Table 2.
Summary of key neurobeneficial effects of Olea europaea L. polyphenols.
| Polyphenol | Study Type | Model/Cell Type | Effects * | Reference |
|---|---|---|---|---|
| Hydroxytyrosol (HT) | In vitro | BV2 microglia and primary microglia cells | AI: Dose-dependent decrease of pro-inflammatory mediators (modulation of M1/M2 polarization), TLR4 (NF-κB p65 and ERK signaling) | [75] |
| NP: Complete inhibition of α-syn aggregation with HT-acetate | [215] | |||
| In vivo | Mouse | AI: Dose-dependent decrease of pro-inflammatory mediators, microglia/astrocyte activation | [75] | |
| C. elegans | NP: 76.2% inhibition of α-syn aggregation with HT-acetate | [215] | ||
| Oleuropein (OL) | In vitro | Molecular dynamics trajectory analysis | NP: Stabilizes α-syn monomer and nontoxic aggregates | [113] |
| (LPS)-treated monocyte/macrophages (THP-1) and endothelial cells (HUVECs), senescent HUVECs and Poly(I:C)-treated small airway epithelial cells (hSAECs) | AI: Decreased pro-inflammatory mediators (IL-1β, TNF-α, IL-8, ICAM, VCAM) and release of IL-6. In hSAECs, modulates the expression of SOD2, NF-kB, ACE2 and TMPRSS2 | [127] | ||
| CD4+ T cells from PBMCs of healthy controls and rheumatoid arthritis patients | AI: Dose-dependent increase in frequency of CD4+ CD25+ FoxP3 Tregs, IL-10 and TGF-β production | [199] | ||
| In vivo | 3 mo 5XFAD AD model | AI: Inhibition of NF-κB, NLRP3 inflammasomes and RAGE/HMGB1 pathways NP: Reduction of total Aβ brain levels and enhanced BBB integrity and function |
[200] | |
| C. elegans | AO: Decreased oxidative stress involving DAF-16/FOXO and SKN-1/NRF2, and HSP-16.2 NP: Decreasesd Aβ and tau aggregation |
[216] | ||
| Rotenone PD model | NP: Increased CREB and phosphorylation of Akt and GSK-3β; reduction of mitochondrial dysfunction by activation of enzyme complexes and downregulation of the proapoptotic markers | [222] | ||
| Clinical | Probable mild AD patients | NP: Neurocognitive parameters stabilized or improved | [136] | |
| Oleocanthal (OC) | In vitro | Adipocytes | AI: Decreased TNF-α induced IL-1β, COX-2 Decreased TNF-α induced MCP-1, CXCL-10, M-CSF Decreased TNF-α induced miR-155-5p, miR-34a-5p and let-7c-5p Increased PPARγ Decreased TNF-α induced NF-κB activation AO: Decreased TNF-α induced NADPH oxidase, SOD, GPX |
[206] |
| Murine peritoneal macrophages | AI: Decreased LPS-induced MAPK pathway, inflammasome cascade signaling pathway, IL-1β, IL-6, IL-17, INF-γ, and TNF-α AO: Decreased LPS-induced ROS production |
[213] | ||
| AO: Demonstrated ROS scavenger capacity against HOCl and O2●− | [133] | |||
| In vivo | 5XFAD AD model (females) | AI: COX inhibition, suppressed C3AR1 activity (via STAT3) AO: Decreased Aβ plaques and tau phosphorylation |
[66] | |
| 5XFAD AD model | AI: Decrease NF-κB pathway and NLRP3, OC only decreased RAGE/HMBG1 pathway NP: Decreased Aβ levels |
[66] | ||
| TgSwDI AD model, (6 months) | AI: Inhibition of NACHT, LRR, and NLRP3 NP: Restored BBB function, reduced Aβ pathology induced autophagy through activation of AMPK/ ULK1 pathway |
[132] | ||
| Clinical | Obese and prediabetic individuals | AI: Decreased IFN-γ NP: Increased total antioxidant status, decreased lipid and organic peroxides |
[154] |
* Anti-inflammatory (AI), Antioxidant (AO) and Neuroprotective (NP).