1) Introduction

F1000Research

2046-1402

F1000 Research Limited

London, UK

10.12688/f1000research.160416.2

Research Article

Articles

Ginkgo Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus database. A bibliometric study from 1988 to 2024

[version 2; peer review: 1 approved, 1 approved with reservations]

SALEH

ARMAN YURISALDI

Conceptualization Data Curation Formal Analysis Funding Acquisition Investigation Methodology Project Administration Resources Software Supervision Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0001-5866-3585 a 1 Saputra

Dwi Arwandi Yogi

Writing – Original Draft Preparation Writing – Review & Editing 2 Valentina

Riezky

Writing – Review & Editing 1 Susanto

Tirta Darmawan

Writing – Review & Editing https://orcid.org/0000-0002-4151-5946 3 1Neurology Department Faculty of Medicine, Universitas Pembangunan Nasional (UPN) Veteran Jakarta, Jakarta, Special Capital Region of Jakarta, 12450, Indonesia 2Department of Public Health Sciences, Faculty of Medicine, Universitas Pembangunan Nasional (UPN) Veteran Jakarta, Jakarta, Special Capital Region of Jakarta, Indonesia 3Family Medicine and Primary Care Department, Universitas Pelita Harapan, Tangerang, Banten, 15811, Indonesia

a drarmanyurisaldic@gmail.com

No competing interests were disclosed.

15 5 2025

2025

275

12 5 2025

2025

This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1) Introduction

Cognitive enhancers, also known as nootropics, aim to improve cognitive functions, such as memory and attention. Despite their potential benefits, the challenges include scientific validation, ethical considerations, and regulatory hurdles. This bibliometric study analyzes literature from Scopus to identify key trends, influential authors, and research gaps, providing guidance for future research.

2) Methods

This study employs a literature review methodology to gather data from the Scopus database on Neuroaid, analyzing it using Biblioshiny and VOSviewer software. The focus was on Ginkgo Biloba as a niche-theme cognitive enhancer agent based on Scopus data, using both quantitative and qualitative analyses.

3) Results and discussion

Ginkgo biloba, the 'maidenhair tree’ from the order Ginkgoales, appeared 290 million years ago. Chinese and Japanese culture has been cultivated for thousands of years. This tree is valued for its resilience and therapeutic properties, often used in traditional medicine for respiratory and blood circulation issues.

4) Conclusions

This bibliometric study on cognitive enhancers aims to provide a comprehensive and systematic review of the existing literature, highlighting key trends, influential authors, and research gaps. The findings of this study will contribute to a better understanding of the current state of research on cognitive enhancers and inform future research. This study was conducted in December 2024.

Cognitive enhancer agent ginkgo biloba niche

The author(s) declared that no grants were involved in supporting this work.

Revised Amendments from Version 1

Major Revisions Required to be Scientifically Sound 1. Clarify and document the search methodology in full detail to ensure reproducibility. 2. Provide access to the raw Scopus data exports and search strings. Justify the absence of filters or explain how the lack of filtering does not compromise data validity. 3. Avoid merging clinical conclusions with bibliometric findings unless systematically substantiated. 4. Improve citation consistency and integrate references more clearly throughout the discussion. Peer Review : 1. We have revised the manuscript according to the reviewer's request and have also submitted the new version of the manuscript. 2. All data we used in the study have been uploaded to The article references an extended dataset on Figshare : https://doi.org/10.6084/m9.figshare.28081709.v1 and can be accessed publicly 3. We have revised the manuscript according to the reviewer's request and have also submitted the new version of the manuscript. 4. All citations are in Table 1 Qualitative analysis of the research summary of each abstract that has been uploaded is also in Figshare : https://doi.org/10.6084/m9.figshare.28081709.v1 and can be accessed publicly

Introduction

Cognitive enhancers, also known as nootropics or smart drugs, have garnered significant attention from both the scientific community and popular culture. These substances are designed to improve cognitive functions, such as memory, attention, and problem-solving abilities in both healthy individuals and those experiencing cognitive decline. ¹ The growing interest in cognitive enhancers is driven by their potential benefits in enhancing mental performance, which can be particularly valuable in competitive environments such as academia and the workplace. ²

Despite the promising potential of cognitive enhancers, this field faces several challenges, including the need for rigorous scientific validation, ethical considerations, and regulatory hurdles. ³ The current body of literature on cognitive enhancers is vast and diverse, encompassing studies on various pharmacological agents, non-pharmacological interventions, and their effects on different cognitive domains. ⁴ However, there is a lack of a comprehensive bibliometric analysis that systematically reviews and synthesizes this body of research.

