Table 3.

Summarizes the latest preclinical research findings on the effect of nano-formulated dietary small molecules against AD.

Dietary small molecules	Limitation	Nanocarrier	Nanocarrier size (nm)	Neurotoxin/duration	Drug concentration/duration	Mechanism of action	Reference
Chrysin	Poor oral bioavailability	Lipid-core nanocapsule	368–419	Aβ1–40 (3 μL for 1 day)	1 or 5 mg/kg bw for 14 days	Oral bioavailability ↑ Memory function ↑ NPSH, GSH, SOD, and CAT ↑ BDNF and IL-10 ↑ IL-1β and TNF-α ↓	[260]
Chrysin		Chitosan		Aβ1–40 (3 μL for 1 day)			[261]
Chrysin	Low bioaccessibility	Nanoemulsion	161	–	–	Bioaccessibility ↑ Cell viability ↑ Antioxidant activity ↑ AChE and BChE activity ↓	[262]
Chrysin	Poor pharmacokinetic profile	Solid lipid nanoparticles	240.0 ± 4.79	Aβ1–40 (3 μg for 1 day)	50 mg/kg bw for 21 days	Cognitive performance ↑ GSH, SOD, CAT, and GPx ↑ Vitamin-C ↑ TBARS and AChE ↓ Neuronal cell loss ↓ GFAP-positive astrocyte ↓	[263]
Naringenin	Low aqueous solubility and low bioavailability	Nanoemulsion	113.83 ± 3.35	Aβ1–40 (2 μM for 84 h)	0.125, 0.250, 0.5 μM for 24 h	Solubility ↑ Cell viability ↑ ROS production ↓ APP and BACE1 ↓ Aβ level, tau, and pT231 ↓	[264]
Luteolin	Low solubility and low permeability	Chitosan	412.8 ± 3.28	ICV-STZ (3 mg/kg for 1 day)	50 mg/kg bw for 21 days	Cognitive performance ↑ Spatial learning and memory ↑ GSH, Nrf2, and p-CREB ↑ Neuronal survival ↑ MDA, iNOS, and COX-2 ↓ MMP9, TNF-α, and NF-κB-p65 ↓ Aβ level and Tau ↓ Neuronal damage ↓ Aβ-plaques formation ↓ GFAP-positive astrocyte ↓	[265]
Luteolin	Low solubility and low permeability	Nanobilosomes	153.2 ± 0.98	ICV-STZ (3 mg/kg for 1 day)	50 mg/kg bw for 21 days	Cognitive performance ↑ Spatial learning and memory ↑ Neuronal survival ↑ MMP9 and TNF-α ↓ Aβ level and Tau ↓ Neuronal damage ↓ Aβ-plaques formation ↓ GFAP-positive astrocyte ↓ Iba-1-positive astrocyte ↓	[266]
Lycopene	Poor oral bioavailability	Microemulsion	<100	Aβ1–40 (10 μM for 1 day)	4 mg/kg bw for 21 days	Cognitive performance ↑ Spatial learning and memory ↑ Reelin, nestin, and Pax6 ↑ BrdU+, Dcx+, and BrdU+ ↑ Neun+, BrdU+, and Dcx+ ↑ p-GSK-3β and p-β-Catenin ↑	[267]
Lycopene		Microemulsion		Aβ1–40 (10 μM for 1 day)	4 mg/kg bw for 21 days	Memory function ↑ GSH, SOD, CAT, and GPx ↑ MDA levels ↓	[268]
FA	Poor aqueous solubility	Chitosan	185	ICV-STZ (3 mg/kg for 1 day)	80 mg/kg bw for 28 days	Solubility ↑ Oral bioavailability ↑ Memory function ↑ GSH and SOD content ↑ MDA, NO, and AChE activity ↓	[269]
EA	Low absorption and low permeability	Poly (lactic-co-glycolic acid)	277	AlCl3 (50 mg/kg for 28 days)	10 mg/kg bw for 14 days	Solubility ↑ Oral bioavailability ↑ Memory function ↑ Neuronal survival ↑ GSH and SOD content ↑ TBARS content ↓ Neuronal damage ↓ NFT and Aβ-plaque formation ↓	[270]
CA	Poor oral bioavailability and drug instability	Liposome	140	Aβ1–40 (10 μM for 1 h)	0.8 μM for 2 h	Oral bioavailability ↑ Stability ↑ Aβ aggregation ↓ Aβ fibril formation ↓	[271]
EGCG	Instability and low bioavailability	Poly (lactic-co-glycolic acid)	124.8 ± 5.2	Transgenic model	40 mg/kg bw for 90 days	Physicochemical stability ↑ Synaptic neurons ↑ Memory function ↑ Aβ-plaque and GFAP ↓	[272]
EGCG	Poor bioavailability and inefficient delivery	Nanolipids	<100	–	3.125–30 μM for 18 h and 100 mg/kg bw for 8 h	Oral bioavailability ↑ Stability ↑ α-secretase ↑	[273]