Table 1.

Phenolic acids and related characteristics.

Phenolic Acids	Basic Description	Disease Models	Mode of Action	Ref.	Chemical Structure
Caffeic acid	Organic compound classified as a hydroxycinnamic acid. It consists of both phenolic and acrylic functional groups. Since it represents an intermediate in the biosynthesis of lignin (one of the principal components of woody plant biomass and its residues), caffeic acid can be found in all plants.	Mice treated with LPS	▪Attenuated sickness behavior ▪Decreased oxidative stress ▪Decreased inflammation	[18]
		Human α-syn aggregation	▪Counteracted aggregation	[21]
		Mouse model of epilepsy	▪Decreased oxidative stress and DNA damage	[22]
		Mouse model of acute seizure (diazepam and aspilocarpine-induced)	▪Reduced the latency to sleep ▪Reduced genotoxic damage	[23]
		Rat model of hyperinsulinemia	▪Modulated cerebral insulin signaling, Aβ accumulation, and synaptic plasticity ▪Ameliorated memory and learning impairments ▪Enhanced the antioxidant defense ▪Decreased the expression of p-tau in the hippocampus ▪Attenuated the expression of APP and β-site APP cleaving enzyme ▪Increased the expression of synaptic proteins	[24]
Caffeic acid phenethyl ester	Ester of caffeic acid and phenethyl alcohol.	Rats exposed to ionizing radiation	▪Reduced oxidative stress ▪Ameliorated the antioxidant defense	[25]
		Rats treated with IFOS	▪Decreased oxidative status and protein carbonyl levels	[28,29]
		Mouse model of HD (3-nitropropionic acid-induced)	▪Reduced striatal damage and the behavioral deficits ▪Reduced the activation of astrocyte and microglia	[31]
		BV-2 cells treated with LPS	▪Reduced oxidative stress ▪Attenuated LPS-dependent MAPK and Akt signaling pathways ▪Attenuated induction of HO-1 and EPO	[27]
		PC12 cells treated with (MPP+)	▪Increased the network of neuritis ▪Increased the expression of proteins responsible for axonal growth and synaptogenesis	[30]
		Rat cerebellar granule neurons treated with SNP or glutamate/glycine or H2O2	▪Decreased nitrosative stress, excitotoxicity, and oxidative stress	[38]
Chlorogenic acid	Ester of caffeic acid and (−)-quinic acid. It belongs to the polyphenol family of esters, including hydroxycinnamic acids (caffeic acid, ferulic acid and p-coumaric acid) with quinic acid.	Cortical mouse neurons treated with L-glutamic acid	▪Regulated the intracellular concentrations of Ca(2+)	[32]
		Microglia infected with herpes simplex virus	▪Decreased inflammation ▪Increased the survival rate ▪Prevented the increase in TLR2, TLR9, and Myd88	[33]
		Rats treated with H2O2	▪Reduced oxidative stress	[35]
		Mouse model of epilepsy (pilocarpine-induced)	▪Decreased lipid peroxidation ▪Decreased nitrosative stress ▪Reduced mRNA expression levels of NMDA receptors and mGluR1/mGluR5	[36]
		PC12 cells treated with ethanol	▪Increased the cell viability and promoted the proliferation of damaged cells ▪Increased the distribution ratio of the cells at the G2/M and S phases ▪Enhanced mitochondrial transmembrane potential ▪Modulated apoptosis mediators	[37]
		Rat cerebellar granule neurons treated with SNP	▪Protected against NO effects	[38]
Ferulic acid	Natural phenylpropanoid found in Euphorbia hylonoma herbs. It is a substituted derivative of trans-cinnamic acid.	N/A (untreated mice)	▪Decreased inflammation ▪Decreased oxidative stress ▪Increased serotonin and norepinephrine levels ▪Reduced depressive-like behavior ▪Inhibited the activity of MAO-A	[39]
