Table 1.

Effects and mechanisms of ginsenoside Rg1 in ameliorating learning and memory impairment as reported and evidenced.

Effect	Mechanism and Descriptions	Cited references
Improving learning and memory disorder; improving performance in a passive avoidance learning paradigm	Enhancing cholinergic metabolism	[64]
Effective in improving learning and memory disorders caused by Alzheimer's disease	Reducing the amount of Abeta detected in the brains of mice; reducing the level of amyloid beta; regulating the activity of PKA/CREB; improving cognitive performance in SAMP8 mice	[65,66]
Inducing neuroprotection and ameliorating learning and memory disorders	Ameliorating amyloid pathology; modulating the amyloid precursor protein process; improving cognition; activating PKA/CREB signaling	[67]
Attenuating the generation of Aβ; improving learning and memory	Enhancing the binding of PPARγ to the BACE1 promoter; suppressing the activity of BACE1; increasing the expression of IDE	[81,82]
Reducing okadaic acid-induced spatial memory impairment; preventing Aβ formation	Through the GSK3β/tau signaling pathway	[68]
Restoring hippocampal long-term potentiation and memory	Promoting the clearance of AD-related proteins; activating the BDNF-TrkB pathway	[69]
Improving behavioral deficits in AD mice	By regulating the expression of CPLX2, SYN2, and SNP25 proteins	[83]
In response to the senescence of neuronal cells; ameliorating learning disabilities in aged rats	Reversing tert-butyl hydroperoxide-induced morphological changes; promoting expression of synaptic plasticity-related proteins; regulating the PI3K/AKT pathway	[[70], [71], [72]]
Protecting against neural stem cell senescence	Ameliorating D-galactose-induced cognitive impairment; reducing oxidative stress; downregulating the Akt/mTOR signaling pathway	[73]
Ameliorating cognitive deficits in aging mice induced by D-galactose and AlCl3	Restoring FGF2-Akt and BDNF-TrkB signaling axis; inhibiting apoptosis	[74]
Alleviating learning and memory impairments induced by painkillers and other chemicals	Improving spatial learning capacity impaired by morphine; restoring morphine-inhibited long-term potentiation	[84]
Effectively improving memory impairment induced by scopolamine		[85]
Inhibiting mitochondrial dysfunction; exerting antioxidant, anti-inflammatory, and anti-apoptotic effects	Ameliorating isoflurane-induced caspase-3 activation; attenuating isoflurane/surgery induced neurocognitive impairment and Sirt3 dysfunction	[[86], [87], [88]]
Ameliorating lipopolysaccharide-induced cognitive impairment	Through regulation of the cholinergic system	[89]
Protecting against neuronal degeneration induced by chronic dexamethasone	By inhibiting mouse NLRP1 inflammatory cytokines	[90]
Ameliorating cognitive deficits induced by repeated alcohol intoxication	Modulating NR2B-containing NMDARs and excitotoxic signaling	[91]
Rg1 showed good effects against neurological functions, neural structures, and neurophysiological aspects affecting learning and memory	Ameliorated chronic restraint stress-induced learning and memory deficits by reducing reactive oxygen species (ROS) production, reducing neuronal oxidative damage in mouse frontal cortex and hippocampal cornu ammonis 1 (CA1), inhibiting the expression of NADPH oxidase 2 (NOX2), neutrophil cytosol factor 1 (p47phox), and ras-related c3 botulinum toxin substrate 1 (RAC1).	[92]
Modulated firing in the medial prefrontal cortex of rats and inhibited hippocampo-medial prefrontal cortical long-term potentiation.	Rg1 ameliorated the learning and memory deficits induced by chronic restraint stress in rats by mediating the BDNF/TrkB/extracellular signal-regulated kinase (Erk) pathway in the prefrontal cortex.	[93,94]
Rg1 acts similarly to growth factors in promoting the proliferation and differentiation of neural stem cells.	May reduce cognitive impairment induced by cardiac arrest by regulating neuroinflammation and hippocampal plasticity.	[95,96]
Promotes remyelination and functional recovery in demyelinating diseases by enhancing oligodendrocyte progenitor cell-mediated remyelination, improving spatial memory, motor function, and anxiety-like behavior in mice.	Promotes glutamate release, possibly through a Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway, to regulate central nervous system neurotransmitters to enhance learning and memory.	[97,98]
Reduces PTSD-like behaviors in mice by reducing corticosterone and corticotrophin-releasing hormone levels.	Has a protective effect on PTSD-like behavior in mice by promoting synaptic proteins and reducing inward rectifying potassium channel 4.1 (Kir4.1) and tumor necrosis factor alpha (TNF-α) in the hippocampus.	[79,80,99]
Potential application in the treatment of learning and memory disorders in postmenopausal women.	Can prevent cognitive impairment and hippocampal neuronal apoptosis in vascular dementia mice, probably by promoting g protein-coupled receptor 30 (GPR30) expression.	[[75], [76], [77]]