Standardized Hydroxytyrosol-Enriched Olive Pomace Juice Modulates Metabolic and Neurotrophic Signaling Pathways to Attenuate Neuroinflammation and Protect Neuronal Cells

TL;DR

This study shows that olive pomace juice, rich in hydroxytyrosol, protects neurons and reduces inflammation, offering potential for neurodegenerative disease treatments.

Contribution

The study identifies hydroxytyrosol as the key compound in olive pomace juice responsible for neuroprotection and anti-inflammatory effects.

Findings

OPJ reduced H2O2-induced neuronal cell death and inhibited amyloid fibril formation.

Hydroxytyrosol showed greater neuroprotective and anti-inflammatory effects than tyrosol.

OPJ modulated antioxidant, anti-apoptotic, and neurotrophic pathways via Nrf2, AMPKα–SIRT1–PGC1α, and CREB–BDNF–TrkB signaling.

Abstract

Olive pomace (OP), a by-product of olive oil production, is a sustainable resource rich in bioactive compounds with potential applications in cosmetics and pharmaceuticals. This study investigates the protective effects of olive pomace juice (OPJ) against H2O2-induced neuronal damage and LPS-induced inflammatory responses in HT22 and BV2 cells, respectively. OPJ suppressed H2O2-induced cell death and exerted anti-apoptotic effects by reducing the BAX/BCL2 ratio and caspase-3 cleavage. OPJ also mitigated neurodegenerative hallmarks by decreasing amyloid fibrils formation and inhibiting β-secretase and acetylcholinesterase (AChE) activity. Mechanistically, OPJ enhanced antioxidant response by upregulating Nrf2 and its downstream molecule HO-1, along with increasing mRNA levels of antioxidant enzymes, including catalase, SOD1, and GPx. OPJ further activated AMPKα–SIRT1–PGC1α signaling and CREB–BDNF–TrkB signaling, suggesting modulation of key antioxidant, anti-apoptotic, and neurotrophic pathways. In BV2 cells, OPJ downregulated pro-inflammatory cytokines (IL-6 and IL-1β) and decreased iNOS and COX-2 expression through suppression of NF-κB and MAPK signaling pathways. HPLC analysis identified hydroxytyrosol (10.92%) as the major active compound in OPJ, which compared with tyrosol (2.18%), and hydroxytyrosol exhibited greater neuroprotective and anti-inflammatory effects than tyrosol. This study highlights the potential of OPJ and its major compound, hydroxytyrosol, as functional agents for mitigating neurodegeneration-related cellular response, supporting its application in the food and pharmaceutical industries.

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