Table 3.

In vitro and in vivo studies on polyphenols: mechanisms of action in Alzheimer’s disease prevention.

Polyphenol	Chemical Formula	Plant Origin	Experimental Model	Health Effects	Reference
Flavonoids
Epigallocatechin-3-gallate (EGCG)	C22H18O11	Camellia sinensis	SweAPP N2a cells transfected with the human APP gene. Cells were treated with various nanoparticle formulations and controls (25 µM: 3 µM) for 18 h.   Male Sprague Dawley rats, pre-cannulated and weighing between 200–250 g. Rats were administered 100 mg EGCG/kg BW via oral gavage, with blood samples collected over an 8 h period.	EGCG: Promotes non-amyloidogenic processing of APP by upregulating α-secretase, preventing brain Aβ plaque formation.	[221]
Epigallocatechin-3-gallate (EGCG) Luteolin Apigenin Naringenin Diosmin Flavone	EGCG: C22H18O11 Luteolin: C15H10O6 Apigenin: C15H10O5 Naringenin: C15H12O5 Diosmin: C28H32O15 Flavone: C15H10O2	EGCG: Camellia sinensis Luteolin: Many fruits, vegetables, and medicinal herbs Apigenin: Parsley, celery, and chamomile Naringenin: Citrus fruits Diosmin: Citrus fruits Flavone: Various plants including parsley and celery	N2a cells were stably transfected with the human APP-695 gene harboring the “Swedish” mutation (APPsw) Cells were treated with 1 µM EGCG for 48 h.   APP/PS-1 double-mutant transgenic mice. EGCG was administered to these mice at a concentration of 10 mg/mL in their drinking water, resulting in an approximate dose of 37.1 ± 1.6 mg/kg/day. The treatment was carried out over a period of 5.5 months	EGCG: Reduces Aβ levels and plaques. Provides cognitive benefits in AD transgenic mice. Restores mitochondrial respiratory rates, membrane potential, ROS production, and ATP levels in brain mitochondria.   Luteolin: Decreases ROS production. Restores mitochondrial membrane potential and ATP levels.   Apigenin, naringenin, diosmin, and flavone: Reduce oxidative stress. Restore mitochondrial function including respiratory rates, membrane potential, and ATP levels.	[222]
Epigallocatechin (EGC) Epicatechin-3-gallate (ECG)	EGC: C15H14O7 ECG: C22H18O11	Camellia sinensis	Neuro-2a cells. Cells were treated with Aβ40 and Cu2+/Zn2+-Aβ40 aggregates to induce neurotoxicity. EGC and ECG were used at a concentration of 20 μM, maintaining a ratio of [Aβ40]:[Cu2+/Zn2+]:[EGC/ECG] at 1:2:2 with an incubation time of 24 h.   APP/PS1 transgenic mice. Micewere administered ECG intravenously at a dose of 100 mg/kg during a study period of 2 months.	EGC and ECG: Reduce the aggregation of Aβ40 induced by Cu2+ and Zn2+. Inhibit the formation of β-sheet-rich Aβ40 aggregates. Alleviate the Cu2+- and Zn2+-induced neurotoxicity on N2a cells by reducing ROS production. ECG cross the BBB and reduce Aβ plaques in the brains of APP/PS1 mice, protecting neurons from damage.	[223]
Trilobatin (TLB)	C21H24O10	Lithocarpus polystachyus	HT22 hippocampal cells. The cells were treated with various concentrations of TLB, specifically 1, 5, and 10 μM. The incubation time for these treatments was 24 h.   C57BL/6J wild-type (WT) mice and 3xFAD transgenic AD mice. Animals were treated with TLB dissolved in saline and administered via gavage. The TLB concentrations used were 10 mg/kg and 20 mg/kg, administered once daily for 12 weeks.	TLB: Protects 3xFAD AD model mice against Aβ burden, neuroinflammation, tau hyperphosphorylation, synaptic degeneration, hippocampal neuronal loss, and memory impairment. Suppresses glial activation by inhibiting the TLR4-MYD88-NFκB pathway, leading to a reduction in inflammatory factors TNF-α, IL-1β, and IL-6. Ameliorates cognitive deficits. Reduces tau and Aβ pathology. Modulates spine plasticity. Protects against neuronal loss, and inhibited gliosis.	[224]
