Table 2.

Summarizes the latest preclinical research findings on the effect of dietary small molecules bioactive compounds against AD.

Dietary small molecules	Bioactive constituents	BBB crossing ability	Type of study	Observed effects	Reference
Chrysin	4-oxo-2-phenyl-4H-chromene-5,7-diyl bis(piperidine-1-carboxylate)	Able	In vitro and in silico	Oral bioavailability ↑ Antioxidant activity ↑ AChE and BuChE ↓ Aβ aggregation ↓	[243]
7,8-DHF	7-O-β-d-glucosyl-8-hydroxyflavone, 7-hydroxy-8-O-β-d-glucosyl flavone, and 7,8-di-O-β-d-glucosylflavone	Not able	In vitro and in silico	APP and BACE inhibition ↓	[244]
Naringenin	Compound 3c and 5a	Able	In vitro and in silico	Cell viability ↑ Antioxidant activity ↑ AChE and BuChE ↓ Aβ aggregation ↓ Tau phosphorylation ↓ NO and TNF-α ↓	[245]
Naringenin	Compounds 5f and 7k	Able	In vitro, in vivo, and in silico	Cell viability ↑ Antioxidant activity ↑ AChE and BuChE ↓ Aβ aggregation ↓ NO and TNF-α ↓ Cognitive function ↑	[246]
Naringenin	5-hydroxy-2-(4-hydroxyphenyl)-4-oxochroman-7-yl piperidine-1-carboxylate	Able	In vitro and in silico	Oral bioavailability ↑ Antioxidant activity ↑ AChE and BuChE ↓ Aβ aggregation ↓	[247]
FA	Compounds 4g and 7f	Able	In vitro, in vivo, and in silico	Cell viability ↑ Antioxidant activity ↑ AChE and BuChE ↓ Aβ aggregation ↓ Cognitive function ↑	[248,249]
FA	TM-10	Able	In vitro, in vivo, and in silico	Cell viability ↑ Antioxidant activity ↑ Autophagy activation ↑ AChE and BuChE ↓ MAO-A and MAO-B ↓ Acute toxicity ↓ Aβ aggregation ↓ Cognitive function ↑	[250]
FA	Compounds 6j and 6k	Able	In vitro, in vivo, and in silico	Cell viability ↑ Antioxidant activity ↑ MDA, AChE, and BuChE ↓ BACE-1 activity ↓ Acute toxicity ↓ Cognitive function ↑ Oral bioavailability ↑	[251]
FA	Compounds FA-G1 and FA-DG1	Not able	In vitro and in vivo	Cell viability ↑ Aβ aggregation ↓ NO production ↓ iNOS and p-NF-κB-p65 ↓ Neuronal cell death ↓	[252,253]
CA	CAPE	Not able	In vitro and in vivo	NF200 and NeuN ↑ BDNF, nestin, and NeuN ↑ Neuromuscular activity ↑ Cognitive function ↑ PSD95, MAP-2, and GFAP ↓	[254]
CA	CAPE	Not able	In vitro and in vivo	Memory function ↑ Neuronal density ↑ Nrf2 and HO-1 ↑ GSK3β and p-GSK3β Oxidative stress ↓ GFAP and Iba-1 expression Caspase-9 expression ↓	[255]
CA	FA-97	Not able	In vitro and in vivo	Cell viability ↑ GSH and SOD activity ↑ Nrf2, HO-1, and NQO-1 ↑ Neuronal density ↑ Bcl2 expression ↑ LDH leakage ↓ MDA and ROS production ↓ Bax, caspase-9, and cyt-C ↓ Memory function ↑	[256]
Vanillin	Compounds 9e, 9h, 9 l, 9t and 9z	Not able	In vitro and in silico	Cell viability ↑ AChE, BChE, and DPPH ↓ Aβ aggregation ↓ Neuronal cell death ↓	[257]