Evaluation of Comparative Efficacy of Jyotishmati (Celastrus paniculatus Wild) and Yastimadhu (Glycyrrhiza glabra Linn) in Enhancing IQ and Memory of Different Prakriti School Going Children- A Study Protocol of Double Blind Randomized Clinical Trial

Background: Education plays a major role in life, whereas lack of intelligence, learning, and memory will lead to failure in school performance and school dropout. Medhya drugs are used frequently to enhance the memory and IQ in children. Jyotishmati and Yashtimadhu are medhya Study Protocol Japang et al.; JPRI, 33(52B): 236-244, 2021; Article no.JPRI.76032 237 (IQ-enhancing & memory-booster) drugs, described in numerous classical texts of Ayurveda. However, comparative efficacy and randomized trials on various prakriti types have not been studied. Thus, to assess the comparative efficacy of Jyotishmati in enhancing IQ and memory in relation to Yastimadhu as standard control, this research has been planned. Objective: To evaluate the efficacy of Jyotishmati on IQ and memory, and compare the efficacy with that of Yastimadhu in children with different prakriti types. Methodology: It will be conducted on healthy school-age children of 8-13 years, recruited from CBSE schools near Mahatma Gandhi Ayurved College, Hospital and Research Centre, Salod, Wardha. The study will be a randomized, standard-controlled, double-blind, parallel group clinical study. All participants will be randomly divided into two groups, each of 30 individuals; each group is subdivided into three subgroups of 10 individuals each. One group will be given Jyotishmati while the other will be given Yastimadhu, both in granule form. IQ assessment will be done by using the Draw a Man test and the PGI memory scale for memory assessment. Expected Results: This study will validate the efficacy of Jyotishmati and Yastimadhuin enhancing IQ and memory, and it will give detailed information about their efficacy in different Prakriti dominantchildren. Conclusion: This study will provide unique information to increase awareness of the administration of Medhya drugs according to Prakriti, as well as knowledge about which drug is best for improving either IQ or memory, or both.


INTRODUCTION
The important building stage of a person's career, earning, and life as a whole is education. Poor school performance, early school dropouts, and, eventually, poor economic conditions will result from poor intelligence, learning, and memory issues [1]. There are various interventions and methods available for early diagnosis and treatment to increase the academic performance of such children [2]. Various herbal nootropic agents' use is one of the recent advancements in this field. These nootropic drugs have been proven to be effective in enhancing learning, memory, and cognitive capabilities, and thus are being employed in poor learning and in problems related to memory and low IQ. These nootrophic drugs are Jyotishmati (CelastruspaniculatusWild) and Yastimadhu (Glycyrrhiza glabra, Linn) taken for this study. Yastimadhu was described as Medhya by Acharya Charaka [3],Sushrut [4], and Vagbhat [5], but KaidevNighantu [6],Dhanvantari Nighantu [7], Raj Nighantu [8], and Bhavaprakash Nighantu [9] specifically mentioned Jyotishmati as Medhyadravyas.
Recently, in animal studies, it has been proven that the enhancing cognition action as well as the memory function of Jyotishmati [10] and Yastimadhu [11]. There are no conclusive randomised clinical trials to validate their medhya efficacy as per prakriti in children. These herbal nootropic medhya drugs are widely used without proper consideration of Ayurveda principles, which could lead to misuse. One of the important Ayurvedic principles is the assessment of Prakriti, and drugs should be used according to Prakriti types. Due to the high demand for nootropic drugs, they are randomly used without proper analysis of the prakriti of a person and, hence, may not achieve the optimum efficacy desired. Ideally, we need to prescribe herbs as per Prakriti and other principles to augment the efficacy. This study will address the rational use of Prakriti-based nootropic drugs by enhancing their action and outcome. Using Jyotishmati and Yastimadhu as examples, we did not find any research work done on a prakriti basis to evaluate the association between memory and IQ. Thus, to assess the comparative efficacy of Jyotishmati in enhancing IQ and memory in relation to Yastimadhuas a standard control, this research has been planned.