Trilobatin (TLB)	C21H24O10	Lithocarpus polystachyus	BV2 microglial cells BV2 cells were treated with Aβ25-35 to induce an AD model. TLB was administered at concentrations of 12.5, 25, and 50 μM. The treatment period for the experiments involving BV2 cells was not explicitly detailed but was sufficient to measure cell viability and cytotoxicity. Two animal models were used: APP/PS1 transgenic mice. Mice were administered TLB at doses of 4 and 8 mg/kg/day via intragastric (i.g.) administration for a period of 3 months. Rats subjected to intracerebroventricular (ICV) injection of Aβ25-35: These rats were subsequently administered TLB at doses of 2.5, 5, and 10 mg/kg/day via i.g. administration for 14 days.	TLB: Improves cognitive deficits in both animal models. Ameliorates neuroinflammation and oxidative stress by inhibiting the HMGB1/TLR4/NF-κB signaling pathway and activating the SIRT3/SOD2 pathway, which helps to restore redox homeostasis and suppress neuroinflammation.	[225]
Curcuminoid
Curcumin	C21H20O6	Curcuma longa	Differentiated SK-N-SH human neuroblastoma cells. Cells were treated with varying doses of NanoCurc™ at concentrations of 250 nM, 500 nM, 1 μM, 2.5 μM, and 5 μM. These cells were co-treated with 100 μM H2O2 simultaneously for 24 h.   Athymic mice Mice were administered NanoCurc™ intraperitoneally at a dose of 25 mg/kg twice daily for four weeks.	Curcumin: Reduces oxidative damage and amyloid pathology in AD models. Shows anti-inflammatory properties, inhibits pro-inflammatory transcription factors, and may disaggregate Aβ plaques, reducing neuroinflammation and protecting against AD progression.   NanoCurc™: Protects neuronally differentiated human SK-N-SH cells from ROS (H2O2) mediates insults and rescues cells previously insulted with H2O2. In vivo, decreases levels of H2O2, caspase 3, and caspase 7 activities in the brain, and increases glutathione concentrations.	[226]
Anthocyanins and Related Compounds
Delphinidin 3-galactoside (Del) and cyanidin 3-galactoside (Cya)	Del: C21H21O12 Cya: C21H21O11	Vaccinium myrtillus	Mouse neuroblastoma Neuro2a cells. The cells were exposed to Aβ samples incubated with or without VMA for either 24 or 48 h. Specifically, Aβ1–40 solutions were incubated at 37 °C for either 48 or 96 h, and Aβ1–42 solutions were incubated for either 24 or 48 h before being added to the cell cultures. The VMA concentrations used in the cell culture studies were typically prepared at a 2.5-fold molar ratio relative to the Aβ peptides. The incubation times varied depending on the specific assay but generally included intervals up to 96 h for Aβ1–40 and 48 h for Aβ1–42 Double-transgenic mice expressing human APP with the Swedish mutation (K670N/M671L) and human presenilin-2 proteins containing the N141I mutation. The DT mice were fed a diet supplemented with 1% VMA. The administration started at 60 days after birth and continued throughout the study period. Additionally, a lower concentration of 0.25% VMA was also tested in some groups of DT mice.	VMA Prevents cognitive degeneration in AD mice. However, this cognitive improvement was paradoxically associated with an increase in insoluble Aβ deposits in the brain, suggesting that VMA might promote the formation of non-toxic Aβ aggregates, diverting them from forming toxic species.	[227]
