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CLINICAL RESEARCH
Year : 2015  |  Volume : 36  |  Issue : 1  |  Page : 56-62  

Randomized placebo-controlled clinical study on enhancement of Medha (intelligence quotient) in school going children with Yahstimadhu granules


1 Department of Kaumarabhritya, Mahatma Gandhi Ayurved College, Hospital and Research Centre, Wardha, Maharashtra, India
2 Department of Kaumarabhritya, Institute for Post Graduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar, Gujarat, India

Date of Web Publication4-Nov-2015

Correspondence Address:
Srihari Sheshagiri
Asst. Professor, Department of Kaumarabhritya, Mahatma Gandhi Ayurved College, Hospital and Research Centre, Wardha - 442 001, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-8520.169011

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   Abstract 

Introduction: Optimal intelligence is a vital essentiality in day-to-day life, especially in children who have to build up their life in an apt manner. Yashtimadhu (Glycyrrhiza glabra Linn) is a time tested classical drug indicated for promotion of mental health mentioned in Ayurveda which may also help children to attain optimal intelligence. Aim: To evaluate the role of Yashtimadhu (Glycyrrhiza glabra Linn.) granules in enhancement of Medha (intelligence quotient [IQ]). Materials and Methods: The study was conducted on healthy school going children aged 14–16 years. Total 94 children were registered and divided into two groups. Yashtimadhu granules was administered in Group A and Wheat flour in the form of granules in Group B, the duration of treatment was 12 weeks with follow up of additional 12 weeks. Objective parameters included assessment of functional aspects of Buddhi (psychological faculty for reasoning and logic) along with the assessment of IQ, Quality of life parameters and general health condition. Results: Yashtimadhu granules showed statistically highly significant results in improving functional aspects of Buddhi, IQ, several aspects of quality of life parameters and health. The number needed to treat (NNT) with Yashtimadhu granules for children achieving an IQ score of 90 and above was 3.38, suggesting one in every 3.38 patients had achieved this target and for children achieving an IQ score of 110 and above the NNT was 6.66. Conclusion: Yashtimadhu granules was safe throughout the course of study and indeed possessed a significant efficacy in improving Medha (IQ).

Keywords: Children, intelligence quotient, Medha, Yashtimadhu granules


How to cite this article:
Sheshagiri S, Patel KS, Rajagopala S. Randomized placebo-controlled clinical study on enhancement of Medha (intelligence quotient) in school going children with Yahstimadhu granules. AYU 2015;36:56-62

How to cite this URL:
Sheshagiri S, Patel KS, Rajagopala S. Randomized placebo-controlled clinical study on enhancement of Medha (intelligence quotient) in school going children with Yahstimadhu granules. AYU [serial online] 2015 [cited 2023 Mar 24];36:56-62. Available from: https://www.ayujournal.org/text.asp?2015/36/1/56/169011


   Introduction Top


The memory demands for school age children are much greater than they are for adults and are continuously fed with new knowledge in various areas, which might be interesting or not to them. Moreover, children are expected to learn and remember them and repeat it during exams. Except when there is a marked deviation from the normal, young children are not aware of what their intellectual level is. The bright, for example, do not realize how bright they are, the dull are unaware of their dullness, and the average take their intelligence for granted. After they enter the school, children measure their level of intellectual power by the kind of adjustment they make to school work.[1]

Intelligence may be narrowly defined as the capacity to acquire knowledge and understanding, and used in different novel situations. It is this ability, or capacity, which enables the individual to deal with real situations and profit intellectually from sensory experience. Although it is difficult to define intelligence, indeed it appears to have no formal definition, there is, nevertheless, at least one particularly apposite definition: The capacity to learn and understand.[2]

In the Ayurvedic classics, the word "Buddhi" is used in many contexts. On studying it's literally meaning, (Nirukti and Vyutpatti) it can be understood as the psychological faculty for reasoning and logic. However, after critical analysis of classics, it is evident that at many places it has been used as an advance stage or as a process leading to a true knowledge. Buddhi is described as Jnana (knowledge).[3] The word "Medha" has been used mainly in two ways viz. Grahana Shakti (grasping power) and Dharana Shakti (retention power).[4] Besides this, Buddhi, Smriti, Dhi, etc., words have been used in a similar sense at many places.

