Table 1.

Sources, bioactives and underlying neuroprotective mechanisms of saponins.

S. no	Botanical Name	Compounds	Disease/Model	Neuroprotective Mechanism	Ref.
1	Gynostemma pentaphyllum	Gypenoside TN-2	Learning deficit	Brain-derived neurotrophic factor (BDNF) and, cAMP-response element binding protein (CREB)	[104]
2	Liriope platyphylla	Spicatoside A	AD	Nerve growth factor (NGF), extracellular signal-regulated kinase (ERK), PI3-kinase/serine/threonine kinase (AKT), Cell surface transmembrane receptor tyrosine kinase (TrkA) receptor activation, neural networks reconstruction	[105]
3	Anemarrhena asphodeloides	Timosaponin AIII	AD	Acetylcholinesterase (AChE) Inhibition	[106]
4	Xanthoceras sorbifolia	Xanthoceraside	AD	Acetylcholinesterase (AChE) inhibition, antioxidant	[107]
5	Polygala tenuifolia	Onjisaponin F	AD	Nerve growth factor (NGF), Choline Acetyltransferase (ChAT)	[108]
6	Kalopanax pictus	Kalopanaxsaponins A	AD	Acetylcholinesterase (AChE) inhibition, cAMP-response element binding protein (p-CREB)	[109]
7	K. pictus	Kalopanaxsaponins B	AD	Acetylcholinesterase (AChE) inhibition, cAMP-response element, binding protein (p-CREB)	[109]
8	Astragalus membranaceus	Astragaloside IV	PD, Stroke	Antioxidant, tumor interleukin-1β (IL-1β), necrosis factor α (TNFα), Nuclear factor kappa B (NF-κB), Ca2+ influx, regeneration of the neural network	[74]
9	Dipsacus asper	Akebia saponin D	AD	mitogen-activated protein kinase (MAPK) anti- apoptosis	[99]
10	Panax ginseng	Ginsenoside Rb1	AD, Stroke, HD	Antioxidant, Interleukin 6 (IL-6), necrosis factor α (TNF-α), anti-apoptosis, Ca2+ influx, Nerve growth factor (NGF), Glial Cell-Line Derived Neurotrophic Factor (GDNF), Brain-derived neurotrophic factor (BDNF), tau phosphorylation, NF-κB, PKA, Gβ1/PI3K/Akt, Ho-1, neurite outgrowth enhancing, TNF-α, NF-Κb	[74]
11	P. ginseng	Ginsenoside Rg1	PD, AD, Stroke	Antioxidant, Tumor necrosis factor α (TNF-α), NO, BDNF, GDNF, IGF-IR, NGF, Nuclear factor kappa B (NF-κB), PKA, JNK, ER, AChE, signaling pathway, neural networks reconstruction	[74]
12	P. ginseng	Ginsenoside Rg3	AD	Antioxidant, Tumor necrosis factor α (TNF-α), promote Aβ intake, iNOS, NMDA, interleukin-1β (IL-1β), AP-1, MSRA, PKA,	[74]
13	P. ginseng	Ginsenoside Rh2	AD	Tumor necrosis factor α (TNF-α), NMDA, AP-1, JNK-AP-1, PKA	[110]
14	P. ginseng	Ginsenoside compound K	AD	Nuclear factor kappa B (NF-κB), Tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), GABA, iNOS, Intercellular adhesion molecule-1 (ICAM-1), JNK/activator protein-1 (AP-1)-signaling pathway (JNK-AP-1),	[111]
15	P. ginseng	Ginsenoside Re	AD	Inhibit BACE1 via activation of PPARγ, and reduce the generation of Aβ1–40 and Aβ1–42	[112]
16	P. ginseng	Ginsenoside Rd	Stroke	Antioxidant, iNOS, cyclooxigenase-2 (COX-2), prostaglandins E2 (PGE2), Ca2+ influx, tau phosphorylation	[113,114]
17	P. ginseng	Ginsenoside Rg2	Stroke	Anti-apoptosis	[115,116]
18	P. ginseng	Ginsenoside Rh3	Microglia cells	iNOS, TNF-α, IL-1β	[117]
19	L. macranthoides	Akebiasaponin D	AD	antagonizes Aβ25-35-induced cytotoxicity in PC 12 cells	[118]
20	Panax notoginseng	Notoginsenoside R1	Neuroprotection	NMDA, Bcl-2/Bax, Ca2+ influx	[119]
21	P. notoginseng	Notoginsenoside R4	Neurite growth	Neural networks reconstruction	[120]
22	P. notoginseng	Notoginsenoside Fa	Neurite growth	Neural networks reconstruction	[120]
23	Platycodon grandiflorum	Platycodin D	Stroke	NF-κB, COX-2	[121]
24	P. grandiflorum	2″-o-Acetyl-polygalacin D2	Stroke	NF-κB, COX-2	[121]
25	White ginseng	Extract	AD	AChE/BChE	[122]
26	Red ginseng	Extract	AD	AChE/BChE	[122]
27	Black ginseng	Extract	AD	AChE/BChE, antioxidant	[122]
28	P. ginseng	Ginsenoside Rb3	Neurite growth	Antioxidant, GABA receptor, neurite outgrowth enhancing	[123]
29	P. ginseng	Ginsenoside Rc	HD	Ca2+ signaling pathway	[124]
30	P. ginseng	Ginsenoside Rd	Stroke	Antioxidant, iNOS, COX-2, PGE2, Ca2+ influx, tau phosphorylation	[113,114]
31	Asparagus racemosus	Sarsasapogenin	AD	Inhibits AChE/BChE, MAO-B, Inhibits Aβ42) fibrillization	[76]
32	Green Tea	theasaponin E1	AD	Inhibits tau hyperphosphorylation, declined Aβ levels, reduce inflammation	[77]
33	Panax notoginseng	Notoginsenoside R1	Neuronal cells	B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax), N-methyl-D-aspartate (NMDA) receptors, Ca2+ influx	[119]
34	C. asiatica	Asiaticoside	PD	Modulation of B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax), free radicals, dopamine balance	[125]
35	Astragalus membranaceus	Astragaloside IV	PD, Stroke,	Suppression of free radicals, TNF-α, NF-κB, IL-1β, Ca2+ influx, Improvement in regeneration of the neural network	[74]