		N/A (untreated mice)	▪Improved antidepressant-like effect ▪Increased antioxidant machinery in the cerebral cortex of mice	[40]
		Rat model of PD (ROT-induced)	▪Improved antidepressant-like effect ▪Increased antioxidant machinery in the cerebral cortex of mice	[41]
		Microglial cells treated with LPS	▪Decreased inflammation ▪Decreased oxidative stress	[42]
		Neuro-2a cells treated with H2O2	▪Antioxidant and anti-inflammatory activity ▪Up-regulated BDNF ▪Modulated apoptosis mediators	[43]
		Mouse model of chronic unpredictable mild stress	▪Up-regulated BDNF, PSD95, and synapsin I levels	[44]
		PC12 cells treated with LPS	▪Decreased inflammation ▪Attenuated the up-regulation of phosphodiesterase 4 activity ▪Decreased the up-regulation of the PDE4B mRNA ▪Reverted the down-regulation of CREB and pCREB	[45]
		Rat model of focal cerebral ischemic injury	▪Down-regulated MEK/ERK/p90RSK signaling pathway	[46]
		Hypoxia-stressed PC12 cells	▪Increased cell viability ▪Prevented membrane damage ▪Decreased oxidative stress ▪Decreased intracellular free Ca(2+) levels, lipid peroxidation, and PGE2 production ▪Reduced p-p38 MAPK ▪Modulated apoptosis mediators	[47]
Gallic acid	Phenolic acid classified as trihydroxybenzoic acid. It is found in gallnuts, sumac, witch hazel, tea leaves, oak bark, and in several other plants.	Mice, Neuro-2A, and primary microglial cells treated with Aβ	▪Counteracted cognitive dysfunction and down-regulated the levels of NF-κB acetylation in mice ▪Increased Neuro-2A cells viability ▪Decreased inflammation in microglia	[48]
		Rat model of TBI	▪Prevented memory deficits and synaptic impairment ▪Decreased inflammation	[49]
		Transgenic mice model of AD (APP/PS1)	▪Rescued learning and memory deficits	[50]
		Transgenic mice model of AD (APP/PS1)	▪Improved cognition ▪Counteracted synaptic impairment ▪Reduced Aβ aggregation	[53]
		Rat model of TBI	▪Improved memory and LTP impairment ▪Decreased lipid peroxidation ▪Decreased inflammation	[54]
		Mouse model of diabetes (STZ-induced)	▪Improved oxidative status	[55]
		Rats treated with cyclophosphamide	▪Decreased oxidative stress ▪Enhanced the antioxidant defense system	[56]
		Rats treated with sodium arsenite	▪Improved cognition ▪Decreased oxidative stress ▪Enhanced the antioxidant defense system	[57]
		Rat model of AD (AlCl3-induced)	▪Ameliorated hippocampal neurodegeneration and cognitive impairment ▪Decreased oxidative stress ▪Rescued the antioxidant defense system ▪Restored neurotransmitter levels	[58]
Rosmarinic acid	A polyphenol constituent of many culinary herbs such as rosemary, mint, and basil. From the chemical point of view, it represents a caffeic acid ester, with tyrosine giving another phenolic ring via dihydroxyphenyl-lactic acid.	Kindling mouse model (PTZ-induced)	▪Reduced the levels of free radicals and DNA damage ▪Increased the latency ▪Decreased the percentage of seizure incidents	[22]
		Kindling mouse model (PTZ and pilocarpine-induced)	▪Improved the latency to first seizures ▪Reduced the latency to sleep in the diazepam-induced sleeping time test ▪Decreased pilocarpine-induced genotoxic damage	[23]
		Rats exposed to noise	▪Attenuated hearing loss and hair cell damage ▪Reduced oxidative stress and lipid peroxidation ▪Enhanced the antioxidant machinery	[59]
		C6 glial cells treated with H2O2	▪Reduced oxidative stress and lipid peroxidation ▪Increased cell viability	[60,61]
