TABLE 1.
The in vivo studies on the antidepressant effects of quercetin.
| Animal | Experimental model | Modeling method | Usage | Dosage | Evaluation Method | Function | Refs |
|---|---|---|---|---|---|---|---|
| Mice | Balb/c mice | Aflatoxin B1 intervention | p.o | 30 mg/kg | FST, OFT, MWM, NOR | Quercetin reduced the immobility time in FST, increased the time spent in left in OFT, reduced the anxiety-like behaviors in EPM and MWM and increased the exploration time in NOR | Gugliandolo et al. (2020) |
| C57BL/6N mice | CSDS | Dietary intervention | 0.5, 2 g/kg | TST, SPT, OFT, EPM, social interaction test | Quercetin reduced the immobility time in TST and increased the time spent both in the left zone in OFT and in the open arm in EPM. | Zhang et al. (2020b) | |
| C57BL/6J mice | Estrogen receptor α missing | p.o | 100 mg/kg | TST, FST | Quercetin reduced the immobility time of mice both in TST and in FST. | Wang et al. (2021b) | |
| C57BL/6J mice | LPS intervention | i.p | 30, 60 mg/kg | TST, FST, neurons and microglia activities | Quercetin reduced the immobility time both in TST and in FST, suppressed the activation of microglia and alleviated the loss of DA neurons | Han et al. (2021) | |
| ICR mice | LPS intervention | i.p | 10 mg/kg | TST, FST, SPT, OFT | Quercetin reduced the immobility time in both TST and FST, reversing the anhedonia-like activities in SPT | Sun et al. (2021) | |
| KM mice | CUMS | p.o | 10, 20, 40 mg/kg | FST, SPT, OFT | Quercetin reduced the immobility time in FST and enhanced sucrose preference in SPT | Guan et al. (2021b) | |
| NMRI mice | mTBI | p.o | 50 mg/kg | OPT, EPM, zero maze, light-dark box, HPA axis activity | Quercetin reduced anxiety-like behaviors in behavioral tests, decreasing the levels of adrenocorticotropic hormones and corticosterone | Kosari-Nasab et al. (2019) | |
| Swiss mice | OB | p.o | 25 mg/kg | TST, FST, OFT, splash test | Quercetin reduced the immobility time in both TST and FST, reducing locomotor activities in OFT. | Holzmann et al. (2015) | |
| Swiss mice | GBH intervention | p.o | 30 mg/kg | FST, SPT, OFT, EPM | Quercetin demonstrated a partial improvement in the number of entries in EPM and reduced the immobility time in FST. | Bicca et al. (2021) | |
| Swiss albino mice | CRF antagonist intervention | p.o | 10, 20, 40 mg/kg | FST, social interaction test, locomotor activity | Quercetin reduced the immobility time in FST and increased their social interaction time in social interaction test | Bhutada et al. (2010) | |
| Swiss albino mice | CUMS | p.o | 25 mg/kg | TST, MFST, OFT | Quercetin reduced the immobility time of mice both in TST and in MFST, increasing field crossings and the time spent in left in OFT | Khan et al. (2019) | |
| Swiss albino mice | CUS | p.o | 30 mg/kg | MWM, NOR | Quercetin increased the number of platform crossings and the time spent in searching platform in the target quadrant in MWM, increasing discrimination between novel and familiar objects in NOR. | Mehta et al. (2017a) | |
| Swiss albino mice | CUS | p.o | 30 mg/kg | OFT, SPT, EPM, passive avoidance step-through task | Quercetin enhanced sucrose preference and exploration behaviors of mice | Mehta et al. (2017b) | |
| Swiss albino mice | 72 h of sleep deprivation | p.o | 25, 50 mg/kg | TST, OFT, NOR | Quercetin reduced the immobility time of mice in TST, increased number of lines crossed in OFT and increased the duration of exploration of the novel object in NOR. | Eduviere et al. (2021) | |
| Wistar albino mice | Immobilization stress | i.p | 20 mg/kg | FST, LDA, EPM, MWM, antioxidant enzyme activity | Quercetin reduced the immobility time in FST, improved the time spent in open arms in EPM, increased the time spent in the light box in LDA, decreased the time to reach the hidden platform in MWM and reduced the levels of MDA in their brains | Samad et al. (2018) | |
| Pigs | Guinea pigs | Lumateperone intervention | p.o | 50 mg/kg | FST, OFT | Quercetin reduced the immobility time in FST, causing a significant increase in crossing squares in OFT. | El-Haroun et al. (2021) |
| Rats | SD rats | CUMS | p.o | 10, 50 mg/kg | SPT | Quercetin reduced the depressive behaviors of animals in SPT. | Guan et al. (2021a) |
| SD rats | LPS intervention | p.o | 40 mg/kg | FST, SPT, OFT, MWM, Y maze | Quercetin reduced the immobility time in FST, improving sugar water preference index in SPT and new arm preference index in OFT. | Fang et al. (2019) | |
| SD rats (pregnant) | MS | Dietary intervention | 0.03% | FST, OFT, EPM | Quercetin reduced the immobility time in FST and increased the number of entries in the open arms in OFT. | Donoso et al. (2020) | |
| Wistar rats | ADR intervention | i.p | 60 mg/kg | FST, OFT, EPM | Quercetin reduced the immobility time in FST and the anxiety-like behaviors in both OFT and EPM. | Merzoug et al. (2014) | |