Myricetin, Quercetin, and Anthocyanin-rich extracts	Myricetin: C15H10O8 Quercetin: C15H10O7	The polyphenols were derived from blackcurrants and bilberries	Human SH-SY5Y neuroblastoma cells stably overexpressing the APP751 isoform. Myricetin: 2 and 20 μM Quercetin: 10 μM Anthocyanin-rich extracts: 8 and 31 /mLμg/mL. Incubation time: 24 h for normal growth conditions and assessments of viability and APP processing, 60 min for ROS measurement under menadione-induced stress conditions. Male APdE9 mice and age-matched wild-type littermates. Bilberry extract: 1.53 mg/g. Blackcurrant extract: 1.43 mg/g	Bilberry and blackcurrant anthocyanin-rich extracts: Decrease APP C-terminal fragments levels Alleviate spatial working memory deficits and hyperactivity in the APdE9 mouse model of AD. These findings suggest that dietary polyphenols from bilberries and blackcurrants might have potential benefits in modulating neurodegenerative processes associated with AD.	[228]
Mix of polyphenols
Grape Seed Polyphenol Extract (GSPE) Resveratrol	Resveratrol: C14H12O3	GSPE: Derived from grape seeds. Resveratrol: Found in grapes and wine.	Paired helical filaments (PHFs) isolated from AD brains.   PHFs were treated with 100 µM GSPE for varying incubation times, ranging from 5 s to 24 h, with a standard incubation time of 1 h generally used to ensure robust results.   TMHT mouse model of tauopathy. GSPE at concentrations ranging from 1 µM to 100 µM, and resveratrol at a concentration of 100 µM, was administered to the mice at a daily dose of 200 mg/kg BW for the duration of the animal experiment, which lasted four weeks.	GSPE: Disrupts and disintegrates the ultrastructure of native PHFs in AD brain. Inhibits tau aggregation and promotes dissociation from already assembled filaments. Significantly inhibits tau-mediated neuropathology in the TMHT mouse model. Suggested as a potential therapeutic agent for tau-mediated neurodegenerative conditions, like AD.   Resveratrol: Ineffective in altering the ultrastructure of PHFs as compared to GSPE. Not effective in inducing width expansion of filaments.	[229]
Punicalagin and ellagic acid, both components of pomegranate extract (POMx)	Punicalagin: C48H28O30 Ellagic Acid: C14H6O8	Punica granatum	HeLa/NFAT stable cell line. Polyphenol concentration: 0.1 mmol/L to 100 mmol/L for both punicalagin and ellagic acid. Incubation time: 30 min pre-treatment followed by 6 h of stimulation with TPA and ionomycin.   Male C57BL/6 APPswe/PS1dE9 transgenic mice. POMx at 6.25 mL/L in drinking water. Oral administration via drinking water for 3 months.	POMx: Improves behavioral performance. Reduces microgliosis. Decreases NFAT activity and lowers TNF-α concentrations in the brains of the APP/PS1 mice. These effects suggest that POMx has anti-inflammatory properties that may attenuate the progression of AD by reducing neuroinflammation and improving cognitive functions.	[230]
3-O-quercetin glucopyranoside Rutin 3-O-Quercetin rhamnopyranoside Chlorogenic acid	3-O-Quercetin Glucopyranoside (Isoquercetin): C21H20O12 Rutin (Quercetin-3-rutinoside): C27H30O16 Ursolic Acid: C30H48O3 Oleanolic Acid: C30H48O3 3-O-Quercetin Rhamnopyranoside (Quercitrin): C21H20O11 Chlorogenic Acid: C16H18O9 Scopoletin: C10H8O4	Bouvardia ternifolia (BtHA)	Human neuroblastoma cell line SH-SY5Y. Cells were treated with various concentrations of fibrillar Aβ (Ab1-42) peptide in the presence of BtHA or its specific fractions. The primary bioactive constituents of BtHA included 3-O-quercetin glucopyranoside (415 mg/g), rutin (229.9 mg/g), ursolic acid (54 mg/g), oleanolic acid (20.8 mg/g), 3-O-quercetin rhamnopyranoside (12.8 mg/g), chlorogenic acid (9.5 mg/g), and scopoletin (1.38 mg/g).   