Table 2.

Pharmacological mechanism of Curcumin on Neurological disorders.

Disease	Research object	in vitro in vivo	administration route	Mechanism of action	Results	Refs
AD and PD	Protein tau	in vitro	-	↓the aggregation and oligomerization of tau	Inhibited the aggregation of tau and dissolved the tau aggregates	[88]
AD	N2a/WT cells, N2a/ APP695swe cell and six-month-old APP/PS1 double transgenic mice	in vitro in vivo	p.o.	↓Caveolin-1↓ GSK-3β	Attenuate the hyper-phosphorylation of Tau	[89]
AD	SH-SY5Y (human neuroblastoma cells) and HEK293 (human kidney cells)	in vitro	-	↑ERβ directly effects on the upstream factors of the NFκB signaling pathway	Notably reduce Aβ levels and inhibits BACE1gene expression	[90]
AD	Adult male and female APPswe/PS1dE9 mice	in vivo	i.v.	↓amyloid deposition ↓Aβ aggregation ↓soluble Aβ40 ↑ oluble Aβ42	Reverses existing amyloid pathology and associated neurotoxicity	[91]
AD	Tg2576 mice (B6; SJLTg (APPSWE) 2576Kh) with the APP Swe transgene); THP-1 cells	in vitro in vivo	p.o.	↓ CD33↑TREM2 ↑ TyroBP ↓miR-155↓genes characteristic of toxic pro-inflammatory M1 microglia (CD11b, iNOS, COX-2, IL-1β)	Stimulate phagocytic clearance of amyloid while restore neuro-inflammatory networks	[92]
AD	Amyloid-β (Aβ1 -40) induced AD rat models	in vivo	i.p.	↓GFAP mRNA and the number of GFAP positive cells ↓AS activity	Improves the spatial memory disorders in Aβ1-40-induced rats	[93]
AD	APPswe/PS1 dE9 double transgenic mice	in vivo	i.g.	↑ insulin like growth factor (IGF)-1R, IRS-2, PI3K, p-PI3K, Akt and p-Akt protein expression ↓ IR and IRS-1	Improve spatial learning and memory by increasing glucose metabolism and ameliorating the impaired insulin signalling pathways in the brain	[95,96]
PD	An PD mice model induced by rotenone	in vivo	p.o.	↑mitochondrial enzyme complex activities ↓acetylcholine esterase enzyme level ↑activities of antioxidant enzymes	Improve behavioral alterations and have antioxidant potential in vivo.	[97]
PD	Transgenic fly lines that express wild-type human synuclein (h-αS)	in vivo	p.o.	↓lipid peroxidation ↓protein carbonyl content↓mean gray scale values	Improve the loss of activity pattern, reduce the oxidative stress and apoptosis, and prolong lifespan to a certain extent.	[98]
PD	Adult male C57BL/6 mice; Mouse brain and the 1RB3AN27 (N27) rat dopaminergic neuronal cell line	in vitro in vivo	i.p.	↑GSH levels ↑ γ-GCL gene expression ↑ formation of the EpRE complex and the AP1 transcription factor	Protects mouse brain against GSH depletion-mediated oxidative stress in vivo and in vitro	[99]
PD	A 6-Hydroxydopmine-Induced Rat Model of PD	in vivo	p.o.	↑the function of α7-nAChRs expressed	Neuroprotective effect via an α7-nAChR-mediated mechanism.	[100]
PD	A rat model of PD induced by LPS	in vivo	i.p.	↓transcription factor NFjB ↓proinflammatory cytokines (TNF-α, IL-1β, and IL-1α) ↓inducible nitric oxide synthase (iNOS)↓ regulating molecules of the intrinsic apoptotic pathway (Bax, Bcl-2, Caspase 3 and Caspase 9)	Modulate the aggregation of a-synuclein in vitro and in vivo.	[101]