Concept of improving cognitive functions like intelligence and memory is relatively very new to current modern system of medicine. The first drug discovered to enhance cognitive functions known as "Nootropics" were in 1972.[5] Knowledge of natural herbal drugs possessing cognitive enhancing activity dates back to thousands of century back. "Medhya Rasayana" is a specific group of four, time-tested classical preparations for promotion of mental health and well-being.[6]Yashtimadhu (Glycyrrhiza glabra Linn.) is one among them mentioned for these purpose by Acharya Charaka.[6]

Abundant works have been carried out on varied systemic actions of Yashtimadhu in different disorders. Despite its mentioning as a potent Medhya Dravya by ancient scholars, only a fewer works have been carried out on the same until date. In this regard, Ayurveda has a potential to make a significant contribution with a potent and cost-effective Medhya Dravya.

There are a number of different methods, which contend to measure intelligence, the most famous of which is the intelligence quotient (IQ), or IQ test.[1] The IQ is a score derived from one of several standardized tests designed carefully to assess intelligence. The method of testing Medha is explained as "Grahanenaiti Granthadi Dharanena"[4] that is, understanding the ability of the person to understand, grasp, remember, and recall the Granthas (books) after reading.

By considering the above facts, this study has been undertaken to assess the efficacy of Yashtimadhu in enhancement of IQ in school going children.


   Materials and Methods Top


Healthy school going children of 9th and 10th standard (aged 14–16 years) of either sex irrespective caste, religion, and socioeconomic status were duly registered in the outpatient department of Kaumarabhritya Department. The study was started after obtaining the consent of the patients. The written consent was detailed in the local language and explained orally too regarding the type and course of study. The clinical study was started after the approval of Institutional Ethics Committee (No. PGT/7-A/Ethics/2010–2011/3381) and the research work has been registered in Clinical Trial Registry of India (CTRI)-CTRI/2011/11/002136 (Registered on: 16/11/2011)-retrospectively. It is a randomized (random number table method), placebo-controlled clinical study.

Inclusion criteria

Children of 9th and 10th standard (aged 14–16 years) with IQ score ranging 70–109 (Scores obtained after conducting verbal and performance subtests) were included.

Exclusion criteria

Children suffering from any systemic disorders, which may turn out to be hindrance in the study

Grouping and posology

The subjects included in the clinical trial were be divided into two groups namely,

  • Group A (Trial group) – Yashtimadhu granules in the dose of 12g per day with luke warm milk [6],[7]
  • Group B (Placebo controlled group) –Wheat flour in the form of granules in the dose of 12g per day with luke warm milk.


In both the groups drugs were administered in Apana Kala (before breakfast) for 12 weeks. Follow up study was conducted after 12 weeks of completion of treatment. Test drugs were prepared and procured from - Pharmacy, Gujarat Ayurved University, Jamnagar.

Laboratory investigation

Routine hematological, biochemical, urine, stool (routine and microscopic) investigations were carried to rule out any other pathological condition.

Assessment criteria

Effect of therapy was assessed by using following parameters-

  • 1. Medham Grahanena Score>


  1. Can grasp the event at an instance, no confusional status Score 3
  2. Can grasp the event at an instance but gets confused Score 2
  3. Delayed grasping with frequent confusion Score 1
  4. Grasping and understanding is difficult with lack of confusion Score 0


  • 2. Smritim Smaranena


  1. Both remote and recent memory are clear with easy retention and recall Score 3
  2. Both remote and recent memory clear but retention and recall are not seen Score 2
  3. Remote memory is impaired but recent memory is intact. Power of retention and recall not seen Score 1
  4. Both remote and recent memory are impaired With difficult retention and recall Score 0


  • 3. Dhriti Alaulyena


  1. Courageous on all occasions Score 3
  2. Courageous if supports are there Score 2
  3. Occasionally courageous if strong support is there Score 1
  4. No change at all Score 0


  • 4.Vijnana Vyavasayena




  1. Self efficient and sufficient to direct and do various activities himself Score 3
  2. Self efficient and sufficient to direct and do various activities with help of others Score 2
  3. Not self efficient and sufficient, guidance required in each and every work Score 1
  4. Cannot do or direct any activity with loss of insight Score 0


