We chose to use the database of the Web of Science (WOS) core collection provided by Clarivate Analytics for bibliometric analysis because it is widely considered to be the most suitable database for this type of analysis (Ke et al., 2020). To prevent daily updating bias, we conducted the analysis within a single day, taking advantage of the fact that the database remains accessible at all times. Our method for conducting the search in the WOSCC database was as outlined below: TS = (“NF E2 Related Factor 2”OR “Nuclear Factor E2 Related Factor 2”OR “Nuclear Factor Erythroid 2-like 2”OR “NF Erythroid 2-related factor 2”OR “Nuclear Factor (Erythroid-Derived 2)-like 2”OR “Nrf2” OR “nfe2l2”) NOT (“nuclear respiratory factor 2”). The study specifically targeted publications published between 1 January 2000, and 21 October 2022. We excluded any literature not written in English and only included articles for analysis, resulting in 22,040 articles that met our criteria (as illustrated in Figure 1). These publications were downloaded in TXT format on 22 October 2022, for further analysis.

The initial dataset obtained through the designated methodology consisted of key metrics such as the number of papers, citation count, H-index, and relevant data related to affiliations, authors, journals, and geographical information. Following that, we excluded any inaccurately spelled items and eliminated duplicate authors from our analysis. It is worth mentioning that cited references can exist in multiple versions or variations and it is possible for multiple authors to share identical name abbreviations, while cited journals may have distinct formats, all of which may result in inaccuracies in the analysis. So we organized the data manually to prevent any duplication. We successfully managed the issue of inaccurately spelled elements and duplicates by utilizing a thesaurus file. For example, we substitute “Taiwan”/“Hong Kong”/“People R China” with the term “China”. This resource enabled us to consolidate repeated entries, eliminate redundant words, and rectify any spelling errors in a methodical approach. Subsequently, we utilized VOSviewer (version 1.6.18.0), CiteSpace (version 6.1. R6), and the “bibliometrix package 4.1.2”of R software (version 4.2.3) to analyze the refined dataset from a bibliometric perspective.

The publication quantities and their respective citations are obtained through the built-in capability in WOSCC. Among them, the H-index functions as a quantitative measure to evaluate the scholarly achievements or research productivity of individuals (Hirsch, 2005). Originally, the H-index was introduced to assess the scholarly contributions of individual researchers. Over time, its scope has broadened to include assessing research groups, institutions, and research communities on a national or regional scale, as well as its application in evaluating academic journals. On the other hand, the G-index measures the maximum number of publications that have achieved a citation count equal to or higher than the H-index (Abbas, 2012). Furthermore, we use the impact factor (IF) and the latest edition of Journal Citation Reports (JCR) as important indicators to evaluate the scientific value of research (Eyre-Walker and Stoletzki, 2013).

Various software tools were employed for conducting bibliometric analysis in the study. To visualize and construct bibliometric networks, we relied on the VOSviewer software, developed by Leiden University in the Netherlands. This software facilitated in-depth analysis of bibliographic coupling, co-citation, co-occurrence and international collaborations (van Eck and Waltman, 2017). Due to its capacity to map and detect clusters in a network simultaneously, the software was used in combination with clustering methods to divide networks into separate clusters, taking into account the intensity of connections between nodes. Additionally, we applied the R4.1.2-based “bibliometrix” to generate visualizations describing the relationships between different journals and conduct three-field plot analysis. A “three field plot” is a graphical representation that visually depicts the relationships among three distinct entities, it provides insights into the global nature of research collaborations and the distribution of research activities in a given field. Overall, we use “three field plot” as an effective tool for visually summarizing complex relationships and interactions among countries, institutions, and authors in research related to Nrf2. Furthermore, CiteSpace, a software tool created by Professor (Chen et al., 2009), was employed in the analysis to produce dual-map overlays for journals, perform cited keywords analysis, and identify references exhibiting notable citation bursts. The dual-map function helped depict the subject distribution of academic journals by placing citing journals on one side and cited journals on the other, illustrating their relationship. The size of nodes in the network was determined by the parameters weight, which includes the number of publications, number of citations, or frequency of occurrence. Larger nodes were attributed to higher weight. Each node and line in the network were assigned a color representing its respective cluster. The lines between nodes represented the connections among them. Moreover, the Total Link Strength (TLS) was utilized to evaluate the total co-authorship and co-citation links among different countries, institutions, and authors.