Male ICR-strain mice were employed to assess the anti-inflammatory activity using the TPA-induced ear edema assay. The BtHA extract and its fractions were administered topically at a dose of 6.5 mg per ear. The extract and fractions were applied 15 min after TPA treatment.	The study found that Bouvardia ternifolia extract exhibited significant neuroprotection against Aβ peptide, with anti-inflammatory, antioxidant, and anti-acetylcholinesterase effects. These effects are attributed to its content of polyphenols, coumarins, and triterpenes, suggesting potential as a therapeutic agent in the treatment of AD	[231]
Proanthocyanidins Hecogenin Ferulic acid Catechin Gallic acid Epicatechin Epicatechin gallate	Ferulic acid: C10H10O4 Catechin: C15H14O6 Gallic acid: C7H6O5 Epicatechin: C15H14O6	Fagopyrum dibotrys (FDE)	SH-SY5Y cells. Cells were treated with FDE at concentrations of 2.5 mg/mL, 5 mg/mL, and 10 mg/mL. The cells were incubated with these concentrations for 24 h to assess the neuroprotective effects against Aβ-induced toxicity.   APP/PS1 transgenic mice. Mice were administered a diet containing 0.65% FDE for a period of nine months. The amount of FDE consumed by the mice was approximately 0.103 mg/kg/day, ensuring consistent and long-term exposure to the extract.	FDE: Cleans Aβ deposits in the brain. Decreases Aβ burden in the plasma. Inhibits microhemorrhage. Reduces reactive microglia. Promotes Aβ fibrils disaggregation. Inhibits neurotoxicity induced by Aβ in SH-SY5Y cells.	[232]
Caffeic acid Trans-ferulic acid Isorhamnetin Irilin B	Caffeic Acid: C9H8O4 Trans-Ferulic Acid: C10H10O4 Acanthoside B: C34H44O20 Isorhamnetin: C16H12O7 Irilin B: (requires specific details for accurate formula)	Salicornia europaea L.	BV-2 microglial cells. The cells were pre-treated with SE-EE at concentrations of 20, 100, and 200 µg/mL for 1 h, followed by LPS stimulation (200 ng/mL) for either 6 or 24 h.   Male C57BL/6N mice, aged 8–9 weeks and weighing 24–27 g, were used. The mice were divided into five groups, receiving either 0.9% saline, scopolamine (2 mg/kg), SE-EE (50 or 100 mg/kg), or tacrine (10 mg/kg). SE-EE and tacrine were administered orally for 7 days prior to scopolamine injection. The total phenolic content in SE-EE was measured as 51.29 mg gallic acid equivalent per gram of sample, and the flavonoid content was 19.87 mg rutin equivalent per gram of sample.	SE-EE: Dose-dependently attenuates LPS-induced inflammation in BV-2 cell Improves cognitive function in scopolamine-induced amnesic mice by suppressing oxidative stress markers, regulating inflammatory cytokines and associated proteins expression, ameliorating p-CREB/BDNF levels, and promoting neurogenesis and neuron proliferation.	[233]
Caffeic acid Quercetin derivatives (Quercetin-exoside-rhamnoside, Quercetin-dirhamnoside) Kaempferol derivatives (Kaempferol-3-O-glucoside-7-O-rhamnoside, Kaempferol-3,7-O-dirhamnoside) Isorhamnetin-hexoside-rhamnoside Sinapic acid Luteolin Di-O-sinapoyl-β-glucose isomers	Caffeic acid: C9H8O4 Quercetin-rhamnoside-hexoside: C27H30O16 Kaempferol-3-O-glucoside-7-O-rhamnoside: C27H30O15 Quercetin-dirhamnoside: C27H30O15 Isorhamnetin-hexoside-rhamnoside: C28H32O16 Kaempferol-3,7-di-O-rhamnoside: C27H30O14 Sinapic acid: C11H12O5 Di-O-sinapoyl-β-glucose isomers: C28H32O14 Luteolin: C15H10O6	Arabidopsis thaliana	BV2 murine microglial cells. Cells were treated with 25 µM of aggregated Aβ25-35 peptide in the presence or absence of a polyphenolic extract from Arabidopsis thaliana. The extract was administered at a concentration of 20 µL/mL, derived from seedlings grown for seven days and cold-pressed to preserve the polyphenolic content. The incubation times for the treatments were set at 2 and 24 h.   