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ORIGINAL ARTICLE
Year : 2018  |  Volume : 17  |  Issue : 1  |  Page : 14-18

A new horizon into the central effect of quercetin on human vigilance in normal healthy volunteers


Department of Pharmacology, Toxicology, and Medicine, College of Medicine, Al-Mustansiriyah University, Baghdad, Iraq

Date of Web Publication25-Jul-2018

Correspondence Address:
Dr. Ali Kadhim Al-Buhadilly
Department of Pharmacology, Toxicology, and Medicine, College of Medicine, Al-Mustansiriyah University, P.O. Box. 14132, Baghdad
Iraq
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/MJ.MJ_2_18

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  Abstract 

Background: Quercetin is one of the dietary flavonoids found in citrus fruits and leafy vegetables as well as seeds and green tea. Its name comes from Quercetum and belongs to flavonol class which is not synthesized in the human body. Many studies revealed a significant effect of quercetin in advancing psychomotor/cognitive performances and reversing the neurotoxin-induced neuronal damage. Therefore, the present study aimed to illustrate the central effect of quercetin on human vigilance and in normal healthy volunteers. Subjects and Methods: A total of fifty healthy volunteers with a mean age of 23 years were enrolled in this experimental study; they were divided into two groups: Group I: twenty healthy volunteers treated with placebo (500 mg/day starch capsule) for 2 weeks and Group II: thirty healthy volunteers treated with quercetin 500 mg/day for 2 weeks. Each volunteer in each group was subjected to vigilance-psychomotor testing by Leeds psychomotor performance tester which measures Psychomotor-vigilance test (PVT) and Cortical arousal activity (CAA). Results: Quercetin produced a more significant effect on total reaction time, recognition reaction time, movement reaction time, fusion index, % fusion (P < 0.01), and flicker percentage (P < 0.05) compared to control, but quercetin produced an insignificant effect on CFFd, critical flicker-fusion frequency, and flicker index. Conclusion: Quercetin improves psychomotor performance and CAA in normal healthy volunteers.

Keywords: Cortical arousal activity, critical flicker-fusion frequency, psychomotor performance, quercetin


How to cite this article:
Al-Buhadilly AK. A new horizon into the central effect of quercetin on human vigilance in normal healthy volunteers. Mustansiriya Med J 2018;17:14-8

How to cite this URL:
Al-Buhadilly AK. A new horizon into the central effect of quercetin on human vigilance in normal healthy volunteers. Mustansiriya Med J [serial online] 2018 [cited 2018 Nov 16];17:14-8. Available from: http://www.mmjonweb.org/text.asp?2018/17/1/14/237549


  Introduction Top


Quercetin is one of the dietary flavonoids found in citrus fruits and leafy vegetables as well as seeds and green tea. Its name comes from Quercetum and belongs to flavonol class which is not synthesized in the human body. Quercetin is a lipid-soluble bioflavonoid used as a nutritional supplement against different diseases and acts as anti-bacterial, immunomodulator, anti-hypertensive, anti-diabetic, and other metabolic disorders.[1]

Moreover, quercetin exerts a neuroprotective effect through modulation of neuro-inflammatory injury and prevents age-linked neurodegeneration; thus, it plays an important role in the modulation of the progression of Parkinson's and Alzheimer's diseases.[2]

Indeed, quercetin improves cerebral blood flow, stimulates angiogenesis, and acts as an activator for neurogenesis when used in the management of cerebral stroke. Many studies revealed a significant effect of quercetin in advancing psychomotor/cognitive performances and reversing the neurotoxin-induced neuronal damage. Additionally, mice fed on flavonoid-rich diet are linked with good cognitive function.[3],[4]

In addition, quercetin has strong anti-oxidant effect that lessens the incidence and occurrence of free radical and oxidative-induced neuronal injury, so quercetin along with other anti-oxidant vitamins is used successfully in the amelioration of neurodegenerative diseases.[5]

On the other hand, a study reported that most of the licensed psychotropic drugs prior to 2007 were synthetic although a new trend for neuroprotective drugs should involve natural agents in the amelioration of human cognitive function and attenuation of psychomotor retardation.[6]

Since there are only little studies regarding the effect of quercetin on the cognitive function of normal healthy human volunteers, this study is warranted to expose the central effect of quercetin. Therefore, the present study aimed to illustrate the central effect of quercetin on human vigilance and in normal healthy volunteers.