Need for Study
Intelligence and memory have a close relationship and both play an important role in various developmental areas during childhood, but till date these have not been compared in a single study. Those who have good intelligence and memory are more successful in school, work and social life [12]. Thus, IQ and memory are important factors in day-to-day life. Various research has been done on different Medhya drugs for enhancing IQ and memory separately. But no research has been found on correlative study of Jyotishmati and Yastimadhu based on Prakriti in children. Thus, this study has been planned to understand the IQ and memory correlation of a child, based on their Prakriti dominant.

Research Gap Analysis
Jyotishmati and Yastimadhu are both described as Medhyadravyas in classical text. However, no study till date has been done to compare IQ and memory together in children with different Prakritis. As in Ayurveda it has told that Bhaisaja(drug) should be given by proper assess of prakriti, desha, kala etc. Thus, this study will establish the effect of medhya drugs (Jyotishmati&Yastimadhu) and estimate the effect equivalence of these two drugs.

Research Question
Whether Jyotishmati is as efficacious as Yastimadhu in enhancing IQ and memory in children of different Prakriti?

Review of Literature
In Ayurveda compendia, there are many scattered references of Dhee (Buddhi), Dhruti (grasping) and smruti (memory)as well as role of Medhya rasayan in augmenting its function. The literary review on these aspects related to IQ, memory and both the drugs is compiled in the Table 1.

Source of data/ Place of Study
Healthy volunteer children recruited from CBSE schools near Mahatma Gandhi Ayurved College, Hospital and Research centre, Salod, Wardha.
Study types: Interventional study.

Study Design
Randomized, standard controlled, double blind, parallel group clinical trial.
The study will be randomized, standard controlled double blind, parallel group clinical study on healthy volunteer children between 8-13 years.

Drug Collection/Authentication
Raw materials required for the preparation of Jyotishmati granules and Yastimadhu granules will be procured from Dattatrayarasashala and organic jaggery and cow ghee will be taken from (AGMARK certified company).It will be authenticated by Department of Dravyaguna, MGACH&RC, salod(H).

Method of Preparation
Thecommon method of granules preparation is as follows; 2 parts of jaggery is heated in a vessel till it melted.
Add 1 part of (Jyotishmati,Yastimadhu) fine powder and heat until it become mass Add 1/10 of cow ghee to the mass The mass is kept in granulating machine to get the granules The granules are kept in drying machine to dry Thus, formed granules will be sealed and packed in container.

Sampling Techniques
Equal number of participants (Gender,Age,Prakriti)will be kept in each group.
Randomize through table of random number or computer-generated random allocations software method to avoid bias.

Sample Size
The sample size is calculated according to the effect size from the previous study [13]. For this study we are using by the following formula:

Formula:
• Fixed Scenario Elements

Distribution into Groups
The children with dominant dwidoshajPrakriti will be divided into two groups(A and B). Each group has three sub-divided group with three dominant Prakritii.eVatapitta, Pittakapha, Kaphavata.Out of which, Group B will be given JyotishmatigranulesandGroupA will be administered Yastimadhu granules as standard control. Each group will be having 30 participants, 10 in each subdivided group.Thus, whole study is planned upon a total 60 healthy school age children.

Intervention
Group B will be given Jyotishmati granules while Group Y is given Yastimadhu granules both with milk in dose as per age in two divided dose. Granules will be made of study drug i.eYastimadhu and Jyotishmati, with use of jaggery and cow ghee. The drug will be given continuously for 60 days.

Withdrawal Criteria
 If children or parents later didnotwant to completethe study.  Anyillness that required hospitalization.  Any severe adverse drug events.

Adherence Monitoring
The participants will be adhering to the study drugs and will be assessed by monthly follow-up and telephonic communications as well as assessment of drugs use at follow up through return of empty containers.

Jyotishmati
(CelastruspaniculatusWild) and Yastimadhu (GlycyrrhizaglabraLinn) are both described as MedhyaRasayana in ancient classics of Ayurveda. They are being used since ages for their nootrophic action. The Table no 3 indicates their properties.