		Rat model of SCI	▪Enhanced the antioxidant status ▪Decreased oxidative stress ▪Decreased inflammation	[62]
		Mouse model of a chronic restraint stress	▪Decreased p-tau and insoluble p-tau formation ▪Reverted the abnormal changes of chaperones and Pin1	[63]
		Rat organotypic hippocampal slice cultures treated with scopolamine	▪Enhanced LTP ▪Enhanced BDNF and GluR-2 protein expression ▪Enhanced cell survival rate	[64]
		Rat model of neuropathic pain	▪Decreased inflammation	[65]
Acetylsalicylic acid	A weakly acidic substance widely used as a medication to reduce pain, fever, as well as inflammatory processes. Chemically, it represents an acetyl derivative of salicylic acid.	Rats treated with tetrachlorodibenzo-p-dioxin	▪Decreased inflammation	[66]
		HIV-1 transgenic rat	▪Decreased inflammation ▪Decreased oxidative stress	[67]
		Rat model of ischemia	▪Improved learning and memory ▪Counteracted infarction volume and neural changes	[69]
		Mouse bone marrow-derived immature dendritic cells treated with LPS	▪Reduced the number of mouse bone marrow-derived immature dendritic cells expressing CD40 protein and MHCII	[70]
		BV-2 cells treated with LPS	▪Enhanced the expression of TfR1 and Fpn1 ▪Decreased the levels of ferritin contents ▪Decreased inflammation	[71]
Tannic acid	A specific form of tannins, a class of astringent, polyphenolic biomolecules, characterized by a very efficient metal chelating activity.	N/A (untreated rats)	▪Elevated the concentrations of NMDA receptors ▪Enhanced the antioxidant machinery ▪Decreased lipid peroxidation	[72]
		Rats treated with lead acetate	▪Decreased the neurochemical perturbations ▪Decreased oxidative damage ▪Restored antioxidant status	[73]
		Rat model of ischemia/reperfusion injury	▪Decreased lipid peroxidation ▪Enhanced the antioxidant machinery	[74]
		Rat model of MCAO	▪Counteracted behavioral deficits and improved neurological function ▪Decreased neurodegeneration ▪Reduced infarct size	[75]
Protocatechuic acid	A dihydroxybenzoic acid representing a major metabolite of antioxidant polyphenols found in green tea. It also possesses anti-inflammatory properties.	PC12 cells treated with H2O2	▪Modulated apoptotic mediators ▪Enhanced the antioxidant defense	[76]
		PC12 cells treated with MPP+	▪Suppressed mitochondrial dysfunction and apoptotic cell death ▪Decreased oxidative stress ▪Enhanced the antioxidant defense	[77]
		PC12 cells treated ROT	▪Ameliorated mitochondrial dysfunction ▪Suppressed apoptotic cell death	[78]
		Zebrafish, mice, and PC12 treated with 6-OHDA	▪Protocatechuic acid in combination with chrysin ▪Prevented neuronal loss in both zebrafish and mice ▪Increased cell viability, decreased oxidative stress, enhanced the antioxidant machinery, and decreased inflammation in PC12 cells	[79]
		BV2 cells treated with LPS	▪Modulated NF-κB and MAPKs signaling pathways ▪Decreased inflammation	[80]
		Rat model of diabetes (STZ-induced)	▪Exerted glycemic control ▪Attenuated brain mitochondrial dysfunction ▪Decreased oxidative stress	[81]
		Cerebellar granule neurons treated with H2O2 and BV2 cells treated with LPS	▪Decreased nitrosative stress and neurodegeneration in cerebellar granule neurons ▪Decreased inflammation in BV-2 cells	[82]
		Mice treated with sodium arsenate	▪Decreased lipid peroxidation and oxidative stress ▪Decreased inflammation ▪Attenuated histopathological changes	[83]
		PC12 cells treated with Aβ and α-Syn	▪Prevented cell death ▪Inhibited the aggregation of Aβ and α-Syn	[84]
