Table 1.

Detailed information of the 14 studies.

Author (Year)	Animal Data	Quercetin Administration	Outcome Measure	Pharmacological Activities (Mechanisms)
Patil CS (2003) [5]	LPS-induced mice AD model (Swiss mice, male&female, 3 months old, 15–20 g and 16 months old, 35–40 g)	Dosage: 25, 50, and 100 mg/kg/day; Ad: i.p.; Duration: 7 days	Behavioral test (elevated plus maze, locomotor activity test, passive avoidance task, Rota-Rod test)	Prevented the cognitive impairment (oxidative stress↓)
Wang DM (2014) [6]	APPswe/PS1 dE9 transgenic AD mice (C57/BL) (male&female, 3 months old)	Dosage: 20 and 40 mg/kg/day; Ad: p.o.; Duration:16 weeks	Behavioral test (Novel Object Recognition Test, Morris Water Maze); Thioflavine S staining (Aβ deposition); WB (AMPK and p-AMPK levels)	Lessened cognitive deficits, reduced Aβ plaques and ameliorated mitochondrial dysfunction (AMPK activity↑)
Hayakawa M (2015) [7]	APP23 AD mice model (8 weeks old)	Dosage: 20 mg/day; Ad: p.o.; Duration: 4 weeks	Behavioral test (Contextual and auditory fear conditioning test); WB and ELISA (Aβ1-42, GADD34, ATF4, eIF2 a, etc.)	Improved memory (p-eIF2 a↓ and ATF4↓ through GADD34 induction)
Sabogal-Guáqueta AM (2015) [8]	Homozygous 3 xTg-AD mice (male&female, 18-21 months old)	Dosage: 25 mg/kg/2 days; Ad: i.p.; Duration: 3 months	Behavioral test (Elevated plus maze, Morris Water Maze); Immunohistochemistry (NeuN, βA, AT8, GFAP and Iba-1); WB (AT8, tau 5 and PHF-1 levels); ELISA (CTFα, CTFβ and βA1-40,42)	Reversed histological hallmarks of AD and protected cognitive and emotional function
Zhang X (2016) [9]	5XFAD transgenic mice (male&female, 6–8 weeks old)	Dosage: 500 mg/kg/day; Ad: p.o.; Duration: 10 days	Immunohistochemistry for Aβ; WB and qRT-PCR for apoE; ELISA (Aβ40 and Aβ42)	Increased brain apoE and reduced insoluble Aβ levels (inhibited apoE degradation)
Sun D (2016) [10]	APP/PS1 transgenic AD mice	Dosage: 10, 20 and 30 mg/kg (PLGA@QT NPs); Ad: i.v.; Duration: 30 days	Behavioral test (Morris Water Maze, Novel Object Recognition Test)	PLGA-functionalized quercetin (PLGA@QT) NPs ameliorated cognition and memory impairments
Moreno LCGEI (2017) [11]	SAMP1&SAMP8 mice (Male, 5 months old, 28–30 g)	Dosage: 25 mg/kg/day (Q) and 25 mg/kg/2 days (NPQ); Ad: p.o.; Duration: 2 months	Behavioral test (Morris Water Maze, Open field test, Rotarod test, Marble burying test); WB (GFAP, CD11)	Nanoencapsulaed quercetin (NPQ) improved the cognition and memory impairments (GFAP↓)
Vargas-Restrepo F (2018) [12]	Homozygous 3xTg-AD mice (male&female, 18–21 months old)	Dosage: 25 mg/Kg/48 h; Ad: i.p.; Duration: 3 months	Immunofluorescence (Iba-1 and βA); immunohistochemistry (GFAP, iNOS and COX-2)	Anti-inflammatory effect in CA1 hippocampal region
Khan A (2018) [13]	LPS-induced mice AD model (male, 8 weeks old, 25–30 g)	Dosage: 30 mg/kg/day; Ad: i.p.; Duration: 2 weeks	Behavioral test (Morris Water Maze, Y-maze); WB (GFAP, Iba-1, TLR4/NFKB, TNF-α, Caspase-3, etc.); Immunofluorescence (GFAP, Iba-1, p-NFKB, IL-1β, Caspase-3, etc.); Nissl staining	Reduced gliosis, prevented neuroinflammation in cortex and hippocampus, rescued the mitochondrial apoptotic pathway and neuronal degeneration (cyto. C↓, caspase-3↓ and PARP-1↓)
Rishitha N (2018) [14]	PTZ-induced Zebrafish AD model (adult male, <8 months old, 1.0–1.2 g)	Dosage: 5 and 10 mg/kg (Q and SLN-Q); Ad: i.p.; Duration: single	Light and dark chamber test; Partition preference test; Three horizontal compartment test; Spectroscopic method (GSH, TBARS, AChE levels)	Solid lipid nanoparticle of quercetin (SLN-Q) attenuated neurocognitive impairments along with amelioration of oxidative biomarker changes
Lu Y (2018) [15]	APP/PS1 transgenic AD mice (13 months old)	Dosage: 2 mg/g diet; Ad: p.o.; Duration: 9 or 13 months	Behavioral test (Morris Water Maze); Immunostaining (GFAP, 6E10); WB (APP, CTFβ, GFAP, etc); RT-qPCR (BACE1, PS1, Hevin, SPARC, Smad2, STAT3)	Ameliorated cognitive dysfunction only during early-middle stage of AD (astrogliosis↓, Aβ↓)
Karimipour M (2019) [16]	Aβ-injection rats AD model (Adult male Wistar rats, 350–400 g)	Dosage: 40 mg/kg/day; Ad: p.o.; Duration: 1 month	Morris water maze behavioral test; Immunohistochemistry (BrdU, DCX); Immunostaining (BrdU/NeuN double positive cells); RT-qPCR (BDN, NGF, CREB and ERG-1)	Increased proliferating neural stem/progenitor cells, enhanced adult neurogenesis (BDNF, NGF, CREB and EGR-1 genes expression↑)
Paula PC (2019) [17]	Homozygous 3xTg-AD mice (male&female, 6 months old)	Dosage: 100 mg/kg/48 h; Ad: p.o.; Duration: 12 months	Behavioral test (Elevated plus maze, Morris Water Maze); Immunohistochemistry (Aβ, AT-8)	Reduced β-amyloidosis, decreased tauopathy in hippocampus and amygdala, affected cognitive recovery
Li Y (2019) [18]	Aβ-injection rats AD model (male Sprague– Dawley rats, 220–280 g)	Dosage: 100 mg/kg/day; Ad: p.o.; Duration: 18 days	Morris water maze behavioral test; Estimation of oxidative stress (MDA level, SOD, CAT and GSH activity); Immunohistochemistry for Aβ; WB (Nrf2 and HO-1)	Promoted reversal of neuronal damage, Improved cognitive memory (Aβ1-42↓, antioxidant activity and Nrf2/HO-1 pathway↑)