Extracts or Active Components from Acorus gramineus Aiton for Cognitive Function Impairment: Preclinical Evidence and Possible Mechanisms

Table 3

Characteristics of mechanism studies of EAAGA on cognition impairment.

Study (years)	Model	Method of administration (experimental group versus control group)	Observations	Possible mechanisms
Yang et al. [17]	Chronic lead-induced dysmnesia model	β-Asarone versus distilled water	Attenuated memory deficits	Arc/Arg3.1 and Wnt pathway
			Increased dendritic spine density	Increased dendritic spine density
			Up-regulated NR2B, Arc/Arg3.1, and Wnt7a protein expression
Wei et al., 2013	AβPP/PS1 double-transgenic mice	β-Asarone versus Tween 80	Improved cognitive function	CaMKII/CREB/Bcl-2 signaling pathway
			Prevents PC12 cell and cortical neuron damage	Inhibition of apoptosis
			Inhibited the apoptosis of PC12 cells and cortical neurons
Sundaramahalingam et al. [18]	Noise stress induced memory impairment model	α-Asarone versus Tween 80	Prevent memory impairment	Reduction of oxidative reactions
			Decreased hsp 70 mRNA levels
			Decreased SOD and AChE activity
			Increased CAT and G6PD activity
			Increased VC, VE, and GSH levels
Shin et al. [19]	LPS-induced cognitive handicap mode	α-Asarone versus NS	Ameliorated memory deficits	Repression of inflammatory reactions
			Reduced Iba1 protein expression	Inhibition of apoptosis
			Reduced TNF-α and IL-1β mRNA
			Reduced BACE1 expression
			Increased CA1 neurons
			Reduced TUNEL-labeled cells
Ma et al. [11]	Aβ1-42-induced AD model	Water extract versus NS	Ameliorated memory deficits	Inhibition of neurotoxicity
		Essential oil versus NS	Reduced Aβ positive cells
		Defatted decoction versus NS	Decreased DCx and nestin expression
			Decreased nestin positive cells
Liu et al. [20]	APPswe/PS1dE9 double transgenic mice	β-Asarone versus Tween 80	Improved the learning and memory ability	Regulation of synaptic plasticity
			Increased SYP and GluR1 expression
Limón et al. [21]	Aβ-induced AD model	α-Asarone versus NS	Ameliorated memory deficits	Reduction of oxidative reactions
			Decreased NO levels
Li et al. [22]	D-gal- and AlCl3-induced AD model	β-Asarone versus NS	Improved the learning and memory ability	Protection of cerebrovascular
			Increased rCBF and the activity of Na–K-ATP
			Decreased pyruvic acid contents
			Decreased ET-1, eNOS, and APP mRNA expression
Zhang et al. [5]	Aged mice	Essential oil versus Tween 80	Improved cognitive function; Increased 5-HT, NE, DA, and NE levels; Decreased AChE activity	Improvement of cognitive function
	Scopolamine-induced dysmnesia model	Essential oil versus Tween 80
	Ethanol-induced dysmnesia model	Essential oil versus Tween 80
	Aged rats	Essential oil versus Tween 80
	Sodium nitrite-induced dysmnesia model	Essential oil versus Tween 80
Lee et al. [10]	MCAO/2 h-induced cognitive impairments model	AGA versus NS	Attenuated learning and memory deficits; Increased cell density	Inhibition of apoptosis
Lee et al. [23]	Chronic corticosterone exposed	β-Asarone versus NS	Improved cognitive function; Increased BDNF and CREB expression; Increased BDNF, CREB, and Bcl-2 mRNAs levels; Decreased Bax mRNAs levels; Decreased serum levels of CORT	Inhibition of apoptosis
Kumar et al., 2012	Scopolamine-induced amnesic model	α-Asarone versus vehicle	Improved cognitive function; Increased of AchE activity; Inhibition MDA expression and SOD levels; Reduced SOD activity	Reduction of oxidative reactions
Kim et al. [25]	Ibotenic acid-induced amnesia	AGA versus NS	Ameliorated learning and memory deficits; Increased ChAT positive neurons; Increased AchE neurons	Stimulation of cholinergic system
Geng et al. [26]	Aβ1-42-induced AD rat model	β-Asarone versus NS	Ameliorated learning and memory deficits; Increased Bcl-2, Bcl-w expression; Increased Bcl-2 and Bcl-w mRNA levels; Decreased cleavage of caspase-3; Reduced caspase-3 mRNA levels; Decreased p-JNK expression	Inhibition of apoptosis
Chen et al. [27]	SAMP8 mice	β-Asarone versus NS	Improved cognitive function; Reduced ROCK, beclin1, and LC3 expression; Increased p62 expression; Increased GAP43, MAP2, and SYN expression; Increased GAP43-, MAP2-, and SYN-positive cells; Decreased lipofuscin-positive cells	Reduction of autophagy
Ma et al. [28]	Aβ-induced AD model	Water extract versus NS	Ameliorated learning and memory deficits; Decreased Aβ plaques depositions	Improvement of cognitive function
		Water extract without oil versus NS
		Essential oil versus NS
Tian et al. [29]	Aβ-induced AD model	Water extract versus NS	Ameliorated learning and memory deficits; Decreased NOS activity	Inhibition of neurotoxicity
		Defatted decoction versus NS
		Essential oil versus NS
Zhou et al. [30]	Scopola-induced AD model	Essential oil versus NS	Ameliorated learning and memory deficits; Decreased GFAP expression; Decreased MDA levels; Increased SOD levels	Reduction of oxidative reactions