| Wistar rats | Alloxan induces diabetes | p.o | 100 mg/kg | FST, OFT, EPM, social interaction test | Quercetin increased the time spent in swimming and struggling in FST, increased the time spent in left and the total distance traveled in OFT, improved the time spent in open arms and the locomotive distance in EPM and enhanced the sociability in social interaction test | Toumi et al. (2019) | |
| Wistar rats | CUMS | p.o | 50 mg/kg | FST, SPT | Quercetin reduced the immobility time in FST, increased the sucrose consumption in SPT and inhibited the iNOS and MDA in animals | Bin-Jaliah, (2021) | |
| Wistar rats | CUMS | p.o | 25, 50 mg/kg | FST, OFT, fluid consumption test | Quercetin reduced the immobility time in FST, augmenting the number of line crossings, total distance traveled, the number of entries in left zone and time in the left zone in OFT. | Quraishi et al. (2018) | |
| Wistar rats | DMH induces colorectal cancer | p.o | 50 mg/kg | FST, OFT | Quercetin reduced the immobility time of mice in FST, increasing walking and feeding frequency in OFT. | Sadighparvar et al. (2020) | |
| Wistar rats | OB | p.o | 20, 40 mg/kg | FST, OFT | Quercetin reduced ambulation, rearing, defecation and increased the grooming/licking episodes in OFT, reducing the characteristic hyperactivity and the immobility time in FST. | Rinwa and Kumar, (2013) | |
| Wistar rats | Rotenone intervention | p.o | 50 mg/kg | SPT, OFT, NOR, MWM, beam walking test, inclined plane test, footprint test, social interaction test | Quercetin increased the intake of sugar in SPT, reduced the latency to move and increased the number of squares crossed in OFT. | Madiha et al. (2021) | |
| Wistar albino rats | CUMS | i.p | 30 mg/kg | FST, SPT, locomotor activity | Quercetin reduced the immobility time in FST, improving sucrose preference in SPT. | Şahin et al. (2020) | |
| Wistar albino rats (pregnant) | NaF intervention | p.o | 20 mg/kg | OFT, maze learning test, levels of monoamines | Quercetin increased head elevation, hind limb elevation, sniffing, grooming, auditory startle, pivoting scores of animals in OFT, restoring the levels of Ach in the cerebral cortex of developing rat brain | Mesram et al. (2017) | |
| Zebrafish | Danio rerio zebrafish | LPS intervention | i.p | 50, 100 mg/kg | Novel tank diving test, light–dark chamber test, inflammation examination and antioxidant enzyme activity | Quercetin increased the time spent in the top zone and the number of entries in the top zone in novel tank diving test, increasing the time spent in the light zone and the number of entries in the light zone in the light–dark chamber test | Singh et al. (2022) |
| Danio rerio zebrafish | Bisphenol A intervention | Directly spiked into water | 2.96 μM | Novel tank diving test, light/dark preference test | Quercetin ameliorated the BPA-induced alteration in time spent in top zone, the number of transitions to top zone and latency to enter top zone in novel tank diving test | Sahoo et al. (2020) | |
| Danio rerio zebrafish | Aluminum chloride intervention | Directly spiked into water | 2 μl | Novel tank test, light/dark preference test, native area test | Quercetin increased the time spent in the top zone in novel tank test | Mani et al. (2018) | |
| Wild-type zebrafish | — | Directly spiked into water | 0.01, 0.1, 1, 10, 100, 1,000 μg/L | Novel tank test, shoaling behavior test, anxiety behavior test | Quercetin increased the shoaling tendency and the latency to enter the upper half in shoaling behavior test, increasing the total time in the upper and the total number of midline transitions in the anxiety behavior test | Zhang et al. (2020a) |
SPT, sucrose preference test; FST, forced swimming test; MFST, modified forced swimming test; TST, tail suspension test; OFT, open field test; LDA, light and dark box test; EPM, elevated plus maze; NOR, novel object recognition test; NMRI, Naval Medical Research Institute; CUMS, chronic unpredictable mild stress; CUS, chronic unpredictable stress; MS, maternal separation procedure; CSDS, chronic social defeated stress; OB, olfactory bulbectomy; TNF, tumor necrosis factor; IL, Interleukin; SOD, superoxide dismutase; CAT, catalase; GSH, glutathione; MDA, malondialdehyde; GPx, glutathione peroxidase; MAO, Monoamine oxidase; 5-HT, serotonin; BDNF, Brain-derived neurotrophic factor; HPA, hypothalamic-pituitary-adrenal; ACTH, adrenocorticotropic hormone; CORT, corticosterone; Ach, acetylcholine; AchE, acetylcholinesterase; LPS, Lipopolysaccharide; DMH, Dimethyl hydrazine; mTBI, Mild Traumatic Brain Injury; ADR, adriamycin; GBH, glyphosate-based herbicide; CRF, corticotrophin releasing factor; TrkB, Tyrosine Kinase receptor B; AKT, decreased protein kinase B; ERK1/2, extracellular regulated protein kinases; NaF, Sodium fluoride; KM, Kunming; ICR, Institute of Cancer Research; SD, Sprague Dawley.