The development of polyphenol neuroprotective nutraceuticals useful for functional foods could be a valuable strategy for counteracting oxidative stress relative diseases as Alzheimer's Disease (AD). Oxidative stress is one of the AD earliest event and seems to play a central role in Aβ generation, neuroinflammation, and neuronal apoptosis. In order to counteract AD neurodegeneration, the inhibition of the vicious cycle of Aβ generation and oxidation is an attractive therapeutic strategy, and antiamyloidogenic and antioxidant plant drugs could represent an alternative and valid approach. In this context, an alcoholic extract (Pl-M) from deterpenated Pistacia lentiscus L. leaves was investigated for its phenol composition through LC-ESI-MS/MS analysis. Besides the identified metabolites, ten compounds were reported for the first time as constituents of Pistacia lentiscus leaves. Through DPPH, ABTS, and ORAC methods, the antioxidant potential of the extract was initially investigated. In order to evaluate the preparation of a safe and no toxic extract, MTT, SRB, and LDH assays toward SH-5YSY, and SK-N-BE(2)-C human neuronal cell lines, as well as on C6 mouse glial cell line, were performed. Evaluating the protective effects from oxidant injury in SK-N-BE(2)-C cells cotreated with the plant complex and H2O2, or Aβ(25-35) fragment, it was observed that Pl-M extract exerted a significant cytoprotective response in both the oxidized cell systems. In particular, Pl-M extract was able to reduce by nearly 50% the Aβ(25-35) induced toxicity at 25.0 μg/mL dose level, whereas it counteracted almost completely the cytotoxic action at 100.0 μg/mL. Data obtained allow us to hypothesize the use of Pistacia lentiscus leaves, a broadly available and renewable source, as an alternative strategy for the enrichment of food matrices with polyphenol bioactives. The present study put the basis for bioavailability and preclinical studies, able to define Pl-M extract safety and efficacy.
Keywords: LC-MS/MS metabolic fingerprinting; Pistacia lentiscus; antioxidant activity; neuroprotection; polyphenols.