Table 1 Treatment-related information of nobiletin
From: A review on recent advances on nobiletin in central and peripheral nervous system diseases
Dose and route of administration | Time | Model | Effects | References |
|---|---|---|---|---|
10, 50 or 100 µM | / | Cell-derived AD model | BACE1 inhibitory | [76] |
10 – 50 mg/kg (i.p.) | 7 d | AD model mice | Soluble Aβ1–40↓ learning and memory impairment ↓ | [40] |
0, 10, 50, 30 or 100 µM | 72 h | Cell-derived AD model (SK-N-SH cells) | Neprilysin activity ↑ | [10] |
3, 10 or 30 µM | 24 h | Cell-derived AD or normal neurons model | Neprilysin mRNA ↑ Aβ1–42 ↓ | [27] |
10 mg/kg (i.p.) | 4 m | AD model mice | Guanidine-soluble Aβ1–40 and Aβ1–42 ↓ | [45] |
1, 10, 25 or 50 µM | 1 h | Cell-derived AD or normal neurons model | Oxidative stress ↓ Interleukin-1 ↓ Tumour necrosis factor-α↓ Nitric oxide (NO)↓ Prostaglandin E2↓ Cyclooxygenase-2↓ c-Jun N-terminal kinase and p38 ↓ | [75] |
25, 50 or 75 mg/kg (p.o.) | 90 d | AD model mice | Apoptosis↓ IL-1β↓, TNF-α↓, and IL-18 levels ↓ HMGB-1↓, NLRP3↓, ASC↓ Cleaved Caspase-1↓, GSDMD-N ↓ | [8] |
30 mg/kg (p.o.) | 4 w | Aβ 1–42 injection mice model | AchE activity↑ Bax and cleaved caspase-3 ↓ Bcl-2 and Bcl-2/Bax ↑ | [30] |
50 mg/kg | 11 d | AD model mice | ChAT ↑ | [23] |
30 or 100 μM | 18 h | PC12D cells and hippocampal neurons | ChAT ↑, AchE ↑ Cholinergic neurodegeneration ↓ | [41] |
30 μM | 5 h | PC12D cells | CRE-mediated transcriptional Activity ↑ ERK phosphorylation level ↑ | [11] |
25 mg/kg | 7 d | AD Model mice | CRE-mediated transcriptional activity ↑ | [24] |
10 μM | / | PC12 cells | CRE-dependent transcriptional activity ↑ Erk phosphorylation ↑ | [58] |
10 or 50 mg/kg | 7 d | AD Model mice | CREB phosphorylation ↑ Learning ability ↑ | [38] |
100 μM | 8 h | PC12D cells | Neurite outgrowth ↑ Improve impaired memory ↑ CRE-dependent transcription ↑ | [39] |
10 or 50 mg/kg (i.p.) | 7 d | AD model mice | PKA/ERK/CREB signalling ↑ learning impairment ↓ | [2] |
100 μM | 15 min | PC12D cells | protein kinase A phosphorylation ↑ GluR1 receptor phosphorylation ↑ | [37] |
10 or 25 mg/kg (i.p.) | 3 d | AD model mice | phosphorylated ‑Akt ↑ CREB ↑, BDNF ↑ Bax ↓ | [5] |
25 or 50 mg/kg (i.p.) | 7 d | Stroke model mice | Calcium/calmodulin-dependent protein kinase II ↑ Microtubule-associated protein 2 ↑ Glutamate receptor 1 ↑ | [67] |
1 μM | 48 h | Cell hypoxia model | Astrocytes activation↓ Nrf2 nuclear translocation ↑ HO-1 expression ↑ GFAP ↓ ROS and MDA ↓ Mitochondrial dysfunction ↓ | [60] |
10 or 25 mg/kg(i.p.) | 3 d | Stroke model rat | Brain oedema ↓ Infarct volume ↓ p-Akt↑, CREB↑, BDNF↑, Bcl-2 ↑ Claudin-5 ↑ | [78] |
15 mg/kg (i.p.) | 1 d | Stroke model rat | Infarct volume ↓ Brain oedema ↓ Neutrophil invasion ↓ Apoptotic ↓ | [71] |
10 or 25 mg/kg(i.p.) | 3 d | Stroke model rat | Neurological deficits ↓ Brain oedema ↓ Infarct volume ↓ Nrf2 ↑, HO-1↑, SOD1↑, GSH ↑ NF-κB ↓, MMP-9↓, MDA ↓ | [77] |
100 or 200 mg/kg (p.o.) | 9 d | Stroke model rat | TNF-a↓, IL-1β↓, IL-6↓, NO ↓ TLR4↓, NF-κB ↓ | [80] |
1, 10, 20 or 50 µM | 24 h | Stroke cell model | Endoplasmic reticulum (ER) stress(ERS) -induced apoptosis ↓ Dehydrogenase ↓ Cellular viability ↑ PI3K/AKT pathway ↑ | [36] |
0,10,50 or 100 µM | 24 h | LPS-stimulated BV-2 microglia | TNF-a, IL-1β ↓ NF-kB ↓, ERK ↓, p38 ↓, JNK phosphorylation ↓ | [9] |
25 or 100 μg/ml | 24 h | LPS-stimulated microglia | NO↓, iNOS↓, NF-κB↓, MAPK phosphorylation ↓ | [19] |
3–10 μM | 24 h | BV‐2 cells | IL‐1β↓ | [17] |
40 μM | 20 h | LPS-stimulated BV-2 microglia | NO ↓, TNF-a ↓, IL‐1β↓, IL-6 ↓ | [1] |
100 mg/kg (p.o) | 10 d | LPS intrahippocampal challenge | Memory deficit ↓ COX-2 ↓, IL-1β ↓, TNF-α ↓, and iNOS↓ | [48] |
100 or 200 mg/kg (p.o.) | 6 w | LPS-induced neuroinflammation | iNOS↓, IL-6 ↓, JAK2↓, TNF↓, IL-1↓, and NF-κB↓ STAT3 phosphorylation ↓ | [63] |
6.25, 12.5, 25 or 50 μg/ml | 24 h | LPS-stimulated BV-2 microglia | NO↓, iNOS↓, IL-6↓, JAK2↓, TNFα↓, IL-1β↓, and NF-κB ↓ | [57] |
10, 20 or 40 μM | 24 h | H2O2-induced oxidative stress in astrocytes | Ose-regulated protein(GRP) 78 ↑, Cell death ↓ Endoplasmic reticulum (ER) stress lead ↓ | [21] |
30, 50, 100 or 200 μM | 10 min | Glutamate-stimulated neurons | Calcium overload ↓ ROS ↓ Mitochondrial depolarization ↑ | [31] |
1, 10 or 30 µM | 5 min | Neurons | ROS↓, apoptotic signalling↓, ATP production ↑, Neuronal viability↑, Nrf2↓, HO-1↓ | [3] |
10 mg/kg (i.p.) | 9 d | Cisplatin-induced nerve injury | Peroxide↓, apoptotic↓ | [25] |
50 µM | 96 h | Sodium arsenate-induced neural progenitor cells toxic | Neuronal degeneration ↓, Oedema ↓, caspase-3↓ BDNF ↑, G6PD activity ↑ Antioxidant ↑, Antiapoptotic ↑ Neuroprotective effects ↑ | [42] |