Table 2.

Neuroprotective mechanisms of ginsenosides in AD treatments.

Ginsenoside	Subject	Dose	Duration	Targets	Actions	Reference
Rg1	MaleAPP/PS1 mice	i.p. injection (10 mg/kg)	30 days	BDNF, TrkB, BACE1, Aβ	Aβ deposition	[23,24]
	SK-N-SH neuroblastoma cells	50, 100 and 150 μM	30 min	IL-1β, tau, p38 MAPK	tau phosphorylation	[36]
	NG108-15 mouse glial cells	2, 4, 8, 16 and 32 μg/mL	24 h	TLR3, TLR4, TNF-α, IFN-β	Neuroinflammation	[53]
	PC-12 cells	20 μM	24 h	ROS, MDA, LDH, SOD	Anti-oxidation	[77]
	T2DM mice	orally administration (1, 5 and 10 mg/kg)	8 weeks	Ca2+, IP3, DAG, Aβ	Ca2+, IP3, DAG, Aβ	[84]
	SD rats	20 μmol/L	6 h	Ca2⁺, MAPK	Ca2⁺ homeostasis	[83]
	H4-APP cells	12.5, 25, and 50 μmol/L	24 h	Caspase-3	Anti-apoptosis	[88]
Rg2	PC12 cells	0.2 mmol/L	24 h	MDA, NO	Anti-oxidation	[78]
	PC12 cells	20 mg/mL	24 h	Caspase-3, Bcl2, BAX	Anti-apoptosis	[89]
Rg3	Rat primary microglial cells	25 μg/mL	8 h	Aβ, MSR-A	Neuroinflammation	[49]
	D-Gal induced rat	i.p. injection (20 mg/kg/day)	60 days	SOD, MDA	Anti-oxidation	[79]
	Murine macrophage cells	20 mM	16 h	NO, iNOS, NLRP3	Neuroinflammation	[59]
	primary hippocampal neurons	10 μM	2 days	Ca2⁺, NMDAR	Ca2⁺ homeostasis	[82]
Rg5	STZ-induced rats	i.c.v. injection (5, 10 and 20 mg/kg)	28 days	IGF-1, BDNF, Aβ	Aβ deposition	[16]
	STZ-induced rats	i.c.v. injection (5, 10 and 20 mg/kg)	28 days	AChE	Anticholinergic	[16]
Rb1	Rat primary cortical neurons	40 μM	24 h	p25, CDK5	tau phosphorylation	[44]
	Male SD rats	i.p. injection (5 mg/kg)	4 days	ACh	Anticholinergic	[65]
	Female ICR mice	orally administation (20 mg/kg/day)	4 months	GSK-3β, PP2A	tau phosphorylation	[47]
	PC-12 cells	1 mM	24 h	ROS, MDA, LDH, SOD	Anti-oxidation	[76]
	SD-rats	i.p. injection (12.5, 25, and 50 mg/kg)	14 days	Caspase-3, Bcl2	Anti-apoptosis	[90]
Rd	OVX rats	i.p. injection (10 mg/kg)	2 months	α-secretase, sAPPα, Aβ, MAPK/PI3K, ER	Aβ deposition	[25]
	APP/Tg mouse	i.p. injection (10 mg/kg)	6 months	IL-1β, IL-6, TNF-α, NF-κB, IL-10	Neuroinflammation	[54]
	Male SD rats APP transgenic mice	i.p. injection (30 mg/kg) i.p. injection (30 mg/kg)	7 days 6 months	GSK-3β, PP2A	tau phosphorylation	[46]
	N2a cells	5 μg/mL	48 h	ChAT, MAP2, p75, p21, Trka, VAChT, ACh	Anticholinergic	[66]
Re	N2a/APP695 cells	100 μM	24 h	BACE1, PPARγ, Aβ	Aβ deposition	[26]
	N2a cells	5 μg/mL	48 h	ChAT, MAP2, p75, p21, Trka, VAChT, ACh	Anticholinergic	[66]
	C57BL/6 mouse	orally administration (5, 10, 20 mg/kg)	4 weeks	ACh, AChE, JNK	Anticholinergic	[67]
	SH-SY5Y cells	25 uM	24 h	Cytochrome c, caspase 3/9, Bal 2/BAX, Nrf2	Anti-oxidation	[80]
Rh2	Tg2576 mice	i.p. injection (10 mg/kg)	8 weeks	sAPPα, CTFα/β, APP, Aβ	Aβ deposition	[27]
CK	db/db mice	orally administration (10 mg/kg)	10 weeks	NLRP3, caspase-1, IL-1β	Neuroinflammation	[60]