This bibliometric study aimed to fill this gap by providing a comprehensive analysis of the existing literature on cognitive enhancers indexed in Scopus. By employing bibliometric methods, this study identified key trends, influential authors, and research gaps in the field. The findings of this study will contribute to a better understanding of the current state of research on cognitive enhancers and inform future research.

The methodology of this study involved the collection and analysis of data from Scopus, focusing on articles published between 1988 and 2024. The data will be analyzed using various bibliometric techniques, including co-citation, keyword, and network analyses. The results are presented in the form of visualizations and descriptive statistics, providing a clear and comprehensive overview of the research landscape.

The significance of this study lies in its potential to inform policy decisions, guide research funding and shape the development of cognitive enhancers. By identifying the most impactful studies and emerging trends, this bibliometric analysis will help researchers and policymakers prioritize areas of research that are likely to yield the greatest benefits.

Methods Bibliometric research approach

Bibliometric research employs structured analysis of scientific publishing data to map the evolution of specific disciplines. This study focuses on the topic of cognitive enhancers, aiming to identify trends, patterns, and correlations within academic literature. To ensure transparency and reproducibility, we systematically documented the data collection, search strategy, and analytical procedures.

Data source and search strategy

This study utilized Scopus ( www.scopus.com), a widely recognized and reputable database for scientific literature. The search was conducted in December 2024 using the following parameters: •

Search Keywords: “cognitive enhancer”

•

Search Fields: Title, Abstract, Keywords (TITLE-ABS-KEY)

To ensure comprehensive coverage, no additional filters (such as publication year, language, or document type) were applied. The decision to maintain an unfiltered search was based on the goal of retrieving all relevant publications without introducing potential bias in the selection process.

Data retrieval and export formats

The retrieved results were exported from Scopus in three distinct formats for bibliometric analysis: 1.

CSV (Comma-Separated Values): Provides metadata, including title, authors, affiliations, publication year, source, abstract, and keywords.

RIS (Research Information System): Contains detailed bibliographic records, including citation data.

TXT (Plain Text): Includes structural elements necessary for further processing in Biblioshiny and VOSviewer.

Data collection and processing

A search query was executed using “cognitive enhancer” in the TITLE-ABS-KEY field. This resulted in the retrieval of 1414 relevant documents. These documents were exported and stored in .csv format for further bibliometric analysis. The exported data was then processed using Biblioshiny and VOSviewer, which enabled visualization of research trends, co-authorship networks, and keyword clustering.

Ensuring reproducibility

To enhance reproducibility: •

The search query string (TITLE-ABS-KEY (“cognitive enhancer”)) and data export settings have been clearly documented.

•

No additional filters were applied, and justification for this approach is explicitly stated.

•

The raw Scopus data exports will be made available upon request to facilitate independent verification.

Data analysis

Both the Biblioshiny and Vosviewer software packages were utilised in the analysis process.

Quantitative analysis

Documents by Year.

Figure 1 indicates an increase in the number of documents, culminating in 61 papers by 2023. The earliest document dates back to 1988 and comprises two papers titled "Antagonism by Exifone, a New Cognitive Enhancing Agent, of the Amnesias Induced by Four Benzodiazepines in Mice," authored by Porsolt, R.D., Lenègre, A., Avril, I., and Doumont, G. The second document, headed "Comparison of the Effects of Vinpocetine, Vincamine, and Nicergoline on the Normal and Hypoxia-Damaged Learning Process in Spontaneously Hypertensive Rats," is authored by Groó, D., Pálosi, É., and Szporny, L. As of 2024, there are 54 documents, with the most recent titled "MSK 1," which is essential for the experience- and ampakine-dependent strengthening of spatial reference memory and reversal learning, as well as for the induction of Arc and BDNF written by Morè et al. ⁷

Figure 1. Documents by year. Figure 2. Most Relevant Sources.

