Table 1.
Neuropharmacological mechanisms of naringenin against different type of neurodegenerative diseases.
| Type of Diseases | Method | Model | Neuropharmacological Mechanisms and Outcome | References |
|---|---|---|---|---|
| LPS Induced neuroinflammation | In vitro: BV2 microgelia cells | ↓iNOS ↓COX-2 ↑SOCS3 ↑ AMPKα ↑ PKCδ | [85] | |
| Neuroinflammation | Induced by LPS | In vitro: BV2 microgelia cells | ↓JNK ↓ERK ↓p38 ↓MAPK ↓TNF-α ↓IL-1β ↑ Arg-1↑IL-10 | [12] |
| Induced by LPS | In vitro: BV2 microgelia cells | ↓TNF-α ↓IL-6 ↓IL-1β ↓MCP-1 ↓NfκB ↓MAPK ↓Akt ↓iNOS ↓ COX-2 | [86] | |
| Induced by LPS/ IFN-γ | In vitro: microglia | ↓p38 MAPK ↓ERK1/2 ↓STAT1 ↓iNOS ↓ TNF-α | [87] | |
| Aβ25-35-induced AD | In vitro: PC12 cells | ↓apoptosis, ↓caspase3, ↑ PI3K/AKT, ↑ER | [54] | |
| AD | Aβ25-35-induced AD | In vivo: Wistar rats | ↓MDA ↓apoptosis, ↑ER, ↑spatial memory and cognition | [55] |
| ICV-STZ- induced AD Induced by Aβ1-42 and Aβ25-35 |
In vivo: Sprague–Dawley rats In vitro: cultured cortical neurons In vivo: 5XFAD Mice |
↓Tau hyper-phosphorylation, ↑ PI3K/AKT ↓GSK3-β ↑ PPAR- γ ↑insulin signaling ↑spatial learning and memory ↓amyloid plaques, ↓Tau hyper-phosphorylation | [52] [56] |
|
| Amnesia | Induced by scopolamine | In vivo: ICR mice | ↓AchE activity ↑spontaneous alteration behavior |
[62] |
| pMCAO- induced cerebral ischemic | In vivo: Sprague–Dawley rats | ↓infarct size, ↓brain water content, ↓ NOD2, RIP2, NF-κB, MMP-9, ↑ claudin-5 | [152] | |
| Induced by hypoxia | In vitro: neurons isolated from the brain of Sprague–Dawley rats | ↓ROS, MDA, ↑SOD, GSH↓caspase-3, Bax, ↑ Bcl-2, ↑AMP, ADP, ATP, ANT↑ Nrf2, HO-1, NQO1 | [160] | |
| Ischemic stroke | MCAO/R-induced ischemic stroke | In vivo: Sprague–Dawley rats | ↓brain water content, ↓TUNEL-positive cells | [163] |
| Induced by MCAO/R | In vivo: Wistar rats | ↓infarct size, neurological deficits, brain water, ↑ motor, and somatosensory function ↑SOD, GSH, MPO, TBARS, ↓COX-2, iNOS, ↓IL-1β, TNF-α ↓ NF-κB | [155] | |
| Diabetic retinopathy | STZ-induced diabetic retinopathy | In vivo: Wistar albino rats | ↓ TBARS, ↑GSH, ↓caspase-3, Bax, ↑Bcl-2 ↑ BDNF, TrkB, synaptophysin, | [169] |
| Polyglutamine diseases | - | In vitro: mouse C3H10T1/2 cells, COS-7 cells, and HeLa-tetQ97 Cells | ↑GRP78 | [175] |
| (MOG)35-55-induced EAE | In vivo: C57BL/6 mice | ↓ Th1, Th9, Th17, ↑ Treg, ↓T-bet, PU.1, and RORγt, | [97] | |
| EAE | Induced by anti-CD3/CD28 | In vivo: C57BL/6 mice | ↓IFNγ, ↓STAT1, STAT3, STAT4, ↓IL-6, ↑gp-130, ↓Foxp3 | [101] |
| Induced by anti-CD3/CD28 and (MOG)35-55 | In vitro: mouse T cells | ↓T cells proliferation, ↓ IFN-γ, IL-17A ↓ TNF-α, IL-6, block T cells at G0/G1 phase ↑ P27, ↓ retinoblastoma protein phosphorylation, ↓IL-2, CD25 ↓ STAT5 | [104] | |
| Induced by 6-OHDA | In vitro: Human neuroblastoma SH-SY5Y cells. In vivo: C57BL/6 mice | ↑Nrf2/ARE ↑HO-1, ↓ROS ↑GSH ↓ JNK and p38 | [71] | |