VOSviewer and CiteSpace are both tools used for bibliometric analysis. They share the common purpose of visually revealing literature networks, collaborative relationships, and thematic trends. VOSviewer emphasizes co-occurrence analysis and customizable network visualization to understand keyword associations and collaborations. CiteSpace focuses on temporal analysis and citation networks to uncover research history and impact. Employing both tools in this study may offer a more thorough comprehension. In addition to that, online tools facilitate the generation of chord diagrams of countries. These diagrams involve dividing the circle based on proportional country distribution and linking interrelated nations through chord segments to portray their connections. The width of these segments can convey the intensity of these associations.

According to our search strategy, overall 22,040 literature pieces were gathered spanning from 2000 to 2022. The yearly publication outcomes related to Nrf2 are presented in Figure 2, excluding incomplete data for articles published in 2022. The interest in Nrf2 has been increasing significantly across the most recent 20 years. In 2000, there were only 22 publications related to Nrf2, which increased to 1,248 in 2015, and reached a record high of 3,181 in 2021. Since 2018, there has been a significant expansion in the amount of published articles. The overall global publications in 2021 on this topic are almost 144.59 times greater than those in 2000, which is a remarkable achievement. The fast-paced growth of publication number indicates a rising interest among scholars in this field, which means scholars conducting research and the flourishing of theories related to Nrf2 are evident.

Research on Nrf2 has gained global attention, with ongoing studies conducted in 117 countries and regions worldwide. The publication count was used to determine the ranking of the top 10 countries/regions, and it also includes information on their citation frequency, H-index and centrality. The centrality of each country/region indicates its importance in the network (as seen in Table 1). Centrality measures the intensity of links among nodes within a network, serving as an indicator of the importance and impact. The top 10 countries/regions that have published over 500 papers on Nrf2 are mainly from Asia, Europe and North America. China leads the pack with 9,594 counts (43.53%) in terms of publication numbers, followed by the United States with 4,931 counts (19.92%) and South Korea with 1,844 counts (8.37%). The combined publications from China and the United States make up 66.03% of the total, which is significantly higher than any other country.

The United States is at the forefront in terms of citation frequency, with a remarkable total of 261,776 citations, followed by China (179,971) and Japan (88,410). Significantly, the United States had a citation count of 53 per publication, highlighting its strong impact. In contrast, China had a high citation count but a relatively low citation/publication ratio compared to the top 10 countries, standing at 19. Notably, England demonstrated a high citation/publication ratio of 52, indicating the high quality of its published papers despite a relatively lower publication count. With regards to the H-index, the United States held the top position with a score of 208, while Japan and China achieved H-indices of 142 and 118, respectively.

Figures 3A, B provide insights into the collaborative efforts among the top 39 countries based on their publication output. The analysis highlights that these countries can be classified into five distinct clusters in VOSviewer, reflecting varying degrees of collaboration. These clusters are visually represented using different colors. Figure 3C illustrates the collaborative relationships among the countries mentioned earlier in the form of a world map. The top 30 countries are represented using a chord diagram, where each country is assigned a distinct color. The entire circle is divided proportionally based on each country’s representation, the wider the chord segments, the stronger the collaborative relationships among these countries are (shown in Figure 3D). In conclusion, the majority of collaboration was centered around China and the United States, followed by Japan, South Korea, Germany and the United Kingdom, were the primary focus of collaboration, whereas there was a limited level of collaboration with other countries. And the metrics used in this study are listed in Table 2.

The analysis of research institutions can be used to determine the global distribution of Nrf2 research and to identify potential collaboration partners. In Table 3, you can find the top 10 institutions, with China Medical University being the most productive (459, 2.08%), followed by the Chinese Academy of Science (343, 1.56%) and Tohoku University (324, 1.47%). China dominated the top 10 institutions, with the majority (8 out of 10) being from this country, representing 11.26% of the total papers. Johns Hopkins University stands out with the highest average citations (107.7933) and H-Index (108), followed closely by Tohoku University with an average citation of 82.5957 and an H-Index of 97. However, the other institutions have average citations below 30 and H-Index below 60.

Figure 4 generated using CiteSpace, depicts an institutional co-occurrence map illustrating the leading 10 institutions in Nrf2 research. The map emphasizes their publication contributions and prominence within the field. The visualization represents institutions as nodes, with their sizes reflecting their significance in the field. The connections between nodes indicate collaboration, and the links are color-coded to represent the specified time period. If a node has a centrality exceeding 0.1, it indicates that the node is a central node, which is relatively important and has a significant influence in the study. These nodes are marked with purple circles.

