Table 1.

Potential effects of ginseng and its active compounds through the MAPK and NF-κB pathways.

Ginseng/active compounds	Models	Major effects	References
Rb1	Aβ25-35-induced embryo rat cortical neurons	Different doses attenuate tau protein hyperphosphorylation and the expression of JNK/p38 MAPK in the process.	[74]
	MPP+-treated PC12 cells	Improves ERK1/2 phosphorylation levels and reduced phosphorylated p38 or SAPK/JNK.	[75]
Rd	PC12 cells	Helps the neurite outgrowth through upregulating the growth associated protein 43 expression through ERK-dependent signaling pathways.	[76]
	Spinal cord injury in rat	Produces neuroprotective activity by efficiently inhibiting the activation of the MAPK signaling pathway.	[77]
	APP transgenic mice	By inhibiting the transcription activity of NF-κB, might improve learning and memory when APP is used. Moreover, by suppressing the activated NF-κB pathway, further reduces the pro-inflammatory cytokines and generates protective factors.	[87]
Rg1	Aβ25–35-induced NG108-15 cells	Reduces the increased expressions of both TLR3 and TLR4.	[69]
	RSC96 cells	Produces the proliferative effects through the MAPK signaling–dependent pathway.	[78]
	BV-2 microglial cells	Attenuates the overactivation of phosphoinositide phospholipase C-γ1 and produces the inhibitory effect on the ERK1/2, JNK and p38 MAPK phosphorylation.	[79]
	Aβ25–35-induced cultured hippocampal neurons	Improves neurite outgrowth and defends against damage, and the mechanism may comprise the activation of ERK1/2 signaling.	[80]
	PC12 cells	By CaMKIIα, it activates the ERK/MAPK pathway.	[81]
	H2O2-induced PC12 cells	Normalizes the oxidative stress-induced NMMCH IIA overexpression. Regarding the collected data, NMMHC IIA-NF-kappa B/p65 pathway involved in oxidative stress-induced cell death.	[91]
Rg3GE	Scopolamine-induced mice	Suppresses the increase in acetylcholinesterase activity and stimulation of the NF-κB pathway (i.e., phosphorylation of p65) in the hippocampus.	[88]
Rg5	LPS-stimulated BV-2 microglial cells and rat primary microglia	Inhibits the phosphorylation of MAPKs and the DNA binding activities.	[82]
Rh1	LPS-induced microglia	Without affecting NF-κB DNA binding, it inhibits NF-κB–mediated transcription. In addition, due to the NF-κB–mediated transcription, an increase of cAMP responsive element-binding protein might have been identified.	[90]
Re	LPS-induced BV-2 microglia	Produces the neuroprotective events through the phospho-p38, iNOS and COX-2 signaling pathways.	[89]
RMO	LPS-induced RAW 264.7 macrophages	Reduces the p38 MAPK and its upstream kinases including MAPK kinases 3/6 (MKK3/6) phosphorylation.	[70]
	LPS-induced RAW 264.7 macrophages	Reduces the iNOS and COX-2 at both mRNA and protein levels, blockade of nuclear translocation of the p65 subunit. Henceforth, due to the inhibition of NF-κB transcriptional activity, it might have produced this anti-inflammatory effect.	[70]
Ginseng Pectin	H2O2-induced apoptosis in cortical neuron cells and U87 cells	Pretreatment enhances the phosphorylation of both the extracellular signal-regulated kinases 1 and 2 (ERK1/2).	[71]
AuNPs	LPS-induced RAW 264.7 cells	Exerts anti-inflammatory effects through the suppression of NF-κB signaling pathway activation through p38 MAPK.	[72]
	LPS-induced RAW 264.7 cells	Decreases inflammatory mediators such as NO, prostaglandin E2, interleukin-6 and tumor necrosis factor-α, expression.	[72]
Gintonin	LPS-induced RAW 264.7 cells	Produces anti-inflammatory activity via the signal transduction through MAPK, and potently suppresses the nitric oxide production and also efficiently suppressed the proinflammatory cytokines levels.	[73]
	LPS-induced RAW 264.7	Effectively suppresses the NO production without any cytotoxicity and also proficiently suppresses the proinflammatory cytokines levels. Furthermore, facilitates signal transduction through NF-κB pathways and recovers the mir-34a and mir-93 levels.	[73]
NGR1	H2O2-induced PC12 cells	Produces neuroprotective activity the effect by inducing an estrogen receptor-dependent ERK1/2 pathway.	[83]
Compound K	Phorbol myristate acetate–mediated human astroglioma cells	Significantly suppresses the p38 MAPK, ERK, and JNK activation, which are upstream modulators of activator protein-1.	[84]
Ginseng	Advanced glycation end product– induced AD in rat	Shows neuroprotective effects through the significant decreasing the expression of receptor for advanced glycation end-products and NF-κB.	[86]

AD, Alzheimer's disease; APP, amyloid β-protein precursor; AuNPs, synthesized gold nanoparticles; CaMKIIα, calcium/calmodulin-dependent protein kinase type II alpha chain; JNK, c-Jun N-terminal kinase; LPS, lypopolysaccharide; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa-light-chain-enhancer of activated; NGR1: notoginsenoside R1; NMMCH IIA, nonmuscle myosin heavy chain IIA; NO, nitric oxide; Rg3GE, Rg3-enriched ginseng extract; RMO, Red ginseng marc oil; SAPK, stress activated protein kinase; TLR, toll-like receptor.