p-coumaric acid	A hydroxycinnamic acid representing the hydroxy derivative of cinnamic acid. Among the three isomers of coumaric acid (o-, m-, and p-coumaric acid), p-coumaric acid represents the most abundant isomer that can found in nature.	Rat model of SNI	▪Reduced oxidative stress and axonal degeneration ▪Enhanced the antioxidant defense	[86]
		Rat model of SCI	▪Reduced ischemic fiber degeneration ▪Reduced Aβ protein accumulation ▪Decreased neuroinflammation	[87]
		Rat model of embolic cerebral ischemia	▪Modulated apoptotic mediators ▪Decreased lipid peroxidation	[88]
		Rat model of ischemia/reperfusion injury	▪Decreased lipid peroxidation ▪Enhanced the antioxidant defense ▪Decreased infarction size and hippocampal neuronal death	[89]
		Mice treated with LPS	▪Modulated apoptotic mediators ▪Decreased lipid peroxidation	[90]
		SH-SY5Y cells and primary rat cortical neurons treated with corticosterone	▪Enhanced the antioxidant defense ▪Increased CREB phosphorylation mediated by ERK1/2, Akt, and mTOR pathways	[91]
Sinapic acid	A small naturally occurring hydroxycinnamic acid belonging to the phenylpropanoid family. Due to its well-known ability to absorb laser radiation and donate protons to the analyte of interest, it is frequently used as a matrix in MALDI mass spectrometry experiments.	Mouse model of AD (Aβ-induced)	▪Rescued neuronal cell death at CA1 region level ▪Attenuated oxidative and nitrosative stress ▪Attenuated memory impairment ▪Attenuated glial cell activation	[93]
		Rat model of early PD (6-OHDA-induced)	▪Improved turning behavior ▪Counteracted the loss of dopaminergic neurons at substantia nigra pars compacta level ▪Lowered iron reactivity ▪Attenuated oxidative stress	[94]
		Rat model of global cerebral ischemia	▪Prevented neuronal damage ▪Reduced memory impairment	[95]
		Mice treated with kainic acid	▪Prevented neuronal damage ▪Reduced reactive gliosis ▪Reduced oxidative and nitrosative stress ▪Enhanced memory impairments	[96]
Ellagic acid	An organic heterotetracyclic compound found in different fruits and vegetables. From the chemical point of view, it represents the dilactone of hexahydroxydiphenic acid.	Rat model of sporadic AD (STZ-induced)	▪Reduced oxidative stress ▪Reduced inflammation ▪Reduced AchE and Aβ plaque levels ▪Improved synaptic connectivity ▪Normalized sporadic AD-associated abnormal behavioral representations	[97]
		Rat models of scopolamine- and diazepam-induced cognitive impairments	▪Prevented scopolamine- and diazepam-induced cognitive impairments	[98]
		Rat model of nerve injury (photothrombosis-induced) and OGD/R model in neural stem cells	▪Improved the rats’ nerve-related abilities, remedied infarct volumes and morphological changes in the brain, and enhanced the content of nestin protein in the brain semidarkness zone ▪Improved cell proliferation and neurorestoration through the activation of the Wnt/β-catenin signaling pathway	[99]
		Rat model of PD (6-OHDA-induced)	▪Restored the locomotion ▪Decreased inflammation in striatum and hippocampus	[100]
		Rat model of neonatal hypoxic-ischemic brain injury	▪Reduced infarct size, volume and tissue loss ▪Decreased neurodegeneration and inflammation ▪Down-regulated MAPK proteins ▪Modulated apoptotic mediators	[101]
Salicylic acid	A plant hormone representing a precursor to and a metabolite of acetylsalicylic acid (commonly known as aspirin).	Mice treated with METH	▪Decreased oxidative stress ▪Reverted mitochondrial dysfunction and ameliorated complex-I activity ▪Decreased neurotoxicity ▪Blocked behavioral changes related to movement abnormalities	[102]
