Table 1.

Some neurochemical effects produced by flavonoid chrysin potentially involved in its anxiolytic- and antidepressant-like effects.

Activity	Chrysin Treatment	Effects	Reference
Antioxidant	20 mg/kg/30 days, p.o.	↓ TBARS, lipid hydroperoxides, conjugated dienes tissue, circulatory levels ↑ SOD, CAT, GPx, Gsr activity, GSH, GSTs, vitamin C and vitamin E levels in ethanol-induced toxicity in rats	[22]
	50 mg/kg/12 days, i.p.	↑ GHS levels and CAT and SOD activity in heart homogenate in male rats	[27]
	30 and 60 mg/kg/28 days, p.o.	↑ NO and GHS levels, GSHPx, CAT, and SOD activity in rat heart homogenate	[28]
	60 mg/kg/28 days, p.o	↑ 8-OHdG, TBARS levels ↓ GSH, CAT, NO levels	[29]
	1 and 10 mg/kg/60 days, p.o.	↑ SOD, CAT and GPx activity in PFC and HP of aged mice	[20]
	1.25, 2.5, and 5 µM/30 min exposure	↓ ROS formation in neuronal SH-SY5Y and microglial THP-1 cells in vitro	[30]
	10, 30, and 100 mg/kg/44 days, p.o.	Protects against aluminum-induced oxidative stress by restored LPO levels and SOD and CAT activity in cortex and HP of male Swiss mice	[30]
Anti-inflammatory	7.50, 4.75, and 120.90 µM, 18 h exposure	↓ NO, PGE2 and TNF-α biosynthesis in CLP-induced RAW 264.7 cells	[31]
	30 mg/kg/2 weeks, i.p.	↓ ALT and AST activity ↓ TNF-α and IL-1β levels ↑ IL-10 and adiponectin in high-fat feeding mice	[32]
	25 and 50 mg/kg/12 days, i.p.	↓ NF-κB, iNOS, COX-2, and TNF-α expression in heart homogenate of DOX-induced cardiotoxicity mice	[27]
	30 and 60 mg/kg/28 days, p.o.	↑ PPAR-γ and TGF-β expression ↓ NF-κBp65 and IKK-β expression and TNF-α level in heart homogenate of isoproterenol-induced myocardial injury rats	[28,29]
	5 and 20 mg/kg/28 days, p.o.	↓ TNF-α, IL-1β and IL-6 levels in PFC and HP of chronically stressed mice	[18]
	5 mg/kg/1 h before LP, i.p.	↓ AST and TNF-α serum levels in septic mice survival	[33]
	5 µM/24 h exposure	↓ iNOS, IL-1β, and TNF-α expression in microglial THP-1 cells exposed to LPS	[30]
GABAergic/BZD	3 µM, 60 min exposure	Acts as competitive ligand for central BZD site in bovine cerebral cortical membranes in vitro	[15]
	13 µM, 60 min exposure	Acts as competitive ligand for peripheral BZD binding site in rat kidneys membranes in vitro	[15]
	1 mg/kg, i.p.	Activates the GABAA/BZD receptor complex in male CF1 mice	[24]
	1 mg/kg, i.p.	Activates the GABAA/BZD receptor complex in male Sprague Dawley rats	[17]
	0.62 µM, 2 h exposure	Acts as competitive ligand for central BZD site in synaptosomal fractions of rat brain in vitro	[34]
	10 and 30 µM, 30 s exposure	Modulates the activity of Cl− ion channel in the GABAA receptor expressed in Xenopus oocytes in vitro	[35]
	2 mg/kg, i.p.	↓ Anxiety-like behavior by modulating Cl− ion channel in the GABAA receptor of cycling female rats	[36]
	2 mg/kg, i.p.	↓ Depression-like behavior by modulating GABA-binding site in the GABAA receptor of ovariectomized female rats	[37]
	0.5 µg/rat, i.h.	↓ Anxiety-like behavior by modulating GABAA/BZD receptor complex in the dorsal hippocampus of cycling female rats	[14]
Serotonergic	5 and 20 mg/kg, p.o.	↑ 5-HT levels and 5-HIAA/5-HT ratio in HP of chronic stressed mice	[18]
	20 mg/kg/28 days, p.o.	↑ 5-HT levels in PFC and HP in female mice with hypothyroidism	[12]
	50 mg/kg twice a day per 4 days, p.o.	↑ 5-HT levels in the striatum of the rat brain	[38]
	10 and 30 mg/kg/2 weeks, p.o.	↑ 5-HT spinal levels ↓ 5-HIAA/5-HT ratio in male mice with experimental neuropathy	[39]
	5 mg/kg/28 days, i.p.	↓ 5-HT1A receptor expression in the dorsal raphe ↑ 5-HT1A and 5-HT2A in the hippocampus of male rats	[13]
Dopaminergic	10 mg/kg/28 days, p.o	↑ DA striatal levels in mice	[19]
	50, 100 and 200 mg/kg/5 days, p.o.	↑ DA levels in striatum of mice treated with 1-methyl-1,2,3,6-tetrahidropidine	[40]
	20 mg/kg/28 days, p.o.	↑ DA levels in PFC and HP in a hypothyroidism model in female mice	[12]
Noradrenergic	50, 100 and 150 mg/kg, i.p.	↓ NE serum levels in rats with pain induced by formalin	[41]
	20 mg/kg/28 days, p.o.	No effects	[12]
Anti-apoptotic	25 and 50 mg/kg/12 days, i.p.	↓ Bax, caspase-3, and cytochrome c activity ↑ Bcl-2 expression in rat heart tissue extract	[27]
	30 and 60 mg/kg/28 days, p.o.	↑ Bcl-2 expression ↓ Bax and caspase-3 activity	[29]
	5 and 20 mg/kg/28 days, p.o.	↓ Caspase-3 and caspase-9 activity in HP and PFC of chronically stressed mice	[18]
	25, 50 and 100 mg/kg/3 days, p.o.	↓ Apoptotic index in cerebral cortex and HP of rats with traumatic brain injury	[42]
Neuroendocrine	5 and 20 mg/kg/28 days, p.o.	↓ Corticosterone plasma levels in chronically stressed mice	[11]
	5 and 20 mg/kg/28 days, p.o.	↓ CRH and ACTH in chronically stressed mice	[18]
	50, 100 and 150 mg/kg, i.p	↓ Corticosterone serum levels in rats with pain induced by formalin	[41]
Neurotrophic	5 and 20 mg/kg/28 days, p.o.	↑ BDNF and NGF levels in PFC and HP in chronically stressed mice	[11]
	1 and 10 mg/kg/60 days, p.o.	↑ BDNF levels in HP and PFC in aged mice	[20]
	10 mg/kg/28 days, p.o.	↑ BDNF and NGF levels in striatum in a Parkinson’s disease model in mice	[19]
	20 mg/kg/28 days, p.o.	↑ BDNF and NGF in HP and PFC in mice subjected to a hypothyroidism model	[43]