  Subjects and Methods Top


This study was conducted at the Department of Clinical Pharmacology and Therapeutics, College of Medicine, Al-Mustansiriyah University, in April 2016. This was a double-blind, randomized, placebo-controlled study involving fifty healthy volunteers recruited from medical students of College of Medicine. The enrolled volunteers gave informed verbal and written consent for their participation in this study. Protocol of this study was approved by the scientific committee on the College of Medicine, Al-Mustansiriyah University. Human care and research procedures were done according to the Declaration of Helsinki.[7]

Study design

A total of fifty healthy volunteers with a mean age of 23 years (20 females + 30 males) were enrolled in this experimental study; they were divided into two groups as follows:

  • Group I – Twenty healthy volunteers (11 males + 9 females) treated with placebo (500 mg/day starch capsule) for 2 weeks
  • Group II – Thirty healthy volunteers (19 males + 11 females) treated with quercetin 500 mg/day (Lamberts tablet, USA) for 2 weeks.


Inclusion criteria

Healthy young volunteers without any obvious disease, not taking any medication at least within 1 week, nonalcoholic, or not taking a caffeinated beverage were included in the study.

Exclusion criteria

Any volunteer with eye disorders or on eyeglasses and those with psychiatric, neurological, and metabolic diseases were excluded from the study. In addition, a volunteer with simple tremor or obesity was also excluded from this study.

Each volunteer in each group was subjected to vigilance-psychomotor testing by Leeds psychomotor performance tester which measures the following:

Psychomotor-vigilance test

Psychomotor-vigilance test (PVT) involved three main components including total reaction time (TRT), recognition reaction time (RRT), and movement reaction time (MRT) all measured in milliseconds. TRT represents the total time needed by each volunteer from recognition of visual stimuli to the end of the motor action. RRT represents the time needed by a volunteer from recognition of visual stimuli to the beginning of the motor action. MRT represents the time needed by a volunteer from the end of recognition of visual stimuli to the end of the motor action.

Both TRT and RRT were displayed on the digital screen of Leed psychomotor tester, while MRT value was obtained by subtraction of RRT from TRT.[8]

Cortical arousal activity

Critical flicker-fusion frequency (CFFF) measures the cortical arousal activity (CAA) of each volunteer. The components of CFFF include critical fusion frequency and critical flicker frequency. Critical fusion frequency, also called ascending frequency (CFF A), measures the time needed in seconds by a volunteer for awareness of flicker red illuminated light to be fused (awareness of flicker to be steady). Critical flicker frequency, also called descending frequency (CFF d), measures the time needed in seconds by a volunteer for awareness of fusion red light to be flickered. Better value for CFF A should be >30 Hz and better value for CFF d should be <30 Hz.[9],[10]

Other parameters of CAA can be calculated from CFF A and CFF d as follows:

  • Flicker index = (minimum and maximum values in CFF d)
  • Fusion index = (minimum and maximum values in CFF A)
  • %Flicker = (minimum and maximum values in CFF d)
  • %Fusion = (minimum and maximum values in CFF A)
  • CFFF=


  • These neurocognitive tests were assessed at baseline (before taking quercetin or placebo) and then second measurements after 2 weeks were also taken to illustrate the effect of quercetin and placebo, all procedures were done at 8–10 am to exclude diurnal variations.

    Statistical analysis

    All data were presented as mean ± standard deviation, and paired and unpaired Student's t-test was used to measure the significance of differences regarding P < 0.05 as significant.