There has been a total of 1,927 academic journals that have published articles related to Nrf2. The leading 20 journals in terms of publishing articles on Nrf2 are presented in Table 4, making up 27.00% of all the articles. The annual and cumulative publications of the journal are displayed in the Figures 5A, B. The publication volume of Antioxidants has experienced a significant increase in the past 2 years, showing a steep upward trend. Free Radical Biology and Medicine holds the top spot for the highest number of published studies on Nrf2, (8.101, Q1) (613). This is followed by Oxidative Medicine and Cellular Longevity (7.310, Q2) (576), and Antioxidants (7.675, Q1) (441). Among the top 20 journals based on publication count, half of them is classified as Q1 in the Journal Citation Reports (JCR), while 70% of these journals have an Impact Factor (IF) exceeding 5. Remarkably, The Journal of Biological Chemistry demonstrated the highest H-index (92) and G-index (165), closely followed by Free Radical Biology and Medicine with an H-index of 89 and a G-index of 132. Plos One ranked third with an H-index of 69 and a G-index of 99, suggesting the inadequate quality of a considerable number of studies.

Figure 5C displays the Top 100 co-citation journal network, consisting of 5 clusters, which was created using VOSviewer. The red cluster, which is the largest among the clusters, consists of 40 journals that primarily specialize in Biochemistry, Pharmacology, Toxicology, and Food Science, with a particular emphasis on Immunology and Molecular Sciences. Notably, Free Radical Biology and Medicine holds a prominent position within this cluster. This journal has published a considerable amount of basic and clinical research, focusing primarily on the mechanisms underlying altered metabolism and redox signaling.

The journals represented by the green cluster cover research areas such as cancer, autophagy, cell metabolism, gene and development, and nucleic acids. Among them, the Journal of Biochemistry occupies the central position in the co-citation network with the highest quotation number and strong co-citation intensity. This journal primarily focuses on molecular and cellular processes and fundamental mechanisms.

Antioxidants and Redox Signaling and Journal of Clinical Investigation hold a prominent position within the blue cluster. This cluster primarily encompasses the fields of medicine and biomedical sciences, including pathology, physiology, immunology, pharmacology, respiratory medicine, cardiovascular medicine, nephrology, diabetes, as well as antioxidants and redox signaling. The yellow cluster focuses on pharmacology, toxicology, biochemistry, and biophysics. Key journals within this cluster include Biochemical and Biophysical Research Communications and Biochemical Journal. The purple cluster represents the field of neuroscience, with the Journal of Neurochemistry leading the cluster. These journals have made significant contributions to promoting Nrf2 research.

According to the analysis shown in Figure 5D, in terms of centrality, Journal of Biological Chemistry ranked first with a centrality value of 0.83, followed by Proceedings of The National Academy of Sciences of The United States of America with 0.72 and Free Radical Biology and Medicine with 0.28. These journals exhibited high centrality, indicating their significant impact in the field.

The dual-map visualization of journals provides valuable insights into topic distribution, the evolution of citation trends, and shifts in research emphasis among different scholarly publications. The labels on the left side of the dual map indicate the journals that are citing, while the labels on the right side indicate the journals being cited. The citation context is visually represented by a colored curve connecting the citing map to the cited map (Chen and Leydesdorff, 2013). Based on the dual-map overlay (Figure 6), two primary citation paths were observed. The publications primarily belonged to the fields of life sciences and healthcare, encompassing molecular, biological, and immunological areas, as well as medicine, medical, and clinical domains. Journals across various fields, including molecular biology, genetics, environmental science, toxicology, nutrition, health, nursing, medicine, chemistry, materials science, and physics, featured the most frequently cited articles.

The VOSviewer analysis also included the cooperation network of authors, revealing that 96,136 authors were involved in Nrf2-related studies.

Table 5 presents the top ten core authors and their corresponding data in terms of publications and citations. A minimum of 37 articles published by an author was set as a criteria, and 78 authors met the criteria. Figure 7A illustrates the division of the co-authorship network into five distinct clusters, each identified by a unique color. Within the figure, individual circles symbolized authors, while the lines connecting the circles indicated the interconnections among them. Different colors showed the cooperation cluster between authors. Masayuki Yamamoto held the top position in terms of publications with 307 articles, followed by Liu Yang with 166 articles, Feng Lin with 113 articles, and Wu Pei with 107 articles. It is evident that the author centrality was relatively low, with only two authors having centrality values of 0.05 or higher.

When setting a minimum threshold of 675 citations per author, a total of 55 individuals were identified as co-cited authors, indicating that they were cited simultaneously in publications (Figure 7B). Itoh K. emerged as the top-ranked author with the highest number of citations, totaling 3669. Nguyen T. claimed the second position with 2148 citations, while Kensler T. W. secured the third position with 1981 citations. Notably, among these authors, Itoh K. displayed a remarkable centrality value of 0.90, followed by Kobayashi A. with 0.46, Hayes J. D. with 0.39, and Dinkova-Kostova A. T. with 0.11, indicating their significant influence and connectivity within the research network.

