Table 2.

Pharmacological effects of GE and its components on neurodegeneration.

Target pathway	Inducer(s)	Extracts/components	Dose/route/regimen	Animals or cells	Histological and biochemical evaluation	References
Neurotransmission	PTZ	EFME of GE rhizome	500 mg/kg, p.o., for 10 days	SD rats	Recovery of brain GABA contents	[30]
Neurotransmission	Stroking of the back	Gastrodin	60 mg/kg, p.o., for 1 week	Mongolian gerbils	Decreased GABA-T immunoreactivity Decreased SSADH, SSAR immunoreactivity	[57]
Neurotransmission	Cocaine	GE rhizome—methanol extract	500 or 1000 mg/kg, p.o., 5 times every 12 h before cocaine treatment	C57BL/6J mice	Attenuation of cocaine-induced seizure via GABAA, but not GABAB receptor activation	[29]
Neurotransmission	Pentobarbital	GE rhizome—ethanol extract	25, 50, and 100 mg/kg, p.o., 1 h before pentobarbital injection	ICR mice, primary culture of cerebellar granule cells	Prolonged total sleep time Reduced sleep latency Increased GAD and GABAA receptor subtype expression	[58]
Neurotransmission and antioxidation	Transient global ischemia	Vanillin, 4-HBAL, and 4-HBA	40 mg/kg, s.c., 30 min before and 30 min, 3, 6, 9, and 24 h after ischemia 0.016, 0.08, 0.4, 2, and 10 μM, for 2 h	Mongolian gerbils, PC12 cells	Downregulated 8-OHdG immunoreactivity Increased GABA-T in the early stage after ischemia Antioxidant activity on lipid peroxidation	[38]
Antioxidation	Glutamate	Gastrodin	0.1, 1, and 10 μM	PC12 cells	Inhibited ROS production Inhibited MDA, MMP, and SOD levels Blocked glutamate-induced [Ca2+]I influx Blocked CaMKII, ASK-1, and phosphorylation of MAPK	[59]
Antioxidation	MPP+	Gastrodin	1, 5, and 25 μM, 4 h prior to MPP+ exposure	SH-SY5Y cells	Decreased ROS production Induced HO-1 expression through p38 MAPK/Nrf2 signaling pathway	[54]
Antioxidation	MPP+	GE rhizome—ethanol extract	10, 100, and 200 μg/mL, 4 h prior to MPP+ exposure	SH-SY5Y cells	Inhibited ROS production Inhibited Bax/Bcl-2 ratio, cleaved caspase-3, and PARP proteolysis	[53]
Antioxidation	MPP+	GE rhizome—ethanol extract Vanillyl alcohol	10, 100, and 200 μg/mL 1, 10, and 100 μM	MN9D cells	Inhibited ROS production Inhibited Bax/Bcl-2 ratio, cleaved caspase-3, and PARP proteolysis	[55]
Antioxidation	Aβ (25–35)	GE rhizome—aqueous extract	20 μM, for 48 h	PC12 cells	Decreased ROS production Upregulated enzymatic activities of catalase, SOD, and glutathione peroxidase	[60]
Antioxidation	MCAO	GE rhizome—aqueous extract 4-HBA	500 mg/kg, i.p. 25 mg/kg, i.p., 3 days prior to MCAO	SD rats	Increased levels of genes related to antioxidant system (protein disulfide isomerase and 1-Cys peroxiredoxin)	[61]
Anti-inflammation	CUS	Gastrodin	50, 100, and 200 mg/kg, i.p., for 14 days 5, 10, 20, and 50 μg/mL	SD rats Primary hippocampal cells	Upregulated neural stem cell proliferation Reduced NF-κB and IL-1β	[62]
Anti-inflammation	LPS	Gastrodin	30, 40, and 60 μM, 1 h prior to LPS exposure	BV-2 cells	Decreased levels of proinflammatory enzymes (iNOS, COX-2) and proinflammatory cytokines (TNF-α, IL-1β) Reduced phosphorylation of ERK1/2, JNK, p38 MAPK, and CREB	[63]
Anti-inflammation	Rotenone	Gastrodin	0.2 g/kg, p.o.	Wistar rats	Suppressed microglial activation Reduced IL-1β expression	[64]
Anti-inflammation	KA	GE rhizome—ethanol extract	0.5, 1 g/kg, p.o., 30 min prior to KA injection	SD rats	Decreased microglial activation (ED1) Reduced nNOS activation	[65]
Anti-inflammation and antioxidation	LPS	GE rhizome—ethanol extract	0.25, 0.5, and 1 μg/mL, for 24 h	RAW264.7 cells	Inhibited NO production Reduced iNOS and COX-2 expression	[66]
Anti-inflammation and antioxidation	LPS	GE rhizome—ethanol extract 4-HBA	1, 10, and 100 μg/mL 50, 100, and 200 nM	BV-2 cells	Inhibited JNK and NF-κB signaling pathways Inhibited NO and iNOS	[18]

4-HBA: 4-hydroxybenzyl alcohol; 4-HBAL: 4-hydroxybenzaldehyde; 8-OHdG: 8-hydroxy-2′-deoxyguanosine; ASK-1: apoptosis signal-regulating kinase-1; CaMKII: Ca²⁺/calmodulin-dependent kinase II; COX-2: cyclooxygenase-2; CUS: chronic unpredictable stress; EFME: ether fraction of methanol extract; ERK: extracellular signal-regulated kinase; GABA-T: gamma aminobutyric acid transaminase; GAD: glutamate decarboxylase; GE: Gastrodia elata; GREE: Gastrodia elata rhizome ethanol extract; iNOS: inducible nitric oxide synthase; JNK: c-jun N-terminal kinases; KA: kainic acid; LPS: lipopolysaccharide; MAPK: mitogen-activated protein kinase; MCAO: middle cerebral artery occlusion; MDA: malondialdehyde; MMP: mitochondrial membrane potential; nNOS: neuronal nitric oxide synthase; NO: nitric oxide; PTZ: pentylenetetrazole; ROS: reactive oxygen species; SOD: superoxide dismutase; SSADH: succinic semialdehyde dehydrogenase; SSAR: succinic semialdehyde reductase.