Table 2.

Inflammation-mediated cognition-improvement effect of ginseng in different animal models

No.	Ginseng component	Active dose and treatment duration	Diseases	Animal species	Model preparation	Molecular mechanisms	References
1	Ginsenoside Rg1	–	AD	–	–	Regulating NF-κB, NLRP1, TLR3, and TLR4 signaling pathways	Ding et al. (2022)
2	Ginsenoside Rf	20 mg/kg，(i.p.) for 2 weeks	AD	Male C57Bl/6 mice	Intraventricular injection of beta-amyloid peptide	IFN-γ, active caspase-1 expression ↓; IL-13 expression ↑; Aβ clearance speed ↑	Du et al. (2018)
3	KRG	20, 50, 100 mg/kg, (i.p.) for 14 days	PTSD	Male Sprague-Dawley rats	SPS	Regulating NF-κB and BDNF pathway	Lee et al. (2022)
4	Ginsenoside Rd	10, 20 or 40 mg/kg, (p.o.) for 28 days	Cognitive impairment	Male C57BL/6J mice	CRS for 35 days	Oxidative stress and inflammation ↓; hippocampal BDNF-mediated CREB signaling pathway ↑	Wang et al. (2020)
5	PNS	50, 100, 200 mg/kg/days for 3 days	HAND	Sprague-Dawley (SD) male rats	CCL2 injection (5 ng of 1 ng/μl)	Inflammation and apoptosis effects ↓	Zhou et al. (2020a, b
6	Ginsenoside Rg1	5, 10 mg/kg/daysfor 3 weeks	Chemobrain	Female C57BL/6J	Three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination at a 2-day interval	Modulating microglia-mediated cytokines and the related upstream mediators	Shi et al. (2019)
7	Shenmai or Shenfu	2 ml (i.v.) every 8 h for 3 days	POCD	Aged Sprague-Dawly rats	Nnderwent splenectomy under general anesthesia	Inflammatory factor (IL-6, TNF-α) ↓; COR, ALD, ACTH ↓	Zhang et al. (2018)
8	Ginsenoside Rg1	200 mg/kg (i.p.) for 30 days	Cognitive impairment	Wistar male rats	LPS (500 μg/kg, i.p.), single	Prevented LPS-induced decrease in ACh levels and increase of AChE activity; Reverted the decrease of α7-nAChR protein expression in the PFC and HP	Jin et al. (2017)
9	WGOS	40, 80 mg/kg (i.p.) for 30 days	Cognitive impairment	Male ICR mice	SCO-induced model (3 mg/kg)	Pretreatment scopolamine-induced hyperexpression of proinflammatory cytokines IL-1β and IL-6 mRNA ↓; astrocyte activation in the HP ↓	Xu et al. (2016)
10	Ginsenoside Rg5	5, 10, 20 mg/kg (p.o.) for 28 days	AD	Wistar rats	STZ-induced model (3 mg/kg, i.c.v.)	Inflammatory cytokines TNF-α and IL-1β ↓; AChE activity ↓; Aβ deposition ↓; IGF-1, BDNF ↑	Chu et al. (2014)
11	Panax ginseng	50, 100, 200 mg/kg (p.o.) for 2 weeks	Brain injury-induced cognitive dysfunction	Adult male Wistar rats	Traumatic brain injury model	Neuroinflammation (TNF-α and IL-6), AchE levels ↓; microglia activation ↓	Kumar et al. (2014)

Ach, Acetylcholine; AchE, Acetylcholinesterase; ACTH, Adrenocorticotropic hormone; AD, Alzheimer's disease; ALD, Aldosterone; Aβ, Amyloid-β peptides; BDNF, Brain-derived neurotrophic factor; CCL2, Chemokine CC motif ligand 2; COR, Cortisol; CREB, cAMP-response element binding; CRS, Chronic restraint stress; HAND, HIV-associated neurocognitive disorders; HP, hippocampus; IFN-γ, Interferon-gamma; IGF-1, Insulin-like growth factors-1; IL-13, Interleukin-13; IL-1β, Interleukin-1beta; IL-6, Interleukin-6; KRG, Korean Red Ginseng; LPS, lipopolysaccharide; NF-κB, Nuclear factor kappa-B; NLRP1, Nod-like receptor protein 1; PFC, Prefrontal cortex; PNS, Panax notoginseng saponins; POCD, Postoperative cognitive dysfunction; PTSD, Post-traumatic stress disorder; SCO, Scopolamine; SPS, Single prolonged stress; STZ, Streptozotocin; TLR3, Toll-like receptors 3; TLR4, Toll-like receptors 4; TNF-α, Tumor necrosis factor-alpha; WGOS, Water-soluble ginseng oligosaccharides.