Table I.
Biological effects of astaxanthin in Alzheimer's Disease, Parkinson Disease, Cerebral Ischemia/Reperfusion, Subarachnoid Hemorrhage and Amyotrophic lateral sclerosis.
| Author, year | Target, cell line | Effect | Concentration | Intervention | Duration | Outcome | Disease | (Refs.) |
|---|---|---|---|---|---|---|---|---|
| Ito, 2019 | Human | Neuroprotective | 3 mg AST + 5 mg sesamin, oral | Post-treatment | 12 weeks | Psychomotor speed,↑ processing speed | MCI | (71) |
| Sekikawa, 2020 | Human | Neuroprotective | 9 mg AST + 50 mg tocotrienol, oral | Post-treatment | 12 weeks | Composite memory↑ and verbal memory | Cognition | (72) |
| Taksima, 2019 | Male Wistar rats, | Anti-oxidant | 10 mg/kg/day, oral | Post-treatment | 30 days | Learning and memory↑ ability, glutathione peroxidase, neuronal survival; MDA, protein carbonyl | AD | (73) |
| Kim, 2020 | BV-2 microglial cells | Anti-inflammatory | 1-10 µg/ml | Pre-treatment | 4 h | IL-1β, TNF-α,↑ IL-6, pJNK activation, neuronal cell death; IL-10 and ↓ arginase-1, Akt phosphorylation | AD | (77) |
| Kim, 2010 | BV-2 microglial cells | Anti-inflammatory | 25 µM | Pre-treatment | 24 h | IL-6, p-IKKα,↓ | AD | (78) |
| p-IκBα, p-NF-κBp65 | AD | (79) | ||||||
| Wen, 2015 | Hippocampal HT22 cells anti-oxidant, | Anti-apoptosis | 1.25-5 µM | Pre-treatment | 2 h | cell viability, Bcl-2, HO-1, Nrf2, p-Akt,p-GSK-3β (Ser9) caspase-3/8/9 activity,↓ PARP, AIF, ROS, Bax, Cyt-c | ||
| Ye, 2013 | PC12 cells | Anti-oxidant | 10 µmol/l | Pre-treatment | 2 h | PC12 cell viability;↑ activated transcription factor, NMDA receptor↓ subunit 1 protein and mRNA | PD | (32) |
| Ye, 2012 | PC12 cells | Anti-oxidant | 10 µM | Pre-treatment | 2 h | ROS, NOX2↑ HO-1, Nrf2↓ | PD | (84) |
| Brasil, 2021 | Human neuroblastoma SH-SY5Y cells | Anti-oxidant | 20 µM | Pre-treatment | 24 h | H2O2-induced cytotoxicity↓ cytochrome c, caspase-9 and caspase-3, IL-1β and TNF-α; HO-1, Nrf2 ↑ | PD | (85) |
| Lee, 2011 | Human neuroblastoma SH-SY5Y cells, C57BL/6 mice | Anti-oxidant | 50 µM 10, 30 mg/kg/day/(animal model) | Pre-treatment | 24 h (cell), 28 days (animal model) | ROS, cytotoxicity,↓ a-synuclein Bax, caspase-3, argyrophilic neurons; Bcl-2, SOD,↑ catalase, tyrosine hydroxylase neurons | PD | (86) |
| Xue, 2017 | Male mice | ICR anti-oxidant | 10 mg/kg/day, intragastric | Post-treatment | 28 days | Learning and memory↑ ability, GSH, SOD, Bcl-2; Cyt c, Bax↓ | IR | (93) |
| Pan, 2017 | Male (Sprague Dawley) rat | SD anti-oxidant | 5 mg/kg, 10 mg/kg, intragastrical | Pre-treatment | 7 days | Nrf2, HO-1, NQO1,↑ Bcl-2, GFAP, MAP-2, BDNF, GAP-43; Infarction volume, Bax↓ | IR | (94) |
| Lee, 2010 | Human SY5Y neuroblastoma cells male Wistar rats | SH-anti-oxidant | 10, 25, 50, 100 µM 30 mg/kg, intra-peritoneally (animal model) | Pre-treatment | 90 min (cells), 0 and 90 min of cerebral reperfusion (animal model) | Neuronal cell↑ density, HO-1; NO, iNOS↓ | IR | (95) |