Most Relevant Sources

According to Figure 2, Neuropharmacology occupies the foremost position. This contains information regarding the journal neuropharmacology. The journal has been indexed in Scopus since 1962. The current SCImago Journal Rank (SJR) for this journal was 1.307. It was published by Elsevier Ltd. The journal publishes high-quality original research in neuroscience, concentrating on the examination and comprehension of the effects of exogenous and endogenous chemical agents on neurobiological processes in the mammalian nervous system. This journal is classified as Q1 in the fields of cellular and molecular neuroscience, and pharmacology. Psychopharmacology has been indexed in Scopus since 1959. The most recent SJR is 1.053. SCImago quartile classification, Q1 (highest). This magazine accepts many manuscripts, including experimental studies on the impact of medications on human cognition and behavior as well as laboratory investigations involving experimental animals. It also invites works that incorporate various levels of analysis, ranging from neurochemical assays to functional neuroimaging research. Ranking three is the Journal of Behavioral Brain Research. This contains information regarding the Journal of Behavioral Brain Research. This journal has been indexed in Scopus since the 1980. The most recent data indicate that the SCImago Journal Rank (SJR) for Behavioral Brain Research is 0.881. This study was published by Elsevier B.V. This magazine welcomes diverse forms of submission, encompassing original research, methodological innovations, and critical analyses within the domains of neuroscience, behavioral science, and cognitive science. This journal is classified as Q2.

Figure 3. Most Global Cited Documents.

Most Global Cited Documents

According to Figure 3, the most cited document, with 1059 citations, is the journal titled Identification of separable cognitive factors in schizophrenia, authored by Keith H. Nuechterlein, Deanna M. Barch, James M. Gold, Terry E. Goldberg, Michael F. Green, and Robert K. Heaton. The journal's abstract states that one of the main objectives of this research was to identify separate cognitive factors in schizophrenia. This study aimed to better understand how this disorder affects various cognitive aspects, such as memory ability, attention, and information processing.

Second, with 946 citations, a document titled "Cognitive Enhancers as Adjuncts to Psychotherapy: Use of D-Cycloserine in Phobic Individuals to Facilitate Extinction of Fear" was authored by Kerry J. Ressler, MD, PhD; Barbara O. Rothbaum, PhD; Libby Tannenbaum, PhD; and colleagues. Background: This study evaluated the use of D-cycloserine (DCS), a partial agonist of N-methyl-D-aspartate (NMDA) receptors, as an adjunct to exposure therapy for individuals with phobias. Previous studies have demonstrated that DCS can accelerate fear extinction in animals.

The third-ranked document, with 623 citations, is titled Ionotropic and Metabotropic Glutamate Receptor Structure and Pharmacology. This review was published on February 25, 2005, in Psychopharmacology. The authors of this review were James N. C. Kew and John A. Kemp. This document discusses ionotropic and metabotropic glutamate receptors, which are two major receptors that function as primary excitatory neurotransmitters in the central nervous system (CNS).

Factorial Map Of The Documents With The Highest Contributes

In Figure 4, the most contributed manuscript, titled “D-Cycloserine Augmentation of Exposure Therapy for Post-Traumatic Stress Disorder: A Pilot Randomized Clinical Trial” by JoAnn Difede, was published in Neuropsychopharmacology. The study was accepted on November 12, 2013, and published online on December 11, 2013.

Figure 4. Factorial map of the documents with the highest contributes.

This study discusses the use of D-cycloserine (DCS) to enhance the effectiveness of virtual reality exposure (VRE) therapy in patients with PTSD. The main goal was to determine whether DCS could improve psychotherapeutic effectiveness by accelerating the process of extinguishing fear and increasing neuroplasticity (the brain's ability to adapt and change).

Documents by Author

According to Figure 5, the three most prolific authors, each with 16 documents, are as follows: Sahakian, B.J., with many paper titles: Enhancement of the motor control network with methylphenidate in individuals with traumatic brain injury. Effects of atomoxetine on attentional bias towards drug-related signals in cocaine-dependent individuals Modafinil Enhances Episodic and Working Memory Cognition in Patients with Remitted Depression: A Double-Blind, Randomized, Placebo-Controlled Study. Examining the Neuroscience and Societal Consequences of Cognitive Enhancers as well as the utilization of substances by healthy individuals to augment cognition, creativity, motivation, and enjoyment. ^{8–
12}

Figure 5. Documents by Author.

The subsequent author with 14 publications is Steiner, H., whose articles include: Methylphenidate with or without fluoxetine triggers the restoration of cocaine-seeking behavior in rats. Vilazodone, an innovative SSRI antidepressant with 5-HT1A partial agonist characteristics, reduced the potentiation of chronic oral methylphenidate-induced dynorphin expression in the striatum of male adolescent rats. Fluoxetine amplifies the behavioral effects generated by methylphenidate: increased locomotion or stereotypies, and improved acquisition of cocaine self-administration. Concurrent Chronic Administration of Oral Methylphenidate and Fluoxetine During Adolescence: Behavioral Effects, and Fluoxetine Enhances Oral Methylphenidate-Induced Gene Regulation in the Rat Striatum. ^{13–
17}

