Table 8.
Other phytochemicals exerting neuroprotective activities in Alzheimer’s disease models.
| Phytochemical tested | Plant | Concentration/Dose tested | Disease model | NRF2-related mechanism | Other observed AD-related effects | Reference |
|---|---|---|---|---|---|---|
| Bacopa monnieri extract | Bacopa monnieri | • 10 to 100 μg/ml | • Neuro-2a tau-stressed cells | • Upregulation of NRF2 | • Reduction of GSK-3β phosphorylation | (138) |
| Dimethyl fumarate | Fumaria officinalis | • 100 mg/kg (i.g.) | • MEFs from wild type or Keap1-deficient mice | • Disruption of Keap1/NRF2 axis by inhibition of GSK-3β | • Modulation of tau phosphorylation | (75) |
| Melatonin |
Scutellaria biacalensis, Tanacetum parthenium, Hypericum perforatum, Common food |
• 0.1 to 100 μM | • N9 microglia • Neuro-2a cells |
• Cellular increase and nuclear translocation of NRF2 | • Downregulation of GSK-3β | (140) |
| Oxyphylla A | Alpinia oxyphylla | • 12.5-100 μM | • N2a/APP cells • SAMP8 mice |
• NRF2 activation through Akt-GSK-3β pathway | • Decrease of Keap1 • Decrease of APP and Aβ levels |
(141) |
| EGb761 | Ginkgo biloba | • 25, 50, 100 and 250 μg/ml | • SH-SY5Y cells | • Upregulation of NRF2 | • Upregulation of HO-1, p-Akt and Bcl-2 • Decrease of caspase-3 and BAX |
(142) |
| Forsythoside A | Forsythia suspensa (Thunb.) Vahl. | • 40 and 80 μM • 30 mg/kg |
• Aβ1-42-treated N2a cells • Erastin-treated HT22 cells • LPS-induced BV-2 cells • APP/PS1 AD mouse model |
• Activation of NRF2/GPx4 axis | • Decreased lipid peroxidation, iron deposition, IL-6, NO, IL-1, NF-kB signaling, ferroptosis, neuroinflammation • Increased mitochondrial activity, dopaminergic signaling, anti-inflammatory cytokines • Improvement of memory and cognitive deficits • Reduced Aβ deposition and p-tau in the brain |
(143) |
| Curcumin analogues (FE, CB) | Curcuma longa | • 0.1, 1, 5, 10 and 20 μM | • Aβ25-35-treated PC12 cells | • Upregulation of NRF2/HO-1 • Decrease of Keap1 |
• Upregulation of SOD, CAT and Bcl-2 • Decrease of BAX and Cytochrome c |
(144) |
| Benincasa hispida fruits extract | Benincasa hispida | • 250 and 500 mg/kg/day | • Young Male Sprague-Dawley AD rats | • Upregulation of Keap1, NRF2, HO-1 genes | • Alleviation of ACh, dopamine and serotonin levels • Upregulation of antioxidant enzymes i.e. SOD, CAT, GSH • Decrease of MDA, TNF-a and IL-1β |
(146) |
| 3H-1,2-dithiole-3-thione | Cruciferous vegetables | • 10 and 20 mg/kg | • Tg2576 AD mouse model | • Upregulation of SIRT1/NRF2/HO-1 | • Decrease of insoluble Aβ level | (147) |
| Sulphoraphane | Cruciferous vegetables | • 1.25 and 2.5 μM | • N2a/Wt cells • N2a/APPswe cells |
• Upregulation of NRF2 • Nuclear translocation of NRF2 by decreasing DNA demethylation levels of its promoter |
• Decrease of Aβ1-40, Aβ1-42 and intracellular Aβ1-42, ROS, MDA • Increase of SOD activity • Decrease of IL-1β, IL-6, NF-kB, p65, COX-2, iNOS |
(148) |
| Osthole | Medicinal plants (Cnidium monnieri, Angelica pubescens etc.) | • 20 and 40 μM • 15 and 30 mg/kg |
• L-Glu-induced HT22 cells • APP/PS1 transgenic mice |
• Upregulation of NRF2 and its downstream proteins | • Upregulation of SOD and HO-1 • Inhibition of caspase-3, -8 and -9 • Reduction of ROS |
(149) |
| Plumbagin | Genus Plumbago | • 0.5 and 1 mg/kg/day | • STZ-induced AD mice | • Upregulation of NRF2/ARE pathway | • Astrogliosis suppression • Inhibition of BACE1 |
(150) |
| Hibiscus sabdariffa L. extract, hydroxycitric acid | Hibiscus sabdariffa | • 0.25, 0.5 and 1 mg/ml | • C. elegans | • Increase of the nuclear localization of SKN-1/NRF2 and DAF-16/FOXO | • Life extension of C. elegans | (151) |
NRF2, nuclear factor erythroid 2-related factor 2; GSK-3β, glycogen synthase kinase 3 beta; i.g., intragastrically; MEFs, mouse embryonic fibroblasts; Keap1, Kelch like ECH associated protein 1; APP, amyloid precursor protein; Akt, protein kinase B; Aβ, β-amyloid; HO-1, heme oxygenase-1; Bcl-2, B-cell lymphoma 2; BAX, bcl-2 associated X protein; LPS, lipopolysaccharide; APP/PS1, amyloid precursor protein/presenilin 1; AD, Alzheimer’s disease; GPx4, glutathione peroxidase 4; IL-6, interleukin-6; NO, nitric oxide; IL-1, interleukin-1; NF-kB, nuclear factor kappa B; p-tau, phosphorylated protein tau; SOD, superoxide dismutase; CAT, catalase; ACh, acetylcholine; GSH, glutathione; MDA, malondialdehyde; TNF-a, tumor necrosis factor a; SIRT1, sirtuin 1; ROS, reactive oxygen species; COX-2, cyclooxygenase 2; iNOS, inducible nitric oxide synthase; L-Glu, L-glutamate; STZ, streptozotocin; ARE, antioxidant response element; BACE1, beta-secretase 1; SKN-1, protein skinhead-1; FOXO, forkhead box protein O; C. elegans, Caenorhabditis elegans.