Table 3.
Neuroprotective effects of HTyr.
| Neuroprotection Model | System | Action | Reference |
|---|---|---|---|
| In vitro | Mouse brain dissociated cells | HTyr enhances ATP production; ligstroside enhances mitochondrial respiration | [245] |
| Cell lines/microglia | BV2 microglia cells LPS-treated | HTyr reduces pro-inflammatory CD86 and p-NF-kB p65, increased anti-inflammatory CD206 | [246] |
| BV2 cells α-synuclein-treated | HTyr reduces NADP oxidase as well as NLRP3 levels (the latter LPS-induced) | [247] | |
| PC12 cells H2O2-treated | HTyr activates Keap1-Nrf2, upregulating its cytoprotective targets: GCLC, HO-1, NQO1, TXNRD1 | [144] | |
| PC12 cells salsolinol-treated | HTyr increases SOD, catalase (CAT), glutathione reductase (GR), and peroxidase (GPX) | [249] | |
| Diabetic rat brain slices | HTyr reduces lipid peroxidation, nitric oxide, and peroxynitrite concentration | [250] | |
| Ex vivo | Normal rat brain slices | HTyr reduces cell death, measured by LDH efflux to the incubation medium | [251] |
| Hypoxia-reoxygenation | Normal rat brain slices | HTyr (in vitro/oral) reduces inflammatory molecules PGE2 and IL-1β reoxygenation-induced | [252] |
| Normal rat brain slices | HTyr synergizes with dihydroxyphenylglycol and oleocanthal in cytoprotective/antioxidant effects | [253] | |
| Normal rat brain slices | HTyr-ethyl ether (with 2 OH groups) was more effective as antioxidant than with 1 OH or no OH | [254] | |
| In vivo | Aged and young mice | HTyr enhances survival of hippocampal neurons, integrated in circuits, as they are c-fos-positive | [47] |
| Mice/Rats | Mice, depressed by CUMS | HTyr decreases oxidative stress by increasing SOD activity, reduces ROS and microglia activation | [226] |
| Subarachnoid hemorrage | HTyr (100 mg/Kg/day, 6 weeks) reduces NF-kB levels and restored SOD, GPX, and CAT | [255] | |
| In vivo | Diabetic (STZ-treated) rats | HTyr (5 mg/Kg/day, 2 months) reduces the decrease of retinal ganglion cells; neuroprotective effect | [256] |
| Retinopathy | Retinal cell line ARPE-19 | HTyr protects ARPE-19 cells from acrolein-induced oxidative damage and mitochondrial dysfunction | [257] |
| AMD in humans | HTyr (plus resveratrol/carotenoids) reduces inflammation in age-related macular degeneration (AMD) | [258] | |
| Diabetes model M. shawi | OLE protects retinal cells in culture against the toxic effect of glucose | [188] | |
| HTyr derivatives | SH-SY5Y cells H2O2-treated | Nitro-HTyr reduced ROS and chelated several metal cations | [259] |
| Anti-oxidation assays | Alkyl nitrohydroxytyrosyl ether derivatives of HTyr: greater antioxidant activity with 2–4 carbon atom | [260] | |
| Intrastriatal infusion of MPP+ | HTyr, HTyr acetate, or nitroHTyr reduce dopaminergic stress and increases GSH/GSSG ratio | [149] | |
| Brain slices | Alkyl-HTyr ethers: more antioxidant than HTyr against lipid peroxidation hypoxia-reoxygenation | [261] | |
| Liposome biomembranes | HTyr ester moieties linked by a lipophilic spacer protect liposome from induced oxidation | [262] |
Abbreviations: Adenosine triphosphate (ATP), nuclear factor kappa B (NF-kB), NLR family pyrin domain containing 3 (NLRP3), glutamate–cysteine ligase (GCLC), heme oxygenase 1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1), thioredoxin reductase (TXNRD1), lactate dehydrogenase (LDH), prostaglandin E2 (PGE2), interleukin 1β (IL-1β), superoxide dismutase (SOD), glutathione/glutathione disulfide ratio (GSH/GSSG ratio), chronic unpredictable mild stress (CUMS), streptozotocin (STZ), Meriones shawi (M. shawi).