TBARS = thiobarbituric acid reactive substance; SOD = superoxide dismutase; CAT = catalase; GPx = glutathione peroxidase; Gsr = glutathione reductase; GSTs = glutathione-S-transferase; GSH = reduced glutathione; NO = nitric oxide; GSHPx = plasma glutathione peroxidase; 8-OHdG = 8-hydroxy-2′-deoxyguanosine; PFC = prefrontal cortex; HP = hippocampus; ROS = reactive oxygen species; LPO = lipid peroxidation; PGE₂ = prostaglandin E 2; TNF-α = tumor necrosis factor-α; CLP = cecal ligation and puncture procedure; ALT = alanine aminotransferase; AST = aspartate aminotransferase; IL-1β = interleukin 1 beta; IL-10 = interleukin 10; NF-κBp65 = nuclear transcription 116 factor kappa B heterodimer; iNOS = inducible nitric oxide synthase; COX- 2 = cyclooxygenase-2; DOX = doxorubicin; PPAR-γ = peroxisome proliferator-activated receptor-gamma; TGF-β = transforming growth factor-beta; IKK-β = inhibitor of nuclear factor kappa-B kinase subunit beta; IL-6 = interleukin-6; LPS = lipopolysaccharide; BZD = benzodiazepine; GABA = gamma-aminobutyric acid; 5-HT = 5-hydroxytriptamina, serotonin; 5-HIAA = 5-hydroxyindoleacetic; 5-HT_1A = serotonin 1A receptor; 5-HT_2A = serotonin 2A receptor; DA = dopamine; NE = noradrenaline; BAX = pro-apoptotic protein of the subfamily Bax; Bcl-2 = B-cell lymphoma-2; CRH = corticotropin-releasing hormone; ACTH = adrenocorticotropic hormone; BDNF = brain-derived neurotrophic factor; NGF = nerve growth factor; ↑ = increase; ↓ = decrease; p.o. = per oral route; i.p. = intraperitoneal injection; i.h. = intrahippocampal microinjection. (Table was prepared by the authors).