| PD | MPTP-induced PD | In vivo: C57BL/6J mice | ↓α-synuclein ↑dopamine transporter ↑DOPAC ↑HVA ↑TH ↓TNFα & IL1β ↑SOD | [78] |
| Rotenone-induced PD | In vivo: Wistar rats | ↓ubiquitin and caspase3 improvement of motor skills ↑parkin ↑CHIP ↑PARK 7 protein ↑TH | [76] | |
| MPTP-induced PD | In vivo: C57BL/6J mice | ↑GRx & CAT ↓LPO& iNOS ↓ nuclear pigmentation and cytoplasmic vacuolation | [80] | |
| - | In vitro: primary rat midbrain neuron-glia co-cultures | ↑ BDNF, GDNF↑ Nrf2 ↑Dopaminergic neurons survival | [73] | |
| 6-OHDA-induced PD | In vivo: Sprague-Dawley rats | ↑DOPAC, ↑HVA, ↑Dopamine↑TH | [74] | |
| Induced by MPP+ | In vitro: Human neuroblastoma SH-SY5Y cells | ↓ ROS ↓NF-κB ↓TNF-α ↓Bax ↑Bcl-2 | [79] | |
| Induced by sodium tungstate | In vivo: Wistar rat | ↑GSH ↓ROS ↓ TBARS ↑Dopamine | [141] | |
| Induced by glutamate | In vitro: primary culture of mouse hippocampal neurons | ↑ Erk1/2 & Akt phosphorylation ↓calpain-1 & caspase-3 | [144] | |
| Neurotoxicity | Induced by hypobaric hypoxia | In vivo: Swiss albino mice | ↓HIF1a ↓VEGF ↓caspase-3 ↓ ubiquitin ↑CHIP ↑ parkin |
[137] |
| iron-induced neurotoxicity | In vivo: Wistar rat | ↑ SOD, CAT ↓ROS ↑ AChE ↓MDA ↑Na+/K+ ATPase | [139] | |
| Induced by oseltamivir | In vivo: Wistar rat | ↑FABP7 ↑Ca ATPase, ↑TAC ↓TOC ↓TNO ↓ cytochrome P450 | [146] | |
| Induced by iron | In vivo: Wistar rat | ↓ROS ↑GSH, CAT, SOD ↑AchE ↑ectonucleotidase enzymes ↑mitochondrial complex I–V enzymes ↑ mitochondrial membrane potential | [140] | |
| Induced by carbaryl | In vitro: mouse neuroblastoma cells | ↓ROS ↓Bax, caspase-3 ↑Bcl-2 ↑mitochondrial membrane potential | [138] | |
| Induced by ICV-STZ | In vivo: Wistar rats | ↑ Learning and memory performance | [116] | |
| Induced by ICV-STZ | In vivo: Wistar rats | ↑learning & memory ↓TBARS, MDA, 4-HNE, H2O2, protein carbonyl, ↑GSH, SOD, CAT ↑Na+/K+ ATPase activity |
[119] | |
| Induced by scopolamine | In vivo: albino Wistar rats | ↓AChE ↑GSH ↓TBARS ↓TNFα ↓5HT, NE ↑spontaneous alternation performance & conditioned avoidance response | [118] | |
| Induced by isoflurane | In vivo: Sprague–Dawley rats | ↓Bad, caspase-3, Bax ↑ Bcl-2, Bcl-xL ↓TUNEL ↑ PI3K/Akt ↓PTEN ↓NF-κB, TNF-α, IL -6, IL-1β, Improvement of cognitive dysfunction | [123] | |
| Induced by LPS | In vivo: albino Wistar rats | ↓TLR4, NF-κB, TNF-α, COX2 and iNOS ↑Nrf2, SOD, CAT, and GSH ↓MDA and AChE ↓GFAP ↑ spatial recognition memory, discrimination ratio & retention and recall capability | [110] | |
| Cognitive deficit | Age-induced cognitive deficit | In vivo: Sprague–Dawley rats | ↑ SIRT1 ↓ NF-κB ↑serotonin, noradrenaline, dopamine, TH | [126] |
| Induced by MeHg | In vivo: Swiss Albino mice | ↑ mitochondrial complex I- IV activities, ↓lesions /10kb ↑GSH, GST ↓MDA & protein carbonyl ↑spatial and recognition memory | [131] | |
| - | In vivo: young adult male Albino Wistar rats | ↓AChE, ↑ 5HT | [120] | |
| Induced by type 2 diabetes mellitus | In vivo: Young Sprague–Dawley rats | ↓AChE, ↓hyperglycemia ↑memory performance | [115] |