Drosophila melanogaster flies expressing human Aβ1–42 were employed. The flies were fed a diet supplemented with 40 µL/mL of the Arabidopsis extract throughout their developmental period.	Arabidopsis thaliana: Has significant anti-inflammatory effects both in vitro and in vivo. In BV2 cells, the extract reduces the expression of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and increases the expression of anti-inflammatory cytokines (IL-4, IL-10, IL-13). These effects were observed after 24 h of treatment, indicating a robust anti-inflammatory response. The extract also activated the Nrf2-antioxidant response element signaling pathway, leading to upregulation of heme oxygenase-1 (HO-1) mRNA and increased NAD(P)H oxidoreductase 1 (NQO1) activity, which are indicators of enhanced cellular antioxidant defenses.   In the Drosophila model, the polyphenolic extract significantly improves the impaired climbing ability of the AD flies expressing human Aβ1–42, confirming its neuroprotective effects in vivo. This suggests that the extract could mitigate the neurotoxic effects of Aβ, potentially offering a protective strategy against neurodegenerative diseases, like AD.   These results highlight the potential of Arabidopsis thaliana polyphenolic extract as a therapeutic agent with anti-inflammatory and neuroprotective properties, warranting further investigation in more complex organisms to fully understand its impact on neuroinflammation and neurodegeneration.	[234]
Feruloylquinic acid p-Coumaroylquinic acid Rutin Quercetin-3(6″malonyl)-neohesperioside B-type procyanidin dimers Chlorogenic acids (CGAs) Flavan-3-ol glycosides Procyanidins	Feruloylquinic acid: C17H20O9 p-Coumaroylquinic acid: C16H18O8 Rutin: C27H30O16 Quercetin-3(6″malonyl)-neohesperioside: C29H34O17 Procyanidins: (C15H14O6)n Chlorogenic acid: C16H18O9	Humulus lupulus L.	Human neuroblastoma SH-SY5Y cells. Cells were treated with different concentrations of hop extracts or specific polyphenolic fractions. The polyphenol concentration used was 0.25 mg/mL for the total extract and concentrations varied for different fractions (e.g., 0.03 mg/mL for fraction B). The administration mode was direct incubation with the cell culture medium. For the cytotoxicity assay, SH-SY5Y cells were incubated with Aβ1–42 and hop extracts for 24 h.   Caenorhabditis elegans model (CL2006) expressing human Aβ3-42. The nematodes were treated with hop extracts at concentrations ranging from 10 to 250 /mLμg/mL. The administration mode was oral feeding, and the incubation/administration time was 120 h.	Humulus lupulus: Prevents Aβ1–42 aggregation and cytotoxicity. Exhibits antioxidant properties. Enhances autophagy, promoting the clearance of misfolded and aggregated proteins in SH-SY5Y cells. In vivo efficacy in reducing Aβ-induced toxicity in C. elegans models.	[235]
Polyphenol-rich fungi		Phellinus linteus, Ganoderma lucidum, and Inonotus obliquus	PC12 cells. These cells were treated with Zn2+ to induce Aβ aggregation. The cells were pretreated with different concentrations of the aqueous extract of mixed medicinal mushroom mycelia (MMMM) at 10 µg/mL (MMMM-L) and 100 µg/mL (MMMM-H) for 16 h before being exposed to 50 µM Zn2+ for 3 h.   5xAD transgenic mice. These mice were orally administered 30 mg/kg/day of MMMM for 8 weeks. Behavioral tests, including the Y-maze test (Y-MT) and the passive avoidance test (PAT), were conducted to assess memory function.	MMMM: In PC12 cells, MMMM treatment reduces Aβ aggregation, oxidative stress, and apoptosis while enhancing cell viability and antioxidant enzyme activity. In 5xFAD mice, MMMM treatment ameliorates memory impairments, reduced Aβ plaque accumulation, and decreased neuroinflammation in the hippocampus.	[236]
