characterization, and In Vitro Antioxidant, Anti-Inflammatory, and Hepatoprotective Activities

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To promote the comprehensive utilization of Gastrodia elata (GE) resources, an efficient ultrasonic-assisted extraction (UAE) method was developed to enrich gastrodin (GAS) and phenolic constituents, which possess sedative, neuroprotective and hepatoprotective activities and exhibit promising application prospects for nutraceutical, functional food and pharmaceutical fields. Extraction parameters were optimized using a Box–Behnken design (three factors, three levels; R2 = 0.9745, adjusted R2 = 0.9417, lack-of-fit p = 0.5599). The optimized conditions were 65% ethanol, a liquid–solid ratio of 30 mL/g, and 60 min; the model-predicted GAS yield was 4.005 mg/g DW. UPLC-Q-TOF-MS/MS tentatively identified 32 constituents, and HPLC quantified six major compounds: parishin A (9.233 mg/g DW), parishin B (5.281 mg/g DW), GAS (4.215 mg/g DW), parishin E (3.950 mg/g DW), parishin C (1.233 mg/g DW), and p-hydroxybenzyl alcohol (0.871 mg/g DW). At 100–400 μg/mL, the extract significantly elevated SOD/GSH levels, reduced ALT/AST in a 3% ethanol-induced HepG2 hepatotoxicity model, and suppressed LPS-stimulated TNF-α/IL-6 while increasing IL-10 in RAW 264.7 macrophages (n = 3). It should be noted that anti-inflammatory assays in the present work were performed without dedicated positive reference compounds. Further investigations are required to validate bioactivities in vivo, test individual isolated constituents, and evaluate scalability together with formulation feasibility. This work provides a green, efficient strategy for the high-value utilization of GE bioactives.