B. WHO quality of life parameters

Quality of life was assessed as per WHO guidelines.[8]

C. Rogi Bala (general health condition)

I.Agnibala

  1. 1. Abhyavaharana Shakti (capacity to ingest):Score

    1. Having food in good quantity twice/ thrice Score 6
    2. Having food in normal quantity twice a day Score 5
    3. Having food in moderate quantity twice a day Score 4
    4. Having food in less quantity twice a day Score 3
    5. Having food in less quantity once in a day Score 2
    6. Not at all having food Score 1


  2. 2. Jarana Shakti (capacity to digest):Scoring according to Jeerna Ahara Lakshaana present after 6-8 hrs after having food; Utsaha, Laghuta, Udgarashuddhi, Kshut Trishna Pravritti, Yathochita Malotsarga.

    Jarana Shakti: Score

    1. Absence of any symptom Score 1
    2. Presence of one symptom Score 2
    3. Presence of any two symptoms Score 3
    4. Presence of any three symptoms Score 4
    5. Presence of any four symptoms Score 5
    6. Presence of five symptoms Score 6


  3. 3.Ruchi Aharakale (capacity to relish taste while eating):

    1. Totally unwilling for meals Score 1
    2. Unwilling towards food but could take the meal Score 2
    3. Willing towards only most liking foods and not others Score 3
    4. Willing towards only one among Katu/ Amla/ Madhura foodstuffs Score 4
    5. Willing towards some specific Ahara/ Rasavishesha Score 5
    6. Equally willing towards all the Bhojya Padartha Score 6


  4. 4. Vata Mutra Retasam Mukti (frequency of bowel and urine evacuation):

    1. Passes stool after 3-4 days with Grathitha, Sakashta Malapravritti and having gaseous distension with Udgarapravritti Score 1
    2. Passes stool after 2-3 days having gaseous distension Score 2
    3. Can't pass stool daily and feeling heaviness in abdomen Score 3
    4. Difficulty in defecation, but daily with discomfort in abdomen Score 4
    5. Occurs easily in normal routine times Score 5




II. Dehabala

  1. 1. Balavriddhi (capacity for work):

    1. No weakness Score 1
    2. Slight weakness Score 2
    3. Feeling weakness but ability to work unaffected Score 3
    4. Ability to work affected Score 4
    5. Can't do any type of work Score 5


  2. 2. Swara Varna Yoga (accession of voice and complexion):

    1. Patient looks cheerful Score 1
    2. Lethargic and tired Score 2
    3. Looks gloomy Score 3


  3. 3. Sharira Upachaya (accession of body weight):

    1. No change Score 1
    2. Increase in weight by 2 kg Score 2
    3. Increase in weight by more than 2 kg Score 3




III. Satva / Chetas Bala

  1. 1. Nidra Labho Yathakalam (status of sleep):

    1. No sleep in day or night Score 1
    2. Disturbed sleep in night and tries to compensate in day Score 2
    3. Sleeps with disturbed intervals and remains unsatisfied Score 3
    4. Sleep gets disturbed in early morning Score4
    5. Sound sleep Score 5


  2. 2. Sukhena Cha Pratibodhanam (feeling of well being):

    1. Not feeling well and not interested in any work Score 1
    2. Improved in physical and mental level Score2
    3. Improved in physical comfort level Score 3
    4. Total relief and feeling of well being at physical and mental level Score 4


  3. 3. Vaikarikanam Cha Swapnanam Adarshanam (absence of discomforting dreams):



    1. Daily Score 1
    2. Occasionally Score 2
    3. Absent Score 3


  4. 4. Mano Buddhi Indriya Avyapatti (clarity of mind, intellect and sense organs):

    1. Loss of enthusiasm, concentration and vigour Score 1
    2. Less enthusiastic and not interested in routine work Score 2
    3. Less enthusiastic and not concentrating but interested in routine work Score 3
    4. Enthusiastic, vigorous, having concentration and interest in routine work Score 4


D. Intelligence quotient

Clinical response to medication was assessed based upon the objective parameter IQ (IQ test performance which was done before and after treatment). Scores obtained in each item from the score table of IQ subtests that is, verbal and performance scales were considered as the individual criteria.[8]

Assessment of total effect of therapy

The improvement in functional aspects of Buddhi, IQ scores, quality of life (QoL) parameters was considered in the final assessment along with the improvement in the general health condition viz. Dosha, Agni and Bala of the children.