Hydroxycinnamic acids
Rosmarinic Acid (RA)	C18H16O8	Lamiaceae family, including rosemary and lemon balm.	BBB model using brain capillary endothelial cell monolayers. The experiments included controls, like caffeine and sodium fluorescein, to establish permeability benchmarks. For the permeability assay, the cells were incubated with RA, and permeability was measured over a period of 20 min at intervals.   5-month-old female Tg2576 mice (AD model) and 7–10-week-old female C57BL/6J mice. The Tg2576 mice were divided into control and RA-fed groups for a period of 10 months. The C57BL/6J mice were divided into a control group and a group fed with a diet containing 0.5% RA for 7 weeks. Tg2576 mice: RA was included in the diet at an unspecified concentration for 10 months. C57BL/6J mice: 0.5% RA was added to the diet and administered for 7 weeks. The administration was oral through dietary inclusion.	RA: Increases the concentration of monoamines (dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and levodopa) in the cerebral cortex of mice. Downregulates the expression of MAO B in the substantia nigra and ventral tegmental area, regions involved in dopamine synthesis. These changes were linked to a suppression of Aβ aggregation in the brains of the AD model mice, suggesting that RA has a potential therapeutic effect against AD by enhancing the dopamine-signaling pathway and inhibiting Aβ aggregation.	[237]
p-Coumaric acid	C9H8O3	Many fruits, vegetables, and cereals	PC12 neuronal cells. The concentration of pCA used was 50 µg/mL, and the cells were incubated for three days with Aβ42 (10 µM) at 37 °C.   Drosophila melanogaster (fruit fly). Various concentrations of pCA (50 µM, 100 µM, 500 µM, and 1000 µM) were administered through feeding. The administration was performed using a capillary feeder assay, and the effects were observed over a period corresponding to the lifespan of the flies, with specific attention paid to survival rate and locomotive ability.	p-Coumaric acid: Reduces Aβ42 fibrillation and decreases Aβ42-induced cell mortality in PC12 neuronal cells. In the Drosophila AD model, p-Coumaric acid partially reverses the rough eye phenotype, significantly lengthened lifespan, and enhanced mobility in a sex-dependent manner.	[238]
Tannins
Tannic Acid (TA)	C76H52O46	TA is a plant-derived hydrolyzable tannin polyphenol found in numerous herbaceous and woody plants.	SweAPP N2a cells. These cells were treated with varying concentrations of TA (1.563, 3.125, 6.25, 12.5, or 25 μM) for 12 h to evaluate the effects on Aβ production and APP metabolism.   Transgenic PSAPP mouse model. These mice were orally administered TA at a concentration of 30 mg/kg/day via gavage for 6 months. The study assessed cognitive function and AD-like pathology in these mice, including behavioral impairments, brain amyloid deposits, and neuroinflammation.	TA: Prevents behavioral impairments, such as hyperactivity, decreased object recognition, and defective spatial reference memory. reduces brain parenchymal and cerebral vascular amyloid deposits, and mitigates neuroinflammation. Decreases the production of various Aβ species, including oligomers. These effects were linked to the inhibition of BACE1 expression and activity, and a shift towards non-amyloidogenic APP processing pathways, suggesting that TA might serve as a potential prophylactic treatment for AD.	[239]
