Table 2.

Effects of Different Components of Honey in Various Neurological Disorders.

Disease	Component	Effect	References
Alzheimer’s Disease	Quercetin	Improves mitochondrial activity	[89]
		Activates Nrf-2 signaling	[90]
		Deceases oxidative stress
		Reduces oxidative stress via PON2 activity	[91]
		Reduces neuroinflammation	[92,93]
		Decreases astrogliosis
		Prevents neurodegeneration
		Recovers cognitive disabilities
	Myricetin	Improves memory and cognitive function	[94]
		Prevents the formation of fibrils as well as oligomers of Aβ	[95]
		Anti-tau protein effect
		↓ Acetylcholinesterase	[96]
		↑ Acetylcholine
		Exhibits anti-inflammatory activity	[97,98]
		Inhibition of the NF-κB pathway and NLRP3 inflammasome
		Prevents the formation of fibrils as well as oligomers of Aβ	[99]
	Kaempferol	Decreases lipid peroxidation and senile plaque formation	[100]
		Protects from apoptotic damage
		Regulates concentrations of antioxidative enzymes	[101]
		↓ TNF-α and inhibits inflammation
		Exhibits anti-apoptotic activity	[102]
		Downregulates Bcl-2-associated X protein (Bax) and cleaved caspase-9
		Increases neuronal density in the hippocampus	[103]
		Downregulates inflammatory proteins	[104]
		Protects from oxidative damage	[105]
	Luteolin	Alleviates oxidative stress	[106]
		Scavenges free radicals
		Downregulates inflammatory and apoptotic proteins
		Improves memory deficits	[107]
		Maintains neuronal density
	Galangin	Diminishes autophagy	[108]
		Decreases levels of p-tau, β-secretase, and Aβ42
		↑ Acetylcholine	[109]
		Improves cognitive functions
	Caffeic acid	↓ Acetylcholinesterase	[110]
		↓ Inflammation
		↓ Oxidative stress
	Cinnamic acid	Attenuates the formation of amyloid plaques	[111]
		Activates PPARα
		Improves memory functions
Parkinson’s Disease	Quercetin	Protects from degeneration	[112]
		↑ Dopamine levels
		↑ Brain-Derived Neurotrophic Factor expression
		↑ Energy production of mitochondria
		Restores activities of antioxidant enzymes	[113]
		Repairs cognitive deficits
		↓ Endoplasmic reticulum stress	[114]
		↓ C/EBP homologous protein (CHOP)
		↑ Autophagy
		↑ Beclin-1 expression
	Myricetin	↓ Degeneration	[115]
		↑ Dopamine levels
		Inhibits inflammation	[116]
		Prevents the activation of microglia
		↓ Expression of inflammatory cytokines
	Chrysin	↑ Expression of a survival factor MEF2D	[117]
		Inhibits MAO-B
		Alleviates oxidative stress	[118]
		Prevents inflammation and dysfunction of Na+, K+-ATPase pump
		Ameliorates neuronal loss	[119]
		Improves memory
	Ellagic acid	Inhibits MAO activity	[120]
		Prevents the loss of neurons
		↓ Oxidative stress
		Modulates levels of antioxidant enzymes	[121]
		Protects from oxidative insult
		Diminishes apoptosis	[122]
		Inhibits MAO-B
		Modulates ERβ/Nrf2/HO-1 signaling cascade
	Cinnamic acid	Protects neurodegeneration	[123]
		Activates Peroxisome Proliferator Activating Receptor α (PPARα)
	Galangin	Inhibits microglial activation	[124]
		Suppresses inflammatory factors
		Activates PPAR-γ	[125,126,127]
		Inhibits inflammation
		Prevents apoptosis
		Protects from oxidative damage
	Apigenin	Exhibits antioxidative function	[128]
		Inhibits MAO
		Prevents apoptosis
		Inhibits caspase-3 activation
Huntington’s Disease	Quercetin	Improves motor functions	[129]
		Regulates peroxisome proliferator-activated receptor gamma, coactivator (PGC-1), or sirtuins (SIRT1)
		↑ Energy production of mitochondria
		Ameliorates behavioral malfunctions	[130]
		Exhibits anxiolytic effect
	Myricetin	Reduces aggregation of polyglutamine	[131]
		↓ Proteo toxicity	[132]
		Repairs behavioral changes
	Chrysin	Upregulates anti-apoptotic factor	[133]
		Downregulates pro-apoptotic factor
		Restores neurobehavioral functions	[134]
		↑ Serotonin
	Chlorogenic acid	Protects from genotoxicity	[135]
Amyotrophic Lateral Sclerosis	Quercetin	Inhibits aggregation of Cu-Zn superoxide dismutase (SOD)	[136,137]
	Kaempferol	Prevents cell death	[138,139]
		Reduces aggregation of superoxide dismutase 1 (SOD1)
		↑ AMPK phosphorylation
		Inhibits mTOR phosphorylation
		Boosts up autophagy
	Coumaric acid	Ameliorates oxidative stress and endoplasmic reticulum stress	[140]
		↑ Autophagy