The subsequent author with 14 publications is Wattanathorn, J., whose articles include: Effect of Single Administration of Mulberry Milk on the Cognitive Function of 6-12-Year-Old Children: Results from a Randomized, Placebo-Controlled, Crossover Study. Assessment of the neuroprotective and cognitive enhancement properties of Cucurbita moschata. Mung bean-derived protein protects against neurodegeneration and memory deficits in an animal model of menopause with obesity. The amalgamated extract of black sticky rice and dill enhances cognitive deficits following stroke in individuals with metabolic syndrome and functional beverages. A novel cognitive enhancer, comprising extracts of purple corn cob and pandan leaves, enhances spatial memory and hippocampal neuron density by improving extracellular signal-regulated protein kinase expression, cholinergic function, and oxidative status in ovariectomized rats. ^{18–
22}

Documents by country or territory

Figure 6 indicates that the United States has the highest number of document creators, totaling 436 documents. The United Kingdom followed 206 documents, followed by Japan with 95. Germany possesses 90 documents, whereas Canada has 87.

Figure 6. Documents by country or territory.

Documents by Subject Area

Figure 7 shows a pie chart depicting the distribution of the documents by subject area. The graph shows the percentage of documents classified into different subject areas. The percentage details for each topic area were as follows: medicine: 25.2% or 614 documents. Neuroscience: 21.3% (518 documents) Pharmacology, Toxicology, and Pharmaceutics: 21.1% (513 documents) Biochemistry, Genetics, and Molecular Biology: 11.5% (280 documents) Psychology: 6.3% or 280 documents. Social Sciences: 2.7% or 65 documents. Chemistry: 2.6% or 64 documents. Nursing: 1.9% or 47 documents. Multidisciplinary: 1.8% or 44 documents. Agricultural and Biological Sciences: 1.7% or 41 documents, which is noteworthy as it illustrates the substantial dispersion of documents across several topic areas, with medicine comprising the largest percentage. It is crucial to comprehend the study or publication emphasis in various fields.

Figure 7. Documents by Subject Area.

Documents by affiliation

According to Figure 8, in first place, the producer of most documents is affiliated with the University of Cambridge with 33 documents, the second is affiliated with the University of Cambridge with 31 documents, and the Boston University with 21 documents.

Figure 8. Documents by affiliation.

Documents by funding sponsor

Referring to Figure 9, the sponsors that generate the highest number of documents for funding are the National Institutes of Health with 111 documents, followed by the National Institute of Mental Health with 68 documents, and the U.S. Department of Health and Human Services producing 67 documents.

Figure 9. Documents by funding sponsor. Figure 10. Network Visualization.

Network Visualization

Figure 10 indicates that the examined areas remained unassociated with the other regions delineated by the edges. The domain encompasses agitation, anorexia, vomiting, caregiver, tremor, hypertension, dietary supplement, Ginkgo biloba extract, huperzine A, anti-inflammatory activity, oxidative stress, glutathione, malondialdehyde, plant extracts, chemical structure, drug synthesis, peptide fragment, amyloid beta-protein, ^{1–
42} in vitro studies, peptide fragments, protein, phosphorylation, calpain, animal, cell, nerve cell, phosphorylation, brain nerve cell, compounds, water maze, NMDA receptor 1, hippocampal CA1 region, BDNF, swimming, Morris water maze, reference memory, cues, choice behavior, mental recall, volunteer, normal human, crossover, procedure, double-blind method, randomized controlled trial, adolescent, impulsive behavior, phobia, substance-related disorders, clinical article, ethics, outcome assessment, universities, students, and students.

Overlay Visualization of Scopus, Database Using Vosviewer

According to Figure 11, in the overlay visualization, it appears that the keywords that are being researched a lot approaching 2016 are the parts colored yellow, namely gluthahione, malonaldehyde, metabolism, prescription, major clinical study, randomized controlled trial (t, addiction, student, students, universities, oxidative stress, chemistry, and nerve degeneration.

Figure 11. Overlay visualization of scopus, database using Vosviewer.