Statistical analysis

Student 't' - test was the statistical tool used to assess and compare the efficacy of treatment.


   Observations Top


In this study, a total of 94 children were registered based on inclusion criteria. Fifty-one in Group A and forty three in Group B. Out of them forty in Group A and thirty five in Group B completed the treatment.

Males represented 43.15%, and females were 56.85% with a mean IQ score of 88.04 and 89.8 respectively. About 28.33% of children in the trial were aged between 15 and 16 years and had a comparatively higher mean of IQ score of 91.57 then other aged children. There were 4.35% of children belonging to upper socioeconomic status with a comparatively higher mean of IQ score 99.5 than their compatriots. About 10.5% of children were studying in private English medium school with a comparatively higher mean IQ score of 95.93%. Among these, 3.1% of children's father and mother were educated till master degree and had a higher mean IQ score of 102.4 and 95.27 respectively.


   Results Top


Efficacy on functional aspects of Buddhi

On comparing, the efficacy of trial drug and placebo drug over the functional aspects of Buddhi, trial drug Yashtimadhu granules showed statistically highly significant changes in increasing Medha (P < 0.0001), Smriti (P < 0.0005), Dhriti (P < 0.05) and Vijnana (P < 0.05) [Table 1].
Table 1: Comparative efficacy of Yashtimadhu and placebo granules on functional aspects of Buddhi

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Efficacy on WHO quality of life parameter

On comparing, the efficacy of trial drug and placebo drug over the WHO QOL parameter, Yashtimadhu granules showed statistically significant changes in improving physical health (P < 0.05) and highly significant results in improving psychological health (P < 0.001) on all other parameters, there were no significant changes between the two groups [Table 2].
Table 2: Comparative efficacy of Yashtimadhu and placebo granules on WHO QoL parameter

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Efficacy on general health condition

On comparing, the efficacy of trial drug and placebo drug on parameters of general health condition, trial drug provided statistically significant improvement by increasing Bala, Swara, Varna (complexion), Nidra, Sukhena Cha Pratibodhanam, and Mano Buddhi Indriya Avyapatti (P < 0.05). On all other parameters, there were no significant changes noted between the drugs [Table 3].
Table 3: Comparative efficacy of Yashtimadhu and placebo granules on general health parameters

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Efficacy on intelligence quotient

On comparing the efficacy of trial drug and placebo drug over IQ, the trial drug Yashtimadhu granules provided statistically significant results in improving verbal IQ (P < 0.05) and statistically highly significant results in improving performance and full score IQ (P < 0.0005) [Table 4].
Table 4: Comparative efficacy of Yashtimadhu and placebo granules on intelligence quotient (IQ)

Click here to view


Overall outcome of therapy on intelligence quotient

In Group A, before treatment 42.5% and 57.5% of children belonged to dull IQ (70–89) and average IQ (90–109) category respectively, whereas after treatment 2.5% and 77.5% of children belonged to dull and average IQ category respectively. There were no children with superior IQ (110–124) category before treatment, whereas after treatment 20% of children belonged to superior IQ category [Figure 1].
Figure 1: Overall effect of therapy on intelligent quotient in Group A

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In Group B, before treatment 62.8% and 37.2% of children belonged to dull IQ and average IQ category respectively, whereas after treatment 31.4% and 62.8% of children belonged to dull and average IQ category respectively. There were no children with superior IQ category before treatment, whereas after treatment 5.8% of children belonged to superior IQ category [Figure 2].
Figure 2: Overall effect of therapy on intelligent quotient in Group B

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Evidence-based analysis

The number needed to treat (NNT) to achieve the target of IQ score minimum 90 and above was 3.38, which suggested that 1 out of every 3.38 children who were administered with Yashtimadhu granules achieved IQ score of 90 and above, which was statistically highly significant (P < 0.005). The odd's ratio for achieving this target was 17.88.