	Gallic acid	↑ Levels of antioxidant enzymes	[141]
		↓ Lipid peroxidation
		Downregulates inflammatory cytokines such as TNF-α, IL-6, IL-β, and NF-κB
		Improves motor functions
		Prevents glutamate excitotoxicity	[142]
		Inhibits the formation of neurofibrillary tangles
		Improves motor skills
		↓ TDP-43 proteotoxicity	[143]
		Attenuates seizures
Epilepsy	Quercetin	Inhibits activation of microglial cells and inflammatory cytokines	[144]
		Attenuates neurodegeneration
		Inhibits expression of the gene for GABA receptors	[145]
		Reduces depression
		Restores tryptophan levels	[146]
		Exerts anticonvulsant effect
		Modulates Glycinergic and GABAergic ion channels	[147]
		Reduces behavioral signs of seizures
		↓ Neuronal loss	[148]
		↓ Astrocyte activation
	Myricetin	Ameliorates intensity of seizures	[149,150]
		Inhibits apoptosis
		Downregulates Bad, Bax, and cleaved caspase 3
		Upregulates Bcl-2 and Bcl-xL
		Normalizes glutamate/GABA
	Luteolin	Improves cognitive deficits	[151]
		↑ Expression of Brain-Derived Neurotrophic Factor (BDNF)
		Exhibits anticonvulsant effect	[152]
		↑ Activation of receptors for GABAA
		Reduces oxidative stress
		Improves cognition impairments	[153]
		Modulates CaM-CaMPK signaling pathway
		Attenuates seizures
	Chrysin	Modulates GABAA receptors	[154]
		Abrogates convulsion-induced oxidative damage
		↓ The severity of epileptic seizures	[155]
		↓ Apoptosis
		Boosts the expression of Nrf2, NQO-1, and HO-1
	Apigenin	Reduces neuronal loss	[156]
		↓ Release of cytochrome c from mitochondria
		Alleviates apoptosis
		Inhibits overexpression of hypochlorite (HClO)	[157,158]
		↓ Oxidative damage
		Averts cognitive impairments	[159]
		Exerts antidepressant and anti-anxiolytic effects
		↑ Expression of Brain-Derived Neurotrophic Factor (BDNF)
	Ferulic acid	Palliates depression	[160]
		↓ Levels of proinflammatory cytokines such as TNF-α and IL-1β
		Inhibits Cyclooxygenase 2 (COX2) activity
		Modulates corticosterone levels
		Ameliorates oxidative stress	[161]
		Upregulates neuroprotective Heat shock protein 70 (Hsp70) and neurotransmitters such as Serotonin (5-HT) and norepinephrine
		Diminishes oxidative stress	[162]
		Repairs cognitive deficits and seizure activity
		Improves memory functions and learning capacities	[163]
		Inhibits apoptotic process
		Scavenges free radicles
	Naringenin	↑ Antioxidant enzymes	[164]
		Restores neuronal morphology
		↓ Neurodegeneration
		Impedes occurrence of seizures	[165]
		↓ Granule cell disruption (GCD) in the hippocampus
		Ameliorates generation of proinflammatory cytokines
		Exerts anticonvulsant effect	[166]
		Agonist effect on GABAA receptors
		↓ Glutamate transmission
Schizophrenia	Quercetin	Scavenges free radicals	[167]
		↑ Levels of antioxidant enzymes
		Reduces depressive behaviors	[168]
		Improves behavioral impairments	[169]
		Boosts up antipsychotic therapy	[170]
Depression	Quercetin	↑ Levels of antioxidant enzymes	[171,172]
		↓ Decrease levels of inflammatory cytokines
		Accrues serotonin level
		Mitigates depressive behaviors	[173]
		Modulates levels of BDNF
	Myricetin	Recovers hopeless behaviors	[174,175]
		Regulates BDNF levels
		Exerts antioxidant effect
	Kaempferol	Exert anti-depressive effects	[176]
		↑ Levels of antioxidant enzymes
		Upregulates AKT/β-catenin cascade
	Chrysin	Upregulates nerve growth factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF)	[177]
		Normalizes Na+, K+-ATPase activity
		Employs anti-depressant effects	[178]
		Inhibits kynurenine pathway
		Elevates the levels of serotonin (5HT)
	Naringenin	Performs anti-depressive activity	[179]
		Restores antioxidant enzymes’ levels
		Modulates serotonin levels
		Downregulates inflammation mediators
		Inhibits acetylcholinesterase activity	[180]
		Mitigates oxidative damage
		Upregulates BDNF, Sonic Hedgehog (Shh) signaling, NKX2.2, and PAX6	[181]
	Coumaric acid	Improves behavioral hopelessness	[182]
		Lessens inflammation-associated alterations
		Enhances neurotrophic activity
	Ferulic acid	Abrogates depression-like behaviors	[183]
		Downregulates pro-inflammatory cytokines
		Downregulates factors associated with inflammation and apoptosis	[184]
		Mitigates depression