      Results Top


    Demographic characteristics of this study are illustrated in [Table 1].
    Table 1: Demographic characteristics of the enrolled volunteers

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    Consort flow diagram of the present study revealed that four volunteers were excluded from this study, while the fifty volunteers continued the course of the study without any withdrawal rate [Figure 1].
    Figure 1: Consort flow diagram of the present study

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    Regarding the effect of placebo and quercetin on the psychomotor variables, quercetin produced significant reduction in TRT, MRT, RRT, flicker index, and% fusion with P < 0.01, whereas the placebo effect only reduced MRT from 195.94 ± 12.64 to 185.00 ± 12.55 ms (P< 0.01), less significant effect of quercetin on CFF A and CFF d (P< 0.05), and without significant effect on other psychomotor variables (P > 0.05) [Table 2].
    Table 2: Effect of placebo and control on the psychomotor variables

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    Quercetin produced a more significant effect on TRT, RRT, MRT, fusion index, % fusion (P< 0.01), and %flicker index (P< 0.05) compared to control, but quercetin produced an insignificant effect on CFF d, CFFF, and flicker index [Table 3].
    Table 3: Differential effects of quercetin on psychomotor variables compared to the control

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    On the other hand, there were insignificant gender differences in the central effect of quercetin (P > 0.05) [Figure 2].
    Figure 2: Insignificant gender differences in the central effect of quercetin

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      Discussion Top


    PVT and CFFF parameters are reliable neurocognitive tests to estimate the vigilance and CAA, respectively.[11] These tests are affected by different factors including age, health status, race, and age.[12] These factors were excluded from this study since all the enrolled volunteers were healthy, younger, and of the same race.

    The present study illustrated significant improvement effect of quercetin on most of the vigilance and CAA variables compared to the control, which was confirmed by Neha et al's. study that demonstrated a significant effect of quercetin in advancing psychomotor performance due to the antistress effect of quercetin in the animal model study.[13] In contrast, some positive stress (eu-stress) created a potential improvement of human vigilance and CAA [14]

    Recently, Bahar et al's. study showed that quercetin led to significant neurobehavioral effect via anti-oxidant activity and prevention of neuroinflammation induced by manganese, so it produced a potential neuroprotective effect through attenuation of oxidative stress.[15] Therefore, most of the anti-oxidant herbal agents produce an acceleration of cognitive function and memory function as revealed by the study by Al-Kuraishy (2015) that disclosed the noteworthy effect of Ginkgo biloba and/or Rhodiola rosea on vigilance and working memory due to anti-oxidant effects.[16] Oxidative stress markers were not evaluated in this study since all the enrolled volunteers were healthy and not smokers.

    Quercetin in this experimental study produced differential effects on CAA variables as it accelerates CFF A, but it created an insignificant effect on CFF d and CFFF which means that there are different neuronal pathways involved in human arousal capability.[17] In addition, this differential effect of quercetin may be due to selective activation of brain regions as recently revealed by a study by Mehta et al. that divulged the selective effect of quercetin on hippocampus which per se attenuates locomotor deficit and behavioral dysfunction induced in mice.[18] Moreover, Nassiri-Asl et al. demonstrated a dose-dependent effect of quercetin in quickening the psychomotor performances and acceleration of step-through latency of passive avoidance during experimental kindling in rats.[19] Thus, the present study is in agreement with most of the recent studies that exemplified the nootropic effect of quercetin in the improvement of psychomotor vigilance task and human arousal facility.[20],[21]

    The possible explanation of the central stimulant effect of quercetin may be through inhibition of acetylcholinesterase (AchE) that involved in the degradation of central acetylcholine as revealed by Szwajgier's study which showed that flavonols of quercetin cause considerable inhibition of brain AchE.[22] Indeed, phenolic constituents of quercetin lead to attenuation of cognitive dysfunction.[23] Consequently, inhibition of AchE and anti-oxidant effect are the main pathways involved in the activation of human vigilance and arousal variables, but AchE was not measured in the present study.