The NNT to achieve the target of IQ score minimum 110 and above was 6.66. This suggests that one out of every 6.66 children achieved IQ score of 110 and above after administering Yashtimadhu granules which was statistically insignificant (P > 0.05). The odd's ratio for achieving this target was 4.16 [Table 5].
Table 5: Number need to treat (NNT)

Click here to view



   Discussion Top


Individuals differ from one another in their ability to understand complex ideas, to adapt effectively to the environment, to learn from experience, to engage in various forms of reasoning and to overcome obstacles by their thoughts. Although these individual differences can be substantial, they are never entirely consistent: A given person's intellectual performance will vary in different occasions, and in different domains, as judged by different criteria. Concepts of "intelligence" are attempts to clarify and organize this complex set of phenomena. Although considerable clarity has been achieved in some areas, no such conceptualization has yet answered all the important questions and none commands universal assent.[9]

To assess intelligence level of a child, many factors come into play such as his family background, social background, cultural background, scholastic background, mental status of the child during the testing procedure, environment where the test is conducted, the abilities and disabilities of the child in understanding the commands, etc.[10] Therefore, one such test was necessary that would give an appropriate measure of IQ overcoming all the above differences and variations. By considering all the above factors Indian adaptation of Wechsler's intelligence scale for children – Malin's intelligence scale for Indian children was selected, which has been constructed carefully suiting the standards of Indian children after scientific standardization of samples test items and establishments of the norms.[8]

Medha is understood by Grahana and Dharana Shakti (grasping and retention power), Smriti by Smarana Shakti (recalling power), Dhriti by Aloulyata (absence of distraction) and Vijnana (nature and capacity to perform task alone).[4] Hence, improvement in these functional aspects of Buddhi suggests improvement in the factors analyzed by them.

The factors used to analyze them where IQ test used in the study, which consisted of five verbal and five performance subtests. Verbal IQ tests measured general knowledge, factual knowledge, long-term memory, social – practical judgment, short-term auditory memory, concentration, and numerical reasoning.[8] Whereas performance IQ measured attention power, alertness to visual details and visual discrimination, visual-motor skills, coordination, short-term visual memory, nonverbal intelligence, spatial analysis, graphomotor planning, fine visual-motor coordination.[8]

Based on the entities measured by IQ test and improvement in IQ score, it was understood that improvement in general knowledge, factual knowledge, and numerical reasoning as improvement in Grahana and Dharana Shakti, improvement in long-term memory, short term auditory memory and short term visual memory as improvement in Smriti, improvement in concentration, attention power, alertness to visual details and visual discrimination and fine visual-motor coordination as improvement in Dhriti, improvement in nonverbal intelligence, spatial analysis, graphomotor planning, along with general knowledge, factual knowledge as improvement in Vijnana.

The factors measured by these IQ subtests can be related with assessment of Medha, Smriti, Dhriti and Vijnana mentioned by Acharya Charaka [4] in many ways, hence improvement in these factors was considered as functional increase of Medha, Smriti, Dhriti and Vijnana.

Improvements in physical (P < 0.05) and psychological health (P < 0.001) parameters of World Health Organization-QOL BREF suggest that the trial drug by the virtue of its Balya (promoters of strength), Bruhmana (roborant) and Rasayana Karma (rejuvenation) might have brought in these changes.

The improvement in the parameters of general health parameters can be attributed to the properties of the drug itself.[11]

The mode of action of Yashtimadhu in improving Medha and IQ can be explained through pharmacodynamic properties and chemical constituents present in it. Prabhava (un explainable action) of Yashtimadhu brings about Medhya actions. "Sadindriya Prasadaniya" Karma of Madhura Rasa (sweet taste)[11] present in Yashtimadhu nourishes Manas and Buddhi. Snigdha Guna (unctuous property) Madhura Rasa and Madhura Vipaka properties of Yashtimadhu[11] regulate the Chala Guna (moveable property) of Vata and thereby influence the functions of Manas and Buddhi. Glycyrrhizin is generally regarded as the active principle of G. glabra and is responsible for its sweetness, which is 50 times that of sucrose,[12] it thereby increases the bioavailability of glucose at brain level and thereby enhancing the activity of brain.[13] Presence of flavonoids which are potent antioxidants plays a vital role in preventing oxidative damage to the brain and thereby enhancing the functions of brain.[14] It also possesses acetyl cholinesterase inhibitory activity, which enhances the action and duration of neurotransmitter acetylcholine in central cholinergic pathways, which plays a prominent role in the learning and memory processes.[15]


