TABLE 4.

Summary of the targets/pathways/mechanisms and effects of gastrodin on neurodegenerative disorder.

Disease		Inducer	Experimental model		Dose		Targets/mechanisms		Effects			Refs
AD		In vitro: Aβ1-42 (10 μM)	In vitro: hippocampal neurons		In vitro: 0, 0.1, 0.3, 1, 3, 10, 30, 100, 300 μM		In vitro: mRNA and protein expression of SOD, Nrf2↑		Protects hippocampal neurons against Aβ (1–42)-induced neurotoxicity by activation of ERK1/2 signaling pathway			Zhao et al. (2012)
							The content and mRNA expression of CAT↑
							protein expression of ERK1/2, p-ERK1/2↑
AD		In vivo: NA	In vivo: Tg2576 transgenic mice		In vivo: 60 mg/kg		In vivo: SOD, CAT↑		Inhibits BACE1 expression under oxidative stress conditions by inhibition of the PKR/eIF2α signaling pathway			Zhang et al. (2016)
							MDA, BACE1↓
							The ratio of p-PKRThr446/PKR, p-eIF2αSer51/eIF2α↓
		In vitro: NA	In vitro: SH-SY5Y cells		In vitro: 25, 50 μM		In vitro: P-PKRThr446, P-eIF2αSer51↓
AD		In vitro: D-galactose	In vivo: mice		In vivo: 3, 90, 210 mg/kg (i.g.)		In vivo: mRNA expression of BDNF↑		Alleviates neuron inflammation of the AD mouse model via partly targeting the microbiota–gut–brain axis			Fasina et al. (2022)
							protein expression of TLR4, p-IκBα↓, LPS, IL-1β, TNF-α, IL-6↓
							ZO-1, occludin↑
AD		In vivo: LPS (2 mg/kg)	In vivo: C57BL/6 mice		In vivo: 100 mg/kg (i.p. injection)		In vivo: protein expression of p-Stat3, p-NF-κBp65, TLR4, TRAF6↓		Alleviates neuroinflammation in AD model mice through inhibition of the TLR4/TRAF6/NF-κB signaling pathway and activation of microglia and astrocytes			Wang et al. (2024)
							levels of Iba1, GFAP↓
							mRNA and protein expression of TNF-α, IL-1β↓
							mRNA of Arg-1↑
AD		In vitro: LPS (1 μg/mL)	In vitro: BV-2 cells		In vitro: 1, 10 μg/mL		In vitro: iNOS, CD206↑					Wang et al. (2024)
							p-Stat3, NF-κBp65↓
PD		In vivo: rotenone (2 mg/kg/d)	In vivo: Wistar rats		In vivo: 0.2 g/kg/d (i.g.)		In vivo: TH↑		Exerts a protective effect on dopaminergic neurons by reducing the expression of pro-inflammatory factors			Li et al. (2012)
							TNF-α, IL-1β, IL-6↓
PD		In vivo: MPTP (30 mg/kg/day)	In vivo: C57BL/6 mice		In vivo: 10, 30, 60 mg/kg (i.g.)		In vivo: TH, SOD↑		Restores TH levels and GFAP expression and protects dopamine neurons from neurotoxicity			Kumar et al. (2013)
							GFAP, cleavage PARP, caspase-3↓
							mRNA expression of Bcl-2↑
							mRNA expression of Bax and the ratio of Bax/Bcl-2↓
		In vitro: MPTP (30 mg/kg/day)	In vitro: SH-SY5Y cells		In vitro: 1, 5, 25 μM		In vitro: cleavage PARP, ROS↓
							SOD↑
							mRNA expression of HO-1, Bax, Bax/Bcl-2↓
							mRNA expression of Bcl-2↑
PD		In vivo: MPTP	In vivo: C57BL/6 mice		In vivo: 60 mg/kg (i.p. injection)		In vivo: mRNA and protein expression of HO-1, GSH, SOD, Nrf2↑		Activates the ERK1/2 signaling pathway and promotes nuclear translocation of Nrf2 to play an antioxidant role			Wang et al. (2014)
							protein expression of p-ERK1/2↑
							protein expression of MDA↓
PD		In vivo: 6-OHDA (8 μg/2 μL/rat)	In vivo: Wistar rats		In vivo: 20, 40, 80 μg/3 μL/rat		In vivo: The activity of MPO↓		Reduces peroxidase activity, lipid peroxidation levels, NO production, and restores TAC levels to alleviate PD.			Haddadi et al. (2018)
							level of MDA, NO↓

AD, Alzheimer’s disease; Aβ, beta-amyloid; SOD, superoxide dismutase; Nrf2, nuclear factor erythroid 2-related factor 2; CAT, catalase; ERK, extracellular regulated kinase; NA, not applicable; MDA, malondialdehyde; BACE1, β-site APP, cleaving enzyme 1; PKR, protein kinase; eIF2α, eukaryotic initiation factor-2a; BDNF, brain-derived neurotrophic factor; TLR4, toll-like receptor 4; IκBα, Inhibitor of kappa B-α; LPS, lipopolysaccharide; IL, interleukin; TNF-α, tumor necrosis factor-α; ZO-1, zonulin-1; Stat3, signal transducer and activator of transcription 3; NF-κB, nuclear factor-κB; TRAF6, tumor necrosis factor receptor-associated factor 6; GFAP, glial fibrillary acidic protein; Arg-1, arginase-1; iNOS, inducible nitric oxide synthase; PD, Parkinson’s disease; TH, tyrosine hydroxylase; MPTP, 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine; PARP, poly ADP-ribose polymerase; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma-2; 6-OHDA, 6-hydroxydopamine; GSH, glutathione; MPO, myeloperoxidase; SD, Sprague-Dawley; NO, nitric oxide.