    On the other hand, placebo in the present study showed significant improvement effect on MRT as described by Kurdi and Muthukalai's study which illustrated that placebo may improve psychomotor performance and decrease preoperative anxiety.[24] Besides, the placebo effect might affect both negative and positive directions during vigilance test, which may explain the specific expectation effect on human psychomotor performance.[25] Certainly, Al-Greeb's study showed that neither nutraceuticals nor placebo produced a significant effect on psychomotor performance and the significant effect might be due to the nocebo effect.[26] A study by Ashor (2012) confirmed the differential effect of placebo on human psychomotor performance; when placebo is known as a stimulant, it enhanced psychomotor performance and working memory; when placebo is unknown, it deteriorates only working memory; but when a placebo is known as inert, it produces an insignificant effect, thus placebo effect is related to the volunteer expectation.[27]


      Conclusion Top


    Quercetin improves psychomotor performance and CAA in normal healthy volunteers.

    Financial support and sponsorship

    Nil.

    Conflicts of interest

    There are no conflicts of interest.

     
      References Top

    1.
    Barreca D, Bellocco E, D'Onofrio G, Nabavi SF, Daglia M, Rastrelli L, et al. Neuroprotective effects of quercetin: From chemistry to medicine. CNS Neurol Disord Drug Targets 2016;15:964-75.  Back to cited text no. 1
        
    2.
    Xia SF, Xie ZX, Qiao Y, Li LR, Cheng XR, Tang X, et al. Differential effects of quercetin on hippocampus-dependent learning and memory in mice fed with different diets related with oxidative stress. Physiol Behav 2015;138:325-31.  Back to cited text no. 2
        
    3.
    Chakraborty J, Rajamma U, Jana N, Mohanakumar KP. Quercetin improves the activity of the ubiquitin-proteasomal system in 150Q mutated Huntington-expressing cells but exerts detrimental effects on neuronal survivability. J Neurosci Res 2015;93:1581-91.  Back to cited text no. 3
        
    4.
    Zhang ZJ, Cheang LC, Wang MW, Lee SM. Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish. Int J Mol Med 2011;27:195-203.  Back to cited text no. 4
        
    5.
    Singh S, Jamwal S, Kumar P. Neuroprotective potential of quercetin in combination with piperine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. Neural Regen Res 2017;12:1137-44.  Back to cited text no. 5
    [PUBMED]  [Full text]  
    6.
    Ojizeh I, Eghafona O. Nutritional and physicochemical profiles of some indigenous extracts used in alternative medicine. J Intercult Ethnopharmacol 2014;3:29-36.  Back to cited text no. 6
        
    7.
    Puri KS, Suresh KR, Gogtay NJ, Thatte UM. Declaration of Helsinki, 2008: Implications for stakeholders in research. J Postgrad Med 2009;55:131-4.  Back to cited text no. 7
    [PUBMED]  [Full text]  
    8.
    Al-Kuraishy HM, Al-Gareeb AI, Ashor AW. Effect of a single dose of dextromethorphan on psychomotor performance and working memory capacity. Indian J Psychol Med 2012;34:140-3.  Back to cited text no. 8
    [PUBMED]  [Full text]  
    9.
    Al-Kuraishy HM, Al-Gareeb AI. Central beneficial effects of trimetazidine on psychomotor performance in normal healthy volunteers. Adv Biomed Res 2017;6:69.  Back to cited text no. 9
    [PUBMED]  [Full text]  
    10.
    Al-Kuraishy HM, Al-Gareeb AI. Co-administration effects of α-lipoic acid and nucleo CMP on arousal and sensory cortical activity. J Young Pharm 2016;8:12-7.  Back to cited text no. 10
        
    11.
    Honn KA, Riedy SM, Grant DA. Validation of a portable, touch-screen psychomotor vigilance test. Aerosp Med Hum Perform 2015;86:428-34.  Back to cited text no. 11
        
    12.
    Hu Z, Sun Y, Lim J, Thakor N, Bezerianos A. Investigating the correlation between the neural activity and task performance in a psychomotor vigilance test. Conf Proc IEEE Eng Med Biol Soc 2015;2015:4725-8.  Back to cited text no. 12
        