   Conclusion Top


Intelligence is a vital essentiality in day-to-day life, especially in children. Medha, Smriti, Dhriti and Vijnana can be considered as the functional aspects of Buddhi, and are interrelated with each other and are responsible for acquiring, storing and recalling knowledge. Entities measured by verbal and performance IQ scale had similarity to those mentioned for assessing Medha, Smriti, Dhriti and Vijnana by Acharya Charaka, hence improvement in IQ score suggested improvement in above functional aspects of Buddhi. No adverse reaction was found during the course of study and follow-up. By observing the results obtained, it can be concluded that Yashtimadhu Granules at given dose and duration indeed possesses a significant efficacy in improving Medha (IQ).


   Acknowledgments Top


The authors would like to acknowledge scholars of Dept. of Kaumarabhritya, IPGT and RA, Jamnagar for providing their help during conduction of this study. They are in debt to all those school going children in and around Jamnagar who happily volunteered to be part of this research work. The authors would also like to render their gratitude to Dr. Jyothy K B, Asst. Prof. Dept. of Kaumarabhritya, Mahatma Gandhi Ayurved College, Hospital and Research Centre, Wardha, Maharashtra for her valuable contribution throughout the study.

Financial support and sponsorship

IPGT and RA, Gujarat Ayurved University, Jamnagar, Gujarat, India.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

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Carter P. The Complete Book of Intelligence Tests. The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, England: Published by John Wiley and Sons Ltd.; 2005  Back to cited text no. 2
    
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Acharya YT, editor. Charaka Samhitha of Agnivesha, Sutra Sthana, Ch. 1, Ver. 54. Reprint ed. Varanasi: Chaukamba Orientalia; 2011. p. 14.  Back to cited text no. 3
    
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Acharya YT, editor. Charaka Samhitha of Agnivesha, Vimana Sthana, Ch. 4, Ver 8. Reprint ed. Varanasi: Chaukamba Orientalia; 2011. p. 247.  Back to cited text no. 4
    
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Giurgea C. Pharmacology of integrative activity of the brain. Attempt at nootropic concept in psychopharmacology. Actual Pharmacol (Paris) 1972;25:115-56.  Back to cited text no. 5
    
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Acharya YT, editor. Charaka Samhitha of Agnivesha, Chikitsa Sthana, Ch. 1/3, Ver. 30. Reprint ed. Varanasi: Chaukamba Orientalia; 2011. p. 385.  Back to cited text no. 6
    
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Moorthy KR. Sharangadhara Samhitha of Sharangadhara, Purva Khanda. 6th ed. Varanasi: Chaukhambha Orientalia; 2006. p. 84.  Back to cited text no. 7
    
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Malin AJ. Malin's Intelligence Scale for Indian Children. Agra: National Psychological Corporation; 1969. p. 1-4.  Back to cited text no. 8
    
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Ulrich N, Boodoo G, Bouchard TJ, Wade Boykin A, Brody N, Cecy SJ, et al. Intelligence: Knowns and unknowns. Am Psychol 1996;51:77-101.  Back to cited text no. 9
    
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Shyam R, Khan A. Clinical Child Psychology. Ch. 14. New Delhi: Kalpaz Publication; 2009. p. 276-7.  Back to cited text no. 10
    
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Pandey G. Dravyaguna Vijnana Part II. Varanasi: Chaukambha Krishnadas Acadamy; 2004. p. 462-8.  Back to cited text no. 11
    
12.
Hikino H. Recent research on oriental medicinal plants. In: Wagner H, Hikino H, Farnsworth NR, editors. Economic and Medicinal Plant Research. Vol. 1. London: Academic Press; 1985. p. 53.  Back to cited text no. 12
    
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Gold PE. Role of glucose in regulating the brain and cognition. Am J Clin Nutr 1995;61 Suppl: 987-95.  Back to cited text no. 13
    
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Dhingra D, Parle M, Kulkarni SK. Memory enhancing activity of Glycyrrhiza glabra in mice. J Ethnopharmacol 2004;91:361-5.  Back to cited text no. 14
    
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Pohanka M. Acetylcholinesterase inhibitors: A patent review (2008-present). Expert Opin Ther Pat 2012;22:871-86.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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