TABLE 2.
Overview of citrus flavonoids on cognitive performance and locomotor activity in preclinical models.
| Citrus polyphenol | Behavioral test performance | Reported effective Dose (mg/kg) | Model summary/References |
| Hesperidin | No change locomotor activity (OF), ↓anxiety-like behavior (EPM), ↓depressive symptoms (splash test) | 50 (28 days) | Intrastriatal injection 6-OHD, 3–6-month adult male C57BL/6 mouse (Antunes et al., 2020) |
| ↓Anxiety-like behavior (EPM, OF), ↓Depressive symptoms (FST) | 50, 150 (10 weeks) Dose dependent with 150 more effective | I.P injection STZ, adult male Sprague Dawley rat (Zhu et al., 2020) | |
| ↓Anhedonia (SPT), ↓Depressive symptoms (TST and FST), ↓Anxiety-like behavior (OF) | 100 and 200 (three times a week for 3 weeks) | Chronic unpredictable mild stress, 6–8-week ICR male mouse (Fu et al., 2019) | |
| ↑Recognition memory (NOL and NOR) | 100 (21 days) | IV injection Methotrexate, male Sprague Dawley rat (Naewla et al., 2019) | |
| ↓Anhedonia (SPT), ↓Depressive symptoms (TST, FST, Novelty-suppressed feeding) | 50 (14 days) | Concussive head injury, 10-11-week male NMRI mouse (Kosari-Nasab et al., 2018) | |
| ↑Spatial learning and memory (MWM and Y maze) | 25, 50, 100 (14 days). Dose dependent with 50 and 100 more effective | L-Methionine treated, male Wistar rat (Hemanth Kumar et al., 2017) | |
| ↓Depressive symptoms (TST and FST) | 100 (60 days) | I.P. AlCl3, 10-12-week male albino Wistar rat (Justin Thenmozhi et al., 2017) | |
| ↓Anxiety-like behavior (OF), ↓Depressive symptoms (FST, rearing, grooming, splash test), ↑Spatial learning and memory (MWM), ↑Recognition memory (NOR) | 50 (14 days) | Olfactory bulbectomy, male C57BL/6 mouse (Antunes et al., 2016) | |
| ↓Anhedonia (SPT), ↓Depressive symptoms (FST), No change OF | 25, 50, 100 (7 days) | I.P. LPS, male ICR mouse (Li M. et al., 2016) | |
| ↓Anhedonia (SPT), ↓Depressive symptoms (FST) | 25, 50 (3 weeks) | Chronic mild stress, 5-week male ICR mouse (Li C. F. et al., 2016) | |
| ↑Social behavior (Nest building, resident-intruder assay) | 100 (10 days) | Transgenic APP/PS1–21, 5-month male mouse (Li et al., 2015) | |
| ↑Spatial learning and memory (MWM) | 100 and 200 (15 days) | Intracerebroventricular injection STZ, 12-month Swiss male albino mouse (Javed et al., 2015) | |
| ↓Depressive symptoms (FST) | 25, 50, 100 (21 days) | I.P. STZ, male albino Wistar rat (El-Marasy et al., 2014) | |
| ↓Abnormal thigmotaxis (OF), ↑Recognition memory (NOR), Spatial reference learning and memory (MWM) | 50, 100 (16 weeks) Dose dependent with 100 more effective | APPswe/PS1dE9, 3-month male mouse (Wang et al., 2014) | |
| ↓Depressive symptoms (TST), ↓Spatial memory (MWM), No change OF | 50 (28 days) | Intracerebroventricular injection 6-OHDA, female C57 BL/6 mouse (Antunes et al., 2014) | |
| Hesperetin | ↑Spatial learning and memory (MWM and Y-Maze) | 50 (5 weeks) | I.P. LPS, 7–8-week male C57BL/6N mouse (Muhammad et al., 2019) |
| ↑Recognition memory (NOR), ↑Spatial learning and memory (MWM) | 5, 50 (3 days) | I.P. scopolamine, male albino mouse (Ishola et al., 2019) | |
| ↑Recognition memory (NOR), ↑Associative memory (PAT) | 10, 20 (3 weeks) | I.P. STZ male Wistar rat (Kheradmand et al., 2018) | |
| Naringenin | ↑Spatial learning and memory (MWM and Barnes maze) | 250-300 (10 weeks) | High-fat diet-fed, 10-month SAMP8 male mouse (Zhou et al., 2020) |
| ↑Spatial learning and memory (MWM), ↑Recognition memory (NOR), ↑Associative memory (PAT), ↑Working memory (EPM), ↑Social behavior, ↓Depressive symptoms (FST) | 50 (14 days) | I.P. AlCl3 + D-gal injection, young albino Wistar rat (Haider et al., 2020) | |