    13.
    Neha T, Ashutosh M, Ganesh B, Anil C. Anti-stress Activity of a Bioflavanoid: Quercetin from Euphorbia hirta. British Journal of Pharmaceutical Research 2015;6:68-75.  Back to cited text no. 13
        
    14.
    Al-Kuraishy HM, Al-Gareeb AI. Eustress and malondialdehyde (MDA): Role of panax ginseng: Randomized placebo controlled study. Iran J Psychiatry 2017;12:194-200.  Back to cited text no. 14
        
    15.
    Bahar E, Kim JY, Yoon H. Quercetin attenuates manganese-induced neuroinflammation by alleviating oxidative stress through regulation of apoptosis, iNOS/NF-κB and HO-1/Nrf2 pathways. Int J Mol Sci 2017;18. pii: E1989.  Back to cited text no. 15
        
    16.
    Al-Kuraishy HM. Central additive effect of Ginkgo biloba and Rhodiola rosea on psychomotor vigilance task and short-term working memory accuracy. J Intercult Ethnopharmacol 2016;5:7-13.  Back to cited text no. 16
        
    17.
    Kot J, Winklewski PJ, Sicko Z, Tkachenko Y. Effect of oxygen on neuronal excitability measured by critical flicker fusion frequency is dose dependent. J Clin Exp Neuropsychol 2015;37:276-84.  Back to cited text no. 17
        
    18.
    Mehta V, Parashar A, Udayabanu M. Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress. Physiol Behav 2017;171:69-78.  Back to cited text no. 18
        
    19.
    Nassiri-Asl M, Moghbelinejad S, Abbasi E, Yonesi F, Haghighi MR, Lotfizadeh M, et al. Effects of quercetin on oxidative stress and memory retrieval in kindled rats. Epilepsy Behav 2013;28:151-5.  Back to cited text no. 19
        
    20.
    Moreno LC, Puerta E, Suárez-Santiago JE, Santos-Magalhães NS, Ramirez MJ, Irache JM, et al. Effect of the oral administration of nanoencapsulated quercetin on a mouse model of alzheimer's disease. Int J Pharm 2017;517:50-7.  Back to cited text no. 20
        
    21.
    Singh V, Kahol A, Singh IP, Saraf I, Shri R. Evaluation of anti-amnesic effect of extracts of selected ocimum species using in-vitro and in-vivo models. J Ethnopharmacol 2016;193:490-9.  Back to cited text no. 21
        
    22.
    Szwajgier D. Anticholinesterase activity of selected phenolic acids and flavonoids – Interaction testing in model solutions. Ann Agric Environ Med 2015;22:690-4.  Back to cited text no. 22
        
    23.
    Szwajgier D, Baranowska-Wojcik E, Borowiec K. Phenolic acids exert anticholinesterase and cognition-improving effects. Curr Alzheimer Res 2018;15:531-43.  Back to cited text no. 23
        
    24.
    Kurdi MS, Muthukalai SP. A comparison of the effect of two doses of oral melatonin with oral midazolam and placebo on pre-operative anxiety, cognition and psychomotor function in children: A randomised double-blind study. Indian J Anaesth 2016;60:744-50.  Back to cited text no. 24
    [PUBMED]  [Full text]  
    25.
    Draganich C, Erdal K. Placebo sleep affects cognitive functioning. J Exp Psychol Learn Mem Cogn 2014;40:857-64.  Back to cited text no. 25
        
    26.
    Al-Gareeb AI. The subtle central effect of nutraceuticals: Is it placebo or nocebo? J Intercult Ethnopharmacol 2015;4:221-3.  Back to cited text no. 26
        
    27.
    Ashor AW. The placebo effect on psychomotor performance and working memory capacity: Randomized single blind cross-over trial. Ann Neurosci 2011;18:141-4.  Back to cited text no. 27
        


        Figures

      [Figure 1], [Figure 2]
     
     
        Tables

      [Table 1], [Table 2], [Table 3]



     

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      In this article
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    Introduction
    Subjects and Methods
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