Density Visualization

This is illustrated in Figure 12, in the visual circulation density, it appears that the part that is already saturated with research is yellow, while the part that is not yet saturated is slightly yellow and dominantly green, namely keywords: agitation, vomiting, anorexia, ginkgo biloba extract, cholinesterase, oxidative stress, glutathione, malonaldehyde, galantamine, pain, dementia, tacrine, nerve degeneration, plant extracts, sertraline, tremor, hypertension, neuroprotection, choline, degenerative disease, trazodone, side effect, antipsychotics, pathogenesis, alzheimer disease, cholinesterase inhibitors, dietary supplements, piracetam, drug penetration, drug structure, randomized controlled trial (t, drug safety, amfebutamone, prazosin, protein phosphorylation, peptide fragments, prevalence, olanzapine, neuroleptic agent, anxiolytic agent, ritanserin, memory disorder, amyloid beta protein[1-42], psychotic disorders, prescription, reboxetine, clinical trial, guanfacine, drug synthesis, chemistry, molecular structure, drug structure, in vitro study, peptide fragments, treatment outcome, narcolepsy, cell count, spiro compounds, ethics, placebo, outcome assessment, central stimulant agent, drug abuse, stress, universities, major clinical study, middle aged, substance-related disorders, clinical article, adolescent, phobia, impulsive therapy, motivation, attention, adult, addiction, fear, reinforcement, recall, accuracy, normal human, volunteer, randomized controlled trial, double-blind method, crossover procedure, mental recall, choice behavior, brain function, dopamine, task performance, reaction time, conditioning, operant, frontal cortex, genotype, mental recall, choice behavior, facilitation, nmda receptor, bdnf, ca1 region, hippocampal, mice, inbred c57bl, injections, intraperitoneal, animal behavior, behavior, animal, analysis of variance, striatum, exploratory behavior, morris water maze, reference memory, swimming, water maze.

Figure 12. Density visualization.

Thematic Map

According to Figure 13, on the thematic map based on the title, the following is an explanation for each keyword in each quadrant in the thematic map resulting from the bibliometric analysis. Here is an explanation of the meaning of each quadrant in the thematic map, and examples of document titles relevant to keywords in each quadrant.

Figure 13. Thematic map.

Niche Themes (Upper-Left Quadrant):

Keywords: Biloba, ginkgo, formation. Niche themes are well-developed topics that are not central to the overall research field. This means that, although this research is important, it is not currently the main focus. Example Document Titles: Neuroprotective effects of Ginkgo biloba in Alzheimer's disease. Ginkgo biloba extract and cognitive function: A review of the literature. Formation of cognitive enhancers from natural sources: The case of Ginkgo biloba.

.Motor Themes (Upper-Right Quadrant): Keywords: receptor, brain, rat, effects, memory, rat. Meaning: Motor themes are well-developed and central to research. This means that these themes are important and the main focus of the research. Example document titles: Role of NMDA receptors in brain function and cognition. Effects of novel cognitive enhancers on memory formation in rats. Effect of receptor modulators on cognitive enhancement in animal models.

Basic Themes (Lower-Right Quadrant):

Keywords: cognitive, enhancer, enhancer. Meaning: Basic themes are fundamental topics central to the field of research but are not yet well-developed. These are the foundations from which more specialized research can be developed. Example Document Titles: Overview of cognitive enhancers: mechanisms and applications. Cognitive enhancers: A review of their efficacy and safety. Evolution of cognitive enhancer research: From theory to practice.

Emerging or Declining Themes (Lower-Left Quadrant):

Keywords: study, patients, disorder, cognitive enhancers, enhancer. Meaning: Emerging and declining themes are topics that are either newly developing or losing relevance. This means that these are new areas being developed or possibly declining, if no significant new findings are made. Example Document Titles: Clinical studies of cognitive enhancers in patients with cognitive disorders. Role of cognitive enhancers in the management of cognitive disorders. Emerging trends in cognitive enhancer research: a clinical perspective.

Thematic Evolution

According to Figure 14, there was an evolution of changes in themes in research from 1988 to 2014 with the keywords cognitive, disease, receptor, effects, and memory. The theme then changed in 2015–2024 to effects, disease, study, cognition, and review.

Figure 14. Thematic Evolution.

Topic Dendogram

According to Figure 15, there are 2 large clusters According to keywords. There are 2 clusters of blue and red.

Figure 15. Dendogram.