PD	Male, albino, NMRI rats brain mitochondria	in vitro	-	Preventing mitochondrial HKI release and ROS enhancement induced by α-synuclein fibrillation products	Ameliorate neurodegenerative disorders in PD.	[102]
PD	SH-SY5Y cells	in vitro	-	↓phosphor-mTOR and phosphor-p70S6K↓the accumulation of A53T α-synuclein	Reduce the accumulation of A53T α-synuclein through the mTOR/ p70S6K signaling and recovery of macroautophagy	[103]
PD	6-hydroxydopamine (6-OHDA)-PD rat model	in vivo	p.o.	↑ hippocampal brain derived neurotrophic factor (BDNF), ↑TrkB, ↑phospha-tidylinositide 3-kinases (PI3K)	Promoting neural regeneration of hippocampal tissue	[104]
PD	SH-SY5Y neuroblastoma cells knocked down of PINK1 via siRNA	in vitro	-	↑ cell viability and maximal respiration ↑mitochondrial membrane potential (MMP)↓apoptosis	Prevent mitochondrial dysfunction and apoptosis in PINK1-deficient cells.	[105]
Depression	Chronic unpredictable mild stress (CUMS)-induced depression rat model	in vivo	p.o.	↓NF-κB P65↑IkB↓ IL-1β, IL-6 and TNF-α↓P2X7R, NLRP3, and Caspase-1 P20↓pro-IL-1β and mature-IL-1β↓indolamine-2, 3-dioxygenase (IDO) expression↓KYN content and the KYN/TRP ratio↑5-HT content	Alleviate depression by inhibiting the NLRP3 inflammasome and kynurenine pathway.	[106]
post-stroke depression (PSD)	SD rats of PSD model	in vivo	p.o.	↓Ca2+channel ↓P2X7R ↓TNF-α ↓IL-1β	Block Ca2+ accumulation and neuroinfammation by inhibit P2X7R activity	[107]
Depression	CUMS-induced depression rat model	in vivo	i.p.	↓Iba-1↓GFAP↓IL-1β ↓TUNEL positive cell ↑NeuN positive cell	Alleviated depression-like behaviors, expression of the proinflammatory cytokine interleukin-1β (IL-1β) and inhibited neuronal apoptosis within neurons of the ventromedial prefrontal cortex (vmPFC)	[108]
Depression	CUMS-induced depression rat model	in vivo	p.o.	↓oxidative stress markers (Nox2, 4-HNE, and MDA) ↑ activity of CAT ↑mRNA expression of NQO-1 and HO-1	Curcumin could alleviate the oxidative stress via Nrf2-ARE signaling pathway to improve depressive-like state.	[109]
Depression	Adult rats exposed to a regime of chronic stress	in vivo	p.o.	↑5-HT1A mRNA and BDNF protein levels	Increased hippocampal neurogenesis in chronically stressed rats, prevented the stress-induced decrease in 5-HT1A mRNA and BDNF protein levels in the hippocampal subfields	[110]
Depression	Adult male Wistar Kyoto (WKY) rat, a putative model of depression	in vivo	i.p.	Reduction of immobility in the forced swim test (FST); increase in hippocampal brain derived neurotrophic factor (BDNF)	Antidepressant-like effect by increased neurotrophic activity	[111]
Depression	CUMS-induced depression rat model	in vivo	i.p.	↑expression of synapse-associated proteins (such as brain-derived neurotrophic factor, PSD-95 and synaptophysin)and LA synaptophysin	Neuroprotection and antidepressant-like effects in the CUMS induced depression model.	[112]
Depression	Olfactory bulbectomy and forced swimming test models of depression in male albino rats	in vivo	p.o.	↑serotonin, dopamine, and noradrenaline ↓3, 4-dihydroxyphenylacetic acid and 5-hydro-xyindoleacetic acid	Exert antidepressant activity in the olfactory bulbectomy and forced swim test model of depression through monoaminergic neurotransmitter pathway	[113]