Assessment
Prakriti Assessment [16]  Prakriti of all the participants will be assessed before registering for the study.
 Prakriti will assess through "PrakritiVichaya" module of AyuSoft software of Centre for Development of Advanced Computing (C-DAC).  The module possesses variousquestionnaire specific to age group and gender.  It covers history, physiological & psychological, anatomical, assessment with practical options to each question.

Memory Assessment:
Memory will be assessingby "PGI MEMORY SCALE FOR CHILDREN" [17]. It consists of ten subtests,they are-remote memory, recent memory, mental balance, attention and concentration, delayed recall, immediate recall, verbal retention for similar pairs, verbal retention for dissimilar pairs, visual retention, recognition of common objects.
The main domain assessed will be: • Working memory (immediate).
• Short term memory.
• Long term memory.

IQ assessment:
Draw-A-Man-Test [18]: • The children will be given paper and pencil to draw a man according to their knowledge. • The score is giving base on different body parts like eyes, nose, hand etc.

Statistical Analysis
Assessment parameters will be subjected to Univariate and multivariate analysis using SPSS 21.0 VER with appropriate statistical methods.
• The data will be analyzed by using paired t-test & unpaired t-test for objective parameters and Mann-Whitney U test, Wilcoxon rank-sum test, one/two-way ANOVA tests for subjective parameters. • Test of hypothesis superiority analysis will be done through the application of appropriate inferential statistics.

Safety Recording
Adverse Drug Events: All adverse events with information of severity and any related to the study medication will be recorded. If there is serious adverse effect then immediately it will be notified to the study monitor.

Study Schedule
Study requires Prakriti assessment first which is going to be foremost task and will be assessed once only, as it remains same till lifelong but IQ and memory will be evaluated pre and post of the study to confirm the efficacy of both the drugs in the respective groups. Study schedule of the research trial is mentioned in the Table 4.

Allocation & Blinding
The participants in both the group will be allocated randomly by computer generated random allocation software. In advance, the location sequences will be generated, and consecutively numbers sealed in opaque enveloped. By keeping both the interventions packing identical, the investigator and supervisor could not know about the interventions. Investigator (MD scholar) and supervisor will generate the allocation sequence and enroll participants as well and intervention will assign to them. This study is double blind, so after the assignment of intervention both the investigator & participants will be blinded.

Observation and Result
Data obtained from the follow up chart and other observations and the results will be drawn on the basis of various charts, graphs, and tables.

Expected Outcomes/Results
Through this study detail information about the efficacy of Jyotishmati and Yastimadhu in different prakriti children will be given. It will also demonstrate Ayurvedic concepts regarding IQ and memory of different types of prakriti. Jyotishmati has been shown to be highly significant in improving neuronal function (Bhagya. V, 2020) [19]. and has shown highly significant backward digit span in one study (Dhodapkar SP, 2018) [20]. In another study, it has shown improvements in cognitive deficits (Srinibash.s, 2018) [21]. While Yastimadhu has shown high significance in improving the functional aspects of buddhi and IQ (Sriharisheshagiri, 2015) [22] in another study

CONCLUSION
There are a lot of requirements to enhance awareness of Ayurvedic Medhya drugs in prakriti-based administration of drugs. The study will provide accurate information, particularly in this part. For the sake of societal benefit, both of these medhya drugs will be utilised to their optimum effect.

SCOPE OF THE STUDY
It will be first comparative study on JyotishmatiandYastimadhu. The result of the study will help practitioner in rationale use of both these drugs. According to the Prakriti of patient, it will further open the doors for new studies on various Medhya drugs to evaluate their differential effects on various types of Prakriti. After giving detail account of plan and objectives of the study, the written informed consent from the parents of the participants will be taken. Whatever findings in this study, articles will be published to display the result for the benefit of not only medical practitioners but also the whole society.

DISCLAIMER
The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors.

RESEARCH SIGNIFICANCE
The study highlights the efficacy of "Ayurved" which is an ancient tradition, used in some parts of India. This ancient concept should be carefully evaluated in the light of modern medical science and can be utilized partially if found suitable.