Qualitative Analysis - refer to extended data for table 1 ¹⁴²⁰

Results and Discussion

Ginkgo biloba, also known as the maidenhair tree, is a living species of the order Ginkgoales, which first appeared over 290 million years ago. This plant has been known and developed by Chinese and Japanese cultures for thousands of years, and is often planted in temple gardens. ¹⁴¹⁵ This tree is valued not only for its resilience, but also for its therapeutic properties, which have been utilized in traditional medicine for centuries. In ancient China, Ginkgo biloba leaves have been used in medicinal practices to address respiratory disorders and improve blood circulation. ¹⁴¹⁶

The use of G. biloba as medicine has been documented in various ancient medical texts. In traditional Chinese medicine, ginkgo leaves are often made into tea or liquid extracts for use as a tonic to improve blood flow and address digestive and respiratory issues. Over time, the use of G. biloba has spread to various cultures worldwide, including Japan and Korea, where it continues to be valued for its health benefits. ¹⁴¹⁷

With advancements in pharmaceutical technology, G. biloba extracts have been formulated more efficiently to maximize their therapeutic benefits. The most commonly known standardized extract is EGb 761, which contains 24% flavonoid glycosides and 6% terpenoids. This formulation ensures consistency and product quality. The extract is used in various supplements including tablets, capsules, and liquids. ¹⁴¹⁸

The usual dosage for G. biloba supplements is 40 mg three times a day or 80 mg twice a day, with a maximum dose not exceeding 240 mg/day. This dosage is based on research showing the effectiveness and safety of these doses in improving cognitive function and reducing the symptoms associated with cognitive disorders. Studies have also indicated that proper dosing can have significant effects without causing harmful side effects. ¹⁴¹⁹

Ginkgo biloba has various complex mechanisms. One of the primary mechanisms is the enhancement of blood flow, especially to the brain, through its vasodilator effect. This helps improve oxygenation and nutrient delivery to brain cells, which in turn can enhance cognitive function. Additionally, G. biloba contains flavonoids and terpenoids with antioxidant properties, which help protect brain cells from oxidative damage caused by free radicals.

In addition to enhancing blood flow, flavonoids in G. biloba also have strong antioxidant effects. These antioxidants scavenge free radicals, which can damage cells and tissues in the body. On the other hand, terpenoids have anti-inflammatory properties that help reduce inflammation, which can cause tissue damage and cognitive disorders. The combination of antioxidant and anti-inflammatory effects makes G. biloba an effective therapeutic agent for protecting and improving brain function.

In the modern era, G. biloba has become the subject of various clinical studies investigating its effectiveness in various health conditions. One of the most prominent areas of research is its use in the treatment of dementia and mild cognitive impairment. Studies have shown that G. biloba extract can help improve memory, attention, and overall cognitive function in individuals with mild-to-moderate cognitive impairment.

Although G. biloba is generally considered safe, some side effects have been reported, including headache, dizziness, digestive issues, and allergic reactions. Therefore, it is important to follow the recommended dosage and consult with a healthcare professional before starting Ginkgo biloba supplements, especially for individuals who are taking other medications or have certain health conditions.

Some Ginkgo biloba products available on the market include Cereton, Cerviboost, Gingkan, Ginkgo Biloba Capsule, and GNC Ginkgo Biloba Plus. These products are available in various forms including tablets, capsules, and syrups. Each product typically lists the standardized content of G. biloba extract, making it easier for consumers to choose according to their needs. ¹⁴¹⁹

Many clinical trials have investigated the effectiveness of G. biloba in various health conditions. These studies included diverse populations, including healthy individuals, patients with dementia, and individuals with mild cognitive impairment. Clinical trials have shown that G. biloba can help improve cognitive function and memory, as well as reduce symptoms of dementia and other cognitive disorders. Dosage standardization of G. biloba has also been carried out to ensure consistency and safety during its use.

Further research has shown that G. biloba can affect neurotransmitters in the brain. For instance, G. biloba extract has been found to increase serotonin and dopamine levels, which play key roles in mood regulation and cognitive function. This indicates that in addition to its vasodilator and antioxidant effects, G. biloba can also influence biochemical pathways in the brain that contribute to improved cognitive function.

Research has shown that G. biloba can provide significant benefits in high-risk populations, such as the elderly and individuals with a genetic predisposition to cognitive disorders. In these populations, the use of G. biloba has been associated with a slower rate of cognitive decline and an overall improvement in quality of life. This underscores the potential of G. biloba as an effective preventive intervention. ¹⁴¹⁵

To ensure the quality and safety of G. biloba products, strict regulations have been established in many countries. Marketed products must meet specific standards regarding the content and purity of the G. biloba extract. This includes standards for the concentration of flavonoid glycosides and terpenoids as well as testing for contaminants that may be present in the final product. ¹⁴¹⁷

Additionally, comparative studies between G. biloba and other cognitive agents, such as donepezil and memantine, have been conducted. These studies aimed to determine the relative effectiveness of G. biloba compared with more commonly used medications in the treatment of dementia and cognitive disorders. The results of these studies indicated that G. biloba has a unique benefit and risk profile, making it an attractive option for use in combination with other therapies.