Wang GM et al., 2017	Chronic restraint stress-induced cognitive impairments mode	Essential oil versus NS	Ameliorated learning and memory deficits; Increased body mass; Decreased plasma cortisol levels	Inhibition of chronic stress
Hu et al. [32]	Sodium nitrite-induced amnesic model	Essential oil versus Tween 80	Increased learning and memory deficits	Improvement of cognitive function
		Defatted decoction versus Tween 80
		α-Asarone versus Tween 80
		β-Asarone versus Tween 80
	Ethanol-induced amnesic model	Essential oil versus Tween 80	Ameliorated learning and memory deficits	Improvement of cognitive function
		Defatted decoction versus Tween 80
		α-Asarone versus Tween 80
		β-Asarone versus Tween 80
Chen et al. [33]	D-galactose-induced dementia model	Water extract versus distilled water	Ameliorated memory deficits; Decreased MDA levels; Increased SOD activity	Reduction of oxidative reactions
Gu et al. [34]	Scopolamine-induced dysmnesia mice	Water extract versus NS	Ameliorated memory deficits	Improvement of cognitive function
	NaNO2-induced dysmnesia model	Water extract versus NS	Ameliorated memory deficits
	45% ethanol-induced dysmnesia mice	Water extract versus NS	Ameliorated memory deficits; The AchE activity of mice brain was not influenced
	Scopolamine-induced dysmnesia rat	Water extract versus NS	Ameliorated memory deficits
Wu et al., 2004	Aged mice	Essential oil versus NS	Ameliorated memory deficits; Decreased AChE activity; Increased c-jun mRNA levels	Inhibition of apoptosis
	Aged mice	β-Asarone versus NS
	Aged mice	Water extract versus NS
	Ethanol-induced dysmnesia model	Water extract versus NS
	NaNO2-induced dysmnesia model	Essential oil versus NS
	NaNO2-induced dysmnesia model	β-Asarone versus NS
	NaNO2-induced dysmnesia model	Water extract versus NS	Ameliorated memory deficits
	Scopolamine-induced dysmnesia model	Essential oil versus NS
	Scopolamine-induced dysmnesia model	Essential oil versus NS
	Scopolamine-induced dysmnesia model	Water extract versus NS
Wen et al., 2009	Ethanol-induced dysmnesia model	Water extract versus NS	Ameliorated memory deficits	Inhibition of apoptosis
	NaNO2-induced dysmnesia model	Essential oil versus NS
	Scopolamine-induced dysmnesia model	Water extract versus NS
	Scopolamine-induced dysmnesia model	Essential oil versus NS
	Scopolamine-induced dysmnesia model	Water extract versus NS
	Scopolamine-induced dysmnesia model	Essential oil versus NS
Yang et al. [37]	Aβ1-42-induced AD model	β-Asarone versus NS	Improved cognitive function; Inhibited AQP4, IL-1β, and TNF-α expression; Decreased Aβ deposition; Alleviated hippocampal damage	Suppression of astrocyte activation
Zhou et al. [38]	D-gal- and AlCl3-induced AD model	α-Asarone versus NS	Improved cognitive function; Decreased Aβ and Tau protein expression; Increased ACh expression	Inhibition of apoptosis
Jiang et al. 2007	AlCl3-induced AD model	β-Asarone versus NS	Improved cognitive function; Increased SOD and GSH-Px levels; Decreased MAD levels	Reduction of oxidative reactions
Huang et al. [40]	Fragile X syndrome model	α-Asarone versus NS	Improved cognitive function	Damage of Akt pathway
Wang BL et al., 2017	Aβ1-42-induced AD model	β-Asarone versus NS	Improved cognitive function; Decreased HIF and MDA levels; Increased SOD and CAT levels	Reduction of oxidative reactions
Guo et al. [42]	Scopolamine-induced AD model	β-Asarone versus NS	Improved cognitive function	Inhibition of apoptosis
Jiang et al. [43]	STZ-induced AD model	Essential oil versus solvent	Improved cognitive function; Decreased MDA levels; Increased SOD levels	Reduction of oxidative reactions
Yang et al. [44]	PTZ-induced epilepsy model	AGA versus NS	Improved cognitive function	Inhibition of apoptosis
	PTZ-induced epilepsy model	α-Asarone versus NS	Improved cognitive function	Inhibition of apoptosis
Wang et al. [45]	Aβ1-42-induced AD model	Essential oil versus NS	Improved cognitive function	Improvement of cognitive function
Ma et al. [46]	D-gal- and AlCl3-induced AD model	β-Asarone versus NS	Improved cognitive function; Decreased GA P-43 mRNA levels; Increased SYP mRNA levels; Decreased PSD-95 mRNA levels	Regulation of synaptic plasticity

Ach: acetylcholine; AchE: acetylcholinesterase; AD: Alzheimer’s disease; AlCl₃: aluminum trichloride; ChAT: acetylcholine transferase; D-gal: D-galactose; MCAO: middle cerebral artery occlusion; MDA: malondialdehyde; STZ: streptozotocin; SOD: superoxide dismute; HIF: hypoxia-inducible factor; SYN/SYN: synaptophysin; MAP2: microtubule-associated protein 2; Aβ1-42: amyloid beta 1-42; NS: normal saline; PTZ: pent ylenetet razol; GSH-Px: glutathione peroxidase; NE: norepinephrine; 5-TH: 5-hydroxytryptamine; DA: dopamine; NOS: nitric oxide synthase; Bcl-2: B-cell lymphoma/leukemia-2.