Influence of Extraction Method on the Bioactivity of Pistachio Extracts: Metabolic and Gene Expression Changes in Colorectal Cancer Cells

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Sustainable extraction methods represent a key strategy in green chemistry and nutraceutical development, aiming to replace conventional solvent-based techniques while maintaining extract quality and safety. This study compared pistachio ( Pistacia vera L.) extracts obtained by ultrasound-assisted extraction (UAE) and a traditional solvent-based protocol, focusing on compositional features and biological effects. Ex-tracts were characterized for their chemical profiles, and their impact on HCT-116 co-lon-derived cells was evaluated through viability assays and gene expression analysis. The UAE-derived extract, richer in carbohydrates, promoted higher cell proliferation after 72 h, whereas the classical extract upregulated HMOX-1, suggesting activation of antioxidant defense pathways. Moreover, UAE treatment downregulated GLUT2 ex-pression while increasing IL-6 and IL-10 transcripts, indicating a possible carbohy-drate-driven immunometabolic response. Overall, these findings highlight both the advantages and limitations of green extraction approaches: while environmentally sustainable and efficient, ultrasound-assisted protocols may modify extract composi-tion in ways that influence biological responses. Optimization of extraction parameters is therefore essential to ensure a balance between ecological sustainability, composi-tional integrity, and biological safety.

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