Although many studies have shown the benefits of G. biloba, there are still challenges in terms of the research methodology and variability of results. Further research is needed to understand the precise mechanisms of action and to determine the optimal dosage for various populations and health conditions. Further efforts are required to enhance the regulation and standardization of Ginkgo biloba products in the global market.

Conclusions

This bibliometric study highlights the increasing scientific interest in Ginkgo biloba as a cognitive enhancer, demonstrating a steady rise in research outputs from 1988 to 2024. By mapping publication trends, influential studies, and keyword clusters, the analysis provides valuable insights into the scope and trajectory of research in this domain.

While Ginkgo biloba has been widely studied for its vasodilatory, antioxidant, and neuroprotective properties, bibliometric findings do not independently verify clinical effectiveness. The literature suggests promising therapeutic potential, particularly in memory enhancement and neurodegenerative disorders, but methodological inconsistencies in clinical trials underscore the need for standardized research protocols and larger sample sizes.

This study also identifies gaps in comparative research between Ginkgo biloba and established pharmacological treatments such as donepezil and memantine, calling for further investigations to clarify efficacy, safety, and optimal dosing strategies. Additionally, regulatory frameworks remain crucial in ensuring quality control and product standardization across global markets.

Future research should focus on refining experimental designs, integrating systematic clinical trials and conducting long-term safety assessments. By maintaining a clear distinction between bibliometric trends and clinical claims, this study serves as a foundation for guiding future investigations into the cognitive-enhancing potential of Ginkgo biloba.

Ethics and consent

Ethical approval and consent were not required.

Reporting guidelines

Figshare: PRISMA-ScR checklist and flow chart: Gingko Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus data Base. A bibliometric studi from 1988 to 2024,

DOI: 10.6084/m9.figshare.28081724 ( https://doi.org/10.6084/m9.figshare.28081724.v1) ¹⁴²⁰

The project contains the following reporting guidelines: •

PRISMA_2020_checklist_AYS

•

PRISMA_2020_flow_diagram_new_AYS

The data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Software availability

VOSviewer software is an open-access tool that can be used as a cost-effective method for scientometric analysis Biblioshiny

Author contribution

AYS conducted research, gathered data, performed statistical analysis, and produced discussions and conclusions, including TDS, RV, and DAYS editing.

Data availability statement

No Data Associated with this manuscript.

Extended data

Figshare: Gingko Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus data Base. A bibliometric studi from 1988 to 2024

DOI: 10.6084/m9.figshare.28081709 ( https://doi.org/10.6084/m9.figshare.28081709.v1) ¹⁴²⁰

This project contains the following underlying data: •

Density Visualization.jpg

•

Documents by affiliation.jpg

•

Documents by Author.jpg

•

Documents by country or territory.jpg

•

Documents by funding sponsor.jpg

•

Documents by Subject Area.jpg

•

Documents by Year.jpg

•

Factorial Map Of The Documents With The Highest Contributes.png

•

Factorial Map Of The most cited documents.png

•

MostRelevantSources-2024-12-03.png

•

Network Visualization.jpg

•

Overlay Visualization of Scopus, Database Using Vosviewer.jpg

•

tematic evolution berdasarkan title.jpg

•

Thematic map.jpg

•

Topic Dendogram.jpg

•

Tabel 1 Qualitative analysis of the research summary of each abstract

The data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

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Reviewer response for version 2

Reimers

Arne

1 Referee https://orcid.org/0000-0002-6286-554X 1Department of Clinical Chemistry and Pharmacology, Division of Laboratory Medicine, Lund University, Lund, Skåne County, Sweden

Competing interests: No competing interests were disclosed.

22 8 2025

2025

This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

recommendation

approve-with-reservations

This bibliometric study aims at analyzing trends and the current status of published research on Ginkgo biloba. It uses different outcome variables and visualization methods.

There are countless small issues that make this paper difficult to read and understand. For example:

Abstract, results and discussion: this part is supposed to reflect the study's findings. However, the authors state some arbitrarily chosen historical facts about the medical use of Ginkgo biloba.

Abstract, conclusion: instead of a conclusion, the authors state the aims of the study.

The title of this paper says 1420 documents. Also, the list of references consists of 1420 documents. However, in the text it is stated that 1414 documents were retrieved. This should be resolved.

P4: the authors state that they retrieved 1414 relevant documents. Please state how 'relevant' was defined and how many irrelevant documents were excluded.