Xanthones
Alpha-mangostin	C24H26O6	Garcinia mangostana	BV-2 microglial cells, Chang liver cells, and bEnd.3 mouse brain endothelial cells. Cells were treated with α-mangostin (α-M) or its nanoparticle formulation (NP(α-M)). The concentrations used were 25, 50, and 100 ng/mL for BV-2 cells and 50, 500, and 1000 ng/mL for Chang liver cells. These cells were treated for 24 h, followed by incubation with 2 μg/mL Aβ 1-42 (Aβ1–42) in serum-free DMEM for an additional 24 h.   Male SAMP8 mice, female APP/PS1 transgenic mice, and Kun-Ming mice. Animals were administered intravenous injections of either α-M solution or NP(α-M) at a dosage of 1 mg/kg/day over a period of four weeks.	α-mangostin: Upregulates LDLR expression. Increases cellular uptake and degradation of Aβ1–42. Enhances brain clearance of Aβ1–42. Reduces Aβ deposition. Attenuates neuroinflammatory responses. Ameliorates neurologic changes. Reverses behavioral deficits in AD model mice.	[240]
Avenanthramides
Avenanthramide-C (Avn-C)	C17H15NO4	Avena sativa	Hippocampal slices prepared from wild-type (C57BL/6J) and AD transgenic mice (Tg2576 and 5xFAD). The slices were treated with different concentrations of Avn-C (specifically 50 µM) and exposed to 0.5 µM oligomeric Aβ42 to examine the effects on long-term potentiation (LTP). The slices were incubated in artificial cerebrospinal fluid (aCSF) perfused with a gas mixture of 95% O2 and 5% CO2 at room temperature. The treatment duration for Avn-C was 2 h, with a 0.5-h pretreatment period before the addition of Aβ42   Wild-type C57BL/6J mice, Tg2576, and 5xFAD transgenic mouse models of AD. Male mice aged 7–8 months for Tg2576 and 5–6 months for 5xFAD Avn-C was administered orally at a concentration of 6 mg/kg per day for a period of 2 weeks.	Avn-C: Improves memory and cognitive functions in the transgenic mouse models of AD. Reverses the impaired LTP in both ex vivo- and in vivo-treated AD mice hippocampus. Improves recognition and spatial memory. Reduces caspase-3 cleavage. Reverses neuroinflammation. Increases levels of phosphorylated glycogen synthase kinase-3β (pS9GSK-3β) and IL-10. These beneficial effects are mediated through the binding of Avn-C to α1A adrenergic receptors, stimulating AMPK.	[241]

Aβ: amyloid-beta; AD: Alzheimer’s disease; α-M: alpha-mangostin; AMPK: AMP-activated protein kinase; APP: amyloid precursor protein; ATP: adenosine triphosphate; Avn-C: avenanthramide-C; BBB: blood–brain barrier; BW: body weight; ECG: epicatechin-3-gallate; EGC: epigallocatechin; EGCG: epigallocatechin-3-gallate; FDE: Fagopyrum dibotrys extract; GSPE: grape seed polyphenol extract; HMGB1: high-mobility group box 1; HO-1: heme oxygenase-1; IL: interleukin; LTP: long-term potentiation; MAO B: Monoamine oxidase B; NanoCurc™: nanoparticle formulation of curcumin; NFκB: nuclear factor kappa-light-chain-enhancer of activated B cells; NQO1: NAD(P)H quinone dehydrogenase 1; Nrf2: nuclear factor erythroid 2-related factor 2; N2a: neuro-2a, a murine neuroblastoma cell line; PAT: passive avoidance test; PHFs: paired helical filaments; POMx: pomegranate extract; RA: rosmarinic acid; ROS: reactive oxygen species; SE-EE: Salicornia europaea ethanol extract; SIRT3: sirtuin 3; SK-N-SH: human neuroblastoma cell line; SweAPP: Swedish amyloid precursor protein; TA: tannic acid; TLB: trilobatin; TNF-α: tumor necrosis factor-alpha; TPA: 12-O-Tetradecanoylphorbol-13-acetate; VMA: Vaccinium myrtillus anthocyanins; WT: Wild-type; Y-MT: Y-maze test.