| ↑Spatial learning and memory (MWM), ↑Recognition memory (NOR) | 100 (15 days) | Oral MeHg, 5-week male Swiss albino mouse (Krishna Chandran et al., 2019) | |
| ↓Anxiety-like behavior (OF), ↓Depressive symptoms (FST), ↑Spatial learning and memory (MWM) | 50 (4 weeks) | Chronic unpredictable mild stress, adult male Wistar rat (Tayyab et al., 2019) | |
| ↓Anhedonia (SPT), ↓Depressive symptoms (TST and FST) | 25, 50, 100 (5 days) Dose dependent with 50 and 100 more effective | Bilateral olfactory bulbectomy, 3-month BALB/c male mouse (Bansal et al., 2018) | |
| ↑Spatial learning and memory (Y-maze, ↑Recognition memory (NOR), ↑Associative memory (PAT) | 50, 100 (7 days) | I.P. LPS male albino Wistar rat (Khajevand-Khazaei et al., 2018) | |
| ↑Motor Function (beam walk, vertical grid, horizontal grid) | 25, 50, 100 (5 days) | I.P. injection MPTP, male C57BL/6J mouse (Mani et al., 2018) | |
| ↑Spatial learning and memory (MWM) | 50 (16 days) | Young adult male albino Wistar rat (Liaquat et al., 2018) | |
| ↑Spatial learning and memory (Y-maze, RAM), ↑Associative memory (PAT) | 100 (single dose) | Dorsal hippocampal Aβ injection, adult male Wistar rat (Ghofrani et al., 2015) | |
| ↓Anhedonia (SPT), ↓Anxiety (Novelty-suppressed feeding test) | 10, 20 (3 weeks) | Chronic unpredictable mild stress, 5-week male ICR mouse (Yi et al., 2014) | |
| ↑Spatial learning and memory (MWM) | 25, 50, 100 (21 days) | Intracerebroventricular injection, STZ adult male Sprague Dawley rat (Yang W. et al., 2014) | |
| ↑Motor Function (Rota rod, Grip test, Adhesive-removal test) | 50 (21 days) | Middle cerebral artery occlusion, 16-week male Wistar rat (Raza et al., 2013) | |
| Naringin | ↑Locomotor activity (Rotarod, Beam-crossing, footprint analyses), ↓Depressive symptoms (Grooming) | 40 and 80↑(28 days) | Intrastriatal injection quinolinic acid, adult male Sprague-Dawley rat (Cui et al., 2018) |
| ↑Motor/locomotor activity (Horizontal Bar, Spontaneous Motility, Forelimb Flexion, Righting Reflex, Actophotometer, Rotarod, Paw withdrawal) ↓Depressive symptoms (FST) ↑Spatial learning and memory (MWM) | 20 and 40 (28 days) Dose dependent 40 most effective | Intastriatal injection collagenase, adult female Wistar rat (Singh et al., 2017) | |
| ↓Motor abnormalities (Hind limb function test, Grip strength test, Print length analysis) | 80 (14 days) | I.P. 3-nitropropionic acid, male Wistar rat (Gopinath and Sudhandiran, 2016) | |
| ↑Spatial learning and memory (MWM), ↑Recognition memory (NOR) | 100 (20 weeks) | High-fat diet induced cognitive decline, male C57BL/6 mouse (Wang et al., 2015b) | |
| ↓Anxiety-like behavior (OF, elevated T maze) | 25, 50, 100 (5 weeks) Dose dependent with 100 most effective | Cisplatin exposed, middle aged Wistar rat (Chtourou et al., 2015) | |
| ↑Spatial learning and memory (MWM) ↑Working memory (EPM) | 50, 100, and 200 (21 days) | Intracerebroventricular STZ, adult male Wistar rats (Sachdeva et al., 2014) | |
| Kaempferol | ↑Sensorimotor behaviors (Whisker stimulation-induced motor response, Forelimb usage test) | 1 (three times: 1, 24, 48 h) | Traumatic Brain Injury, 23–24-day male Sprague-Dawley rat (Chitturi et al., 2019) |
| ↑Spatial learning and memory (Y-maze), ↑Recognition memory (NOR) | 21 (14 days) | I.P. Chlorpyrifos daily for 14 days, 8-week male albino Wistar rat (Hussein et al., 2018) | |
| ↑Spatial learning and memory (MWM) | 10 (21 days) | Intracerebroventricular injection STZ, OVX female Wistar rats (Kouhestani et al., 2018) |