P4: according to the authors, figure 1 shows that the annual numbers of papers culminated in 61 papers by 2023. From what I can see, the annual number culminated with 130 papers in 2014.

P4: The authors state that the journal Psychopharmacology accepts many manuscripts. It is unclear what is meant by 'many'. Does it have a high acceptance rate? Does it publish a high number of papers per year? (if so, please quantify). Or does it mean that the journal accepts a broad variety of subjects or article types?

P5: 'Ranking three is the Journal of Behavioral Brain Research. This contains information regarding the Journal of Behavioral Brain Research.' This does not make sense, please rephrase.

P5: 'the journal titled Identification of separable cognitive factors in schizophrenia, authored by Keith H. Nuechterlein (…). The journal's abstract states that (…)'. I believe that the word 'journal' should be changed to 'article'.

P6: 'two major receptors that function as primary excitatory neurotransmitters'. Receptors do not function as neurotransmitters. Please rephrase.

Figure 4: This figure is difficult to understand without an explanation. Please explain in the text what dim1 and dim2 are. Further, clusters 1 and 2 appear to be only one single point each, so why are they called clusters? On the other hand, the articles displayed in the figure form a cluster, but this is not mentioned in the text. Moreover, the text mentions a study by Difede et al. (2013). In the figure, there is no study by Difede published in 2013.

P8: 'shows the percentage of documents classified into different subject areas'. Please state how that classification was done.

P9: 'indicates that the examined areas remained unassociated with the other regions delineated by the edges'. That does not make sense. Please rephrase.

P9/10: 'according to Figure 11, in the overlay visualization, it appears that the keywords that are being researched a lot approaching 2016 are the parts colored yellow, namely gluthahione, malonaldehyde, metabolism, prescription, major clinical study, randomized controlled trial (t, addiction, student, students, universities, oxidative stress, chemistry, and nerve degeneration.' To me, it appears that the most researched key words are the green ones in the middle.

P12: 'According to Figure 13, on the thematic map based on the title, the following is an explanation for each keyword in each quadrant in the thematic map resulting from the bibliometric analysis. Here is an explanation of the meaning of each quadrant in the thematic map, and examples of document titles relevant to keywords in each quadrant.' This does not make sense, please rephrase.

Figure 13 looks like a screen shot and should be replaced or at least be cropped to the figure itself.

Results and discussion: the first two sentences are already stated in the introduction and should be deleted. The discussion does not refer to the authors' (= this study's) own findings but represents a medical/historical review of Ginkgo biloba. It needs to be re-written with a clear focus on the bibliometric findings.

Points that must be addressed to make the article scientifically sound:

The abstract and the discussion need to be re-written. The manuscript body needs thorough revision. As a minimum, all issues mentioned above should be resolved.

Note: Almost all figures are impossible to read due to very low resolution. I do not know whether this is the publisher's fault. Fortunately, the authors provide a link to a repository where the figures are available in high resolution.

Is the work clearly and accurately presented and does it cite the current literature?

Partly

If applicable, is the statistical analysis and its interpretation appropriate?

Not applicable

Are all the source data underlying the results available to ensure full reproducibility?

Yes

Is the study design appropriate and is the work technically sound?

Yes

Are the conclusions drawn adequately supported by the results?

Partly

Are sufficient details of methods and analysis provided to allow replication by others?

Partly

Reviewer Expertise:

Clinical neuro- and psychopharmacology

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

SALEH

ARMAN YURISALDI

Neurology, Universitas Pembangunan Nasional Veteran Jakarta, Jakarta, Special Capital Region of Jakarta, Indonesia

Competing interests: No Competing Interests

18 9 2025

Thank you to the reviewers for their kindness in providing feedback and suggestions.

This bibliometric study aims at analyzing trends and the current status of published research on Ginkgo biloba. It uses different outcome variables and visualization methods.

There are countless small issues that make this paper difficult to read and understand. For example:

Abstract, results and discussion: this part is supposed to reflect the study's findings. However, the authors state some arbitrarily chosen historical facts about the medical use of Ginkgo biloba.

Abstract, conclusion: instead of a conclusion, the authors state the aims of the study.

Thank you for your very constructive feedback. We have revised the abstract, results, and discussion sections to focus more on the study's main findings and removed irrelevant historical information. Furthermore, the conclusion section of the abstract has been revised to reflect the study's results and implications, rather than simply the research objectives.

The title of this paper says 1420 documents. Also, the list of references consists of 1420 documents. However, in the text it is stated that 1414 documents were retrieved. This should be resolved.