Table 1. Natural compounds activating cell survival system.
|
Compound
|
Dose |
Experimental disease model |
Specific target pathway |
Research outcomes and molecular changes |
Ref. |
|
|
Phenolic compounds |
||||||
|
Sulfuretin
|
20 μM |
SH-SY5Y cells and primary hippocampal neurons treated with Aβ25–35 |
PI3K/Akt and Nrf2/HO-1 Pathways |
↑Cell survival ↓ ROS, ↑HO-1 ↑PI3K/Akt ↑Nrf2 |
[48] |
|
|
Resveratrol |
20, 40 mg/kg |
SAMP8 mice (AD model) |
Nrf2/HO-1 signaling |
Attenuation of memory loss ↑SOD, GSH-Px, CAT, and HO-1 ↑Nrf2 ↓MDA, ↓ Erβ and Aβ ↑ChAT protein expression |
[50] |
|
|
10, 20, 40 μM |
PC12 cells treated with Aβ1-42 |
PI3K/Akt/Nrf2 pathway |
↑Cell survival ↑HO-1, Nrf2, PI3K, and p-Akt ↓MDA and ROS |
[49] |
||
|
Sitagliptin, quercetin and its combination |
100 mg/kg |
Aβ induced AD male Sprague-Dawley rats |
Nrf2/HO-1 pathway |
Attenuation of memory loss ↑SOD, CAT and GSH, ↓MDA, Aβ1-42 |
[54] |
|
|
Rutin |
200 mg/kg p.o. daily |
Acrylamide or γ-radiation-induced neurotoxicity in male albino SD rats |
PI3K/Akt/GSK-3β/Nrf-2 pathway |
↑p-PI3K, p-Akt, p-GSK-3β ↑NRF-2, ↓MDA ↓GST ↓IL-1b, IL-6 ↑IGF1, NGF |
[51] |
|
|
Hesperidin |
50 mg/kg b. w |
1-Methyl-4-phenyl-1,2,3, |
|
↑ IL-1β, TNF-α, IL- 6,4,10 |
[91] |
|
|
|
50 or 100 mg/kg per day) |
|
MDA and H2O2 level/ GSH/ T-AOC/ GSK-3β |
↓ MDA and H2O2 level |
[52] |
|
|
Oleuropein |
100 mg/kg |
|
↓Cerebral infarct volume ↓cleaved caspase-3 ↑Bcl-2 ↓Bax |
[53] |
||
|
Non-phenolic compounds |
||||||
|
Brassicaphenanthrene A
|
2.5–25 µM |
Glutamate-induced excitotoxicity in HT-22 neuronal cells
|
Nrf2/HO‑1, PI3K/Akt and JNK pathways |
↑HO-1, Nrf2 ↑GSH ↑Nrf2 nuclear translocation ↑pAkt |
[55] |
|
|
Acerogenin A |
30 uM |
Glutamate-induced neurotoxicity in HT22 cell line |
PI3K/Akt/Nrf2/HO-1 pathway |
↓ROS ↑HO-1 ↑Nrf2 ↑pAkt |
[56] |
|
ROS, Reactive oxygen species; HO-1, Heme oxygenase-1; P13K, Phosphatidylinositol 3-kinase; Akt, Protein kinase B; Nrf2, Nuclear factor erythroid 2-related factor 2; SOD, Superoxide dismutase; GSH-Px, Glutathione peroxidase; CAT, Catalase; MDA, Malondialdehyde; ERβ, Estrogen receptor β; ChAT, Choline acetyl transferase; p-GSK-3β, Phospho Glycogen synthase kinase 3 beta; GST, Glutathione-S-transferase; IL-1β, Interleukin-1β; IL-6, Interleukin-6; IGF1, Insulin growth factor-1; NGF, Nerve growth factor; TNF-α , Tumor necrosis factor α; COX-2, Cyclooxygenase-2; GFAP, Glial fibrillary acidic protein; iNOS, Inducible nitric oxide synthase; H2O2, Hydrogen peroxide; T-AOC, Total antioxidant capacity; Bcl-2, B-cell lymphoma 2; Bax, BCL2 Associated X.