		Primary cortex neurons treated with paclitaxel and cisplatin	▪Decreased cell death ▪Increased total antioxidant capacity ▪Decreased oxidative stress	[103]
Syringic acid	A dimethoxybenzene that is 3,5-dimethyl ether derivative of gallic acid having a role as a plant metabolite. It can be found in several plants such as Ardisia elliptica.	Rat model of brain ischemia injury	▪Decreased neuronal degeneration ▪Reduced oxidative stress ▪Increased total antioxidant capacity ▪Modulated apoptotic mediators	[109]
		Rat model of SCI	▪Decreased neuronal degeneration ▪Modulated apoptotic mediators ▪Ameliorated neurological deficit	[110]
		Hippocampal neurons subjected to OGD/R	▪Modulated apoptotic mediators ▪Decreased oxidative stress ▪Decreased intracellular levels Ca(2+) ▪Increased the levels of JNK phosphorylation, p38 phosphorylated expression ▪Increased cell viability ▪Rescued mitochondrial membrane potential and antioxidant defense	[111]
		Rat model of diabetes (STZ-induced)	▪Up-regulated the key regulators of energy metabolism, oxidative phosphorylation, and mitochondrial biogenesis ▪Attenuated lipid peroxidation ▪Reduced inflammation and demyelination in sciatic nerves ▪Improved learning, memory, and movement deficiency	[112]
		Rats treated with deltamethrin	▪Increased the dopamine levels ▪Ameliorated behavioral tests related to short-term and recognition memory	[113]
		Rat model of AD (AlCl3-induced)	▪Decreased oxidative stress ▪Decrease inflammation ▪Ameliorated neurobehavioral impairments	[114]
		Retinal ganglion cells treated with H2O2	▪Inhibited cell injury ▪Decreased oxidative stress and lipid peroxidation ▪Modulated apoptotic mediators ▪Activated PI3K/Akt signaling pathway	[115]
Cinnamic aldehyde	A phenylpropanoid synthesized by the shikimate pathway giving to cinnamon its characteristic flavor and odor. It can be found in the bark of cinnamon trees as well as other species of the genus Cinnamomum.	Mouse model of PD (MPTP-induced) and BE(2)-M17 cells treated with MPTP	▪Inhibited autophagy and prevented the selective dopaminergic neuronal death in the substantia nigra ▪Decreased autophagy and recovered MPP+-induced cell death in BE(2)-M17 cells	[117]
		Mouse model of permanent cerebral ischemia	▪Reduced neurological deficit scores, brain edema, and infarct volume ▪Decreased inflammation ▪Reduced the infiltration of leukocytes into the ischaemic brain	[118]
		Rabbit model of early brain injury (subarachnoid hemorrhage-induced)	▪Attenuated cerebral vasospasm ▪Increased the cross-sectional areas of the basilar artery and reduced the arterial wall thickness ▪Lowered hippocampal degeneration scores	[119]
		SH-SY5Y cells treated with Aβ	▪Reverted cell toxicity ▪Suppressed the activation of GSK-3β	[120]
		PC-12 cells treated with METH	▪Attenuated cell viability loss ▪Decreased oxidative stress ▪Restored the antioxidant defense ▪Modulated apoptotic mediators	[121]
		Aged rats treated with METH	▪Attenuated aging-induced memory impairment ▪Decreased oxidative stress ▪Decreased inflammation ▪Modulated apoptotic mediators	[122]
		Rat model TBI	▪Decreased neutrophil recruitment ▪Decreased oxidative stress ▪Reduced histologic damage and acute hippocampal dysfunction	[123]
		Mice subjected to acute or chronic stress	▪Decreased anxiety-related behavior in mice	[124]