Table 1.

Neuroprotective effects of resveratrol, curcumin, and ginsenoside on PD

Agent	Mechanism	In vivo/In vitro model	Protection	References
Resveratrol	Anti-Inflammation	N9 microglial cell	Decrease the mRNA levels of IL-1α and TNF-α; Decrease the levels of COX-2 expression; Decrease the levels of NO, TNF-α, IL-1β, IL-6, MCP-1; Suppress production of IL-12p40, IL-23 and C-reactive protein, and respective receptors; Down-regulate MPO; Modulate the activity of PGC-1α, Akt and NF-κB	[10,18-21]
		6-OHDA-induced rat
		MPTP-induced mice
		Primary microglia and astrocytes
		Primary mouse astrocytes
		BV2 microglial cells
	Anti-Apoptosis	PC12 cells	Reduce the activity of caspase-3 and the level of Bax; regulate DNA fragmentation and the mRNA levels and protein expression of Bax, Bcl-2, cleaved caspase-3, and cleaved PARP-1; Activate sirtuin deacetylases and PPAR-γ	[12,24,25,27]
		SH-SY5Y cells
		HtrA2 knockout mice
		Saccharomyces cerevisiae
	Antioxidation	PC12 cells	Diminish superoxide anion; Inhibit ROS generation; Up-regulate the antioxidant status and the expression of MsrA; Activate PPAR-γ, AMPK, SIRT1; Raise the mRNA expression of PGC-1α’s target genes,	[12,37,38,41]
		SKN-MC cells
		6-OHDA-induced rat
		SH-SY5Y cells
		Primary fibroblast from PD patients with Park2 mutation Transgenic mice overexpressing PGC-1α DA SN4741 cells
	neurotrophic effect	Primary rat midbrain neuron-glia cultures	Increase neurotrophic factors release in the concentration- and time-dependent manners	[11]
Curcumin	Anti-Inflammation	MES23.5 cells	Inhibit NF-κB translocation and AP-1 activation; Inhibit the protein expression of GFAP and iNOS, decrease activation of astrocytes and microglia, reduce pro-inflammatory cytokine, alleviate loss of TH-IR fibers, protect axon	[48-52]
		Primary rat mesencephalic neuron-glia cultures
		MPTP-induced mice
	Anti-Apoptosis	PC12 cells	Reduce MMP loss, attenuate MPP(+)-induced an increase in intracellular ROS level, induce overexpression of BCl-2 and antagonize MPP+-induced overexpression of iNOS; Ease alphaS-induced toxicity; Protect DA neuron axon; Decrease the Bax/Bcl-2 ratio; Reduce the accumulation of A53Tα-synuclein; inhibit the JUN/c-Jun pathway; Block MPP(+)	[53-55,65]
		MPTP-induced mice
		SH-SY5Y cells
		Ts-1-infected mice
		A53T α-synuclein cell model
		DA neurons in Mpp(+) model
	Antioxidation	MES23.5 cells	Restore MMP, increase level of Cu-Zn superoxide dismutase, suppress ROS; Sustain SOD1 level; reduce the levels of p-p38, cleaved caspase-3 and quinoprotein formation; restore depletion of GSH levels, free radical scaveng; Inhibit oxidative stress and the mitochondrial cell death pathway; activate the Nrf2/ARE pathway; Reduce p53 phosphorylation	[48,51,57,62,64,66-68]
		6-OHDA-induced mice
		SH-SY5Y cells
		6-OHDA-induced rats
		A53T α-synuclein cell model
	Prevent α-synuclein aggregation and fibrillation	SH-SY5Y cells	Prevent α-synuclein aggregation and fibrillation; Destabilize preformed falphaS; Specifically binds to oligomeric intermediates	[60,71-74]
	Inhibit MAO-B	MPTP-induced mice	Inhibit MAO-B activity	[71,76]
Ginsenoside	Anti-Inflammation	BV2 microglial cells	Suppress NO production and TNF-α secretion, inhibit the mRNA expressions of iNOS, TNF-α, IL-1β, COX-2 and MMP-9, inhibited the phophorylations of PI3K/Akt and MAPKs and the DNA binding activities of NF-kB and AP-1; Suppress phosphorylation and nuclear translocation of NF-κB/p65, phosphorylation and degradation of IκB and the phosphorylation of IKK; inhibit the activation of Akt and ERK1/2; Reduce NO-formation and PGE2 synthesis; attenuate up-regulation TNF-α, IL-1β and IL-6 mRNA, and iNOS and COX-2 expression	[5,84-86]
		Rat primary microglia
		Mesencephalic primary cultures
		PC12 cells
		LPS-treated mice
	Anti-Apoptosis	PC12 cells	Inhibit the activation of caspase-3, reduce iNOS and NO production; Increased the phosphorylation inhibition of Bad through activation of the PI3K/Akt pathway; Enhance the expression of Bcl-2 protein and mRNA, reduce the expression of Bax, Bax mRNA, and iNOS, and attenuate the cleavage of caspase-3	[87-91]
		Primary cultured nigral neurons
		MPTP-induced mice
	Antioxidation	PC12 cells	Reduce the generation of ROS and cytochrome c release, restore MMP, increased the phosphorylation inhibition of Bad through activation of the PI3K/Akt pathway; Decrease iron influx, inhibit IRPs; decrease DMT1-mediated ferrous iron uptake and iron-induced cell damage	[87,88,90,91]
		MES23.5 cells
		Primary cultured nigral neurons
	Neurotrophin-like effects	PC12 cells	Increase neurite outgrowth; Reversed MPTP-induced cell death	[92]
		SN-K-SH cells