Characterization of Phenolic Compounds in Almond Skin Extracts by UPLC-TripleTOF-MS/MS and Their Protective Effects Against Cyclopiazonic Acid-Induced Toxicity in SH-SY5Y Cells.

Almonds are widely cultivated in Mediterranean regions, and their processing generates by-products such as almond skins, which are often discarded or used in low-value applications, leading to economic and environmental concerns. These skins are rich in bioactive compounds like polyphenols and flavonoids, with putative protective effects against toxins. Fungi such as Aspergillus and Penicillium species can contaminate nuts and their by-products and produce neurotoxic metabolites, like cyclopiazonic acid (CPA). This study aimed to characterize the phenolic compounds in aqueous extracts of almond skin and evaluate their cytoprotective effects on the viability of human neuroblastoma cells (SH-SY5Y) under individual CPA exposure and simultaneous co-exposure with almond skin extract. The extracts were optimized for extraction conditions, and UPLC-Triple-TOF-MS/MS analysis identified epicatechin, quercetin and kaempferol as the predominant phenolic compounds. Also, cell viability results showed that CPA induced cytotoxic effects on SH-SY5Y cells in a concentration-dependent manner. However, cells exposed to almond skin extract, at various dilutions (from 1/4 to 1/16), significantly increased cell viability from 43% to 57% relative to the control. Moreover, when SH-SY5Y cells were simultaneously co-exposed to CPA (400-600 nmol/L) and almond skin extract (1/4 dilution), a partial attenuation of CPA-induced toxicity (from 9% at 400 nmol/L to 20% at 600 nmol/L) was observed when compared with CPA alone. These findings suggest cytoprotective potential of almond skin extract in an in vitro neuronal-like model which may be associated with their content of phenolic compounds, providing new insights into their action against the emerging mycotoxin CPA, which remains underexplored in food safety research.