| Lu, 2010 | Male Sprague-Dawley rats | Anti-oxidant | 50, 80 mg/kg, oral | Pre-treatment | 5 and 1 h before ischemia | Infarct volume↓ cell viability↑ | IR | (96) |
| Yang, 2021 | SD rats | Anti-oxidant anti-inflammatory anti-apoptosis | 100 mg/kg, gavage | Pre-treatment | 3 days | Brain edema,↓ cerebral infarct area, TNF-α; IL-1β, IL-6, MDA,↑ Bax Nrf-2, HO-1, Bcl-2, CAT, SOD, GPX | IR | (97) |
| Wu, 2014 | Male SD rats | Anti-oxidant | 0.1 mM, left ventricle injection | Post-treatment | 24 h after SAH | Brain edema,↓ BBB disruption; BBB disruption; neurological scores, Nrf2, HO-1, NQO1, ↑ GST-α1 | SAH | (34) |
| Zhang, 2014 | Male SD rats, male New Zealand rabbits | Anti-oxidant | 0.01, 0.1 mmol/l intracerebroven-tricular injection 25, 75 mg/kg oral | Post-treatment | 30 min after SAH, 3 h after SAH | Brain edema, caspase-3,↓ MDA; BBB permeability,↑ GSH, SOD | SAH | (103) |
| Zhang, 2019 | Male SD rats, C57BL/6 mice, TLR4 gene KO mice | Anti-inflammatory | 01, 0.1 and 0.2 mM 20ml, left lateral ventricle injection (rat); 2.0 ml, right lateral ventricle injection (mice) | Post-treatment | 30 min, 4 h, or 8 h after SAH (rats), 30 min after SAH (mice) | IL-1b,TNF-a,↓ ICAM-1a, CD68 (+) microglia, NF-кB p65, p-IκB, Toll-like receptor 4 activation; Cell viability↑ | SAH | (102) |
| Wang, 2019 | Male SD rats | Anti-apoptosis | 75 mg/kg, gavage | Post-treatment | 3 h after SAH | Mitochondrial↑ membrane potential, synaptic protein, nerve growth and neuronal differentiation factors; Bax/Bcl-2 ratio,↓ Cyt c, caspase-3 | SAH | (104) |
| Isonaka, 2011 | Wistar rats | Antioxidant | 100 nM | Pretreatment | 24 h pretreatment + 72 h treatment period | Neurite lengths↑ | ALS | (109) |
Up arrows denote enhancement action and down arrows indicate inhibitory action. AST, astaxanthin; MCI, mild cognitive impairment; MDA, malondialdehyde; IL-1β, interleukin-1 β; TNF-α, tumor necrosis factor α; IL-6, interleukin-6; JNK, c-Jun N-terminal kinase; AD, Alzheimer's disease; p-IKKα, p-IκB kinase α; Bcl-2, B-cell lymphoma-2; HO-1, heme oxygenase-1; Nrf2, nuclear factor erythroid 2-related factor 2; Akt, Akt, protein kinase B; GSK-3β, glycogen synthase kinase 3β; PARP, poly (ADP-ribose) polymerase; AIF, apoptosis inducing factor; ROS, reactive oxygen species; Bax, BCL2-Associated X; Cyt-c, cytochrome c; NMDA, N-methyl-D-aspartate; PD, Parkinson's disease; NOX2, nitrogen oxide 2; SOD, superoxide dismutase; GSH, glutathione; IR, ischemic reperfusion; NQO1, NAD(P)H quinone oxidoreductase-1; GFAP, glial fibrillary acidic protein;MAP-2, microtubule-associated protein-2; BDNF, brain-derived neurotrophic factor; GAP-43, growth-associated protein 43; NO, nitric oxide; iNOS, inducible nitric oxide; MDA, malondialdehyde; CAT, catalase; GPX, Glutathione peroxidase; BBB, blood-brain barrier; GST-α1, glutathione-s-transferase-α1;SAH, subarachnoid hemorrhage; ICAM-1a, intercellular cell adhesion molecule-1 a; ALS, amyotrophic lateral sclerosis.