Figure 7C depicts the interconnected relationships among countries, authors and institutions within the field of Nrf2 research. In summary, a significant proportion of authors, 90% to be precise, have affiliations with institutions in China. Moreover, out of the 10 institutions represented, 6 of them are Chinese, indicating a strong presence and contribution from China in the field.

A co-citation network arises from examining the citation relationships among literature, while conceptual clusters gather related papers that share common citation patterns within this network. Co-citation networks investigate how literature references are cited by multiple papers, and conceptual clusters unite papers with similar citation patterns. Based on Figures 8A, B, the most cited article by K Itoh, titled “An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements” revealed the critical role of the Nrf2/small Maf heterodimer in activating phase II detoxifying enzyme genes. This heterodimer combines with antioxidant response elements (AREs) in DNA and regulates the genes associated with detoxification and antioxidant defense mechanisms.

In Figure 8C, the network visualization map depicts the connections among cited references, where nodes symbolize the references and links represent co-citation associations. The size of the nodes correlates with the number of co-citations, while the color gradient (ranging from purple to yellow) signifies distinct years spanning from 2000 to 2022. CiteSpace categorized the relevant clusters into 20 groups (shown in Figure 8D), encompassing various topics such as Nrf2 mutation, cigarette smoking, p62-dependent autophagic degradation, bardoxolone methyl, young grass carp, antioxidant induction, catalytic subunit gene, Nrf2-dependent mechanisms, alpha receptor, major metabolite receptor, cellular apoptosis, rat brain, Keap1 loss, inhibiting ferroptosis, non-alcoholic fatty liver disease gene, redox control, protein-protein interaction, melanoma cell, nf-e2 related factor, and oxygenase-1 expression.

A sudden and remarkable increase in the number of citations received by specific articles within a defined time period is referred to as a citation burst. It serves as a valuable tool for identifying emerging research topics and gaining insights into current trends within relevant academic domains (Miao et al., 2022). We identified the top 45 references that experienced a highest citation burst (Figure 9). The blue line depicts the time span, while the red line represents the surge duration, illustrating the duration of the citation surge within a specific time period. The first two citation burst began in 2000, entitled “Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain” (Itoh et al., 1999) and “Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages” (Ishii et al., 2000). The article “Role of nrf2 in oxidative stress and toxicity” (Ma, 2013) by Qiang Ma, published in the Annual Review of Pharmacology and Toxicology in 2013, had the highest citation burst with a strength value of 177.76. The burst occurred from 2014 to 2018. Another significant citation burst was observed for the article “Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway” (Kensler et al., 2007) by Thomas W Kensler, also published in the same journal, with a strength value of 165.52. According to the findings, 2014 exhibited the highest frequency of new citation bursts, totaling 6 occurrences. This was subsequently followed by the years 2017, 2019, and 2020, each with 4 new citation bursts. These observations suggest that the papers with significant bursts in 2014, as well as in the recent 5 years, have contributed to a surge in related research activities. There are ten citation bursts until 2022, these articles collectively investigate the role of the Nrf2-Keap1 signaling, Nrf2/HO-1 system in development, cellular defense against oxidative stress, as well as its crucial involvement in inflammation, redox balance, tumors, chronic diseases, and cell death processes such as lipid peroxidation and ferroptosis. This indicates that research focused on Nrf2 is still actively being pursued.

Keywords offer a comprehensive analysis of the cutting-edge of Nrf2 research, serving as a summary of the article’s essential content. VOSviewer and CiteSpace were utilized to create visual charts. To streamline the keyword selection process, we eliminated irrelevant terms and combined synonymous terms. This ensured a more focused and comprehensive representation of the keywords. In total, 43,177 keywords were extracted from 22,040 documents. By analyzing the data, we identified a collection of 315 keywords based on their occurrence frequency, selecting those that appeared more than 62 times. The co-occurrence of keywords is visualized in a network diagram using VOSviewer. The connections between keywords indicate their relationships in terms of co-occurrence. The keywords are grouped into five clusters according to their research direction (Figure 10A). The red cluster, which is the most extensive, comprises 80 keywords related to oxidative stress, antioxidant defense mechanisms, apoptosis, mitochondrial dysfunction, regulation of metabolism and homeostasis, hepatotoxicity and nephrotoxicity, aging and longevity, DNA damage and repair, lipid peroxidation, and the effects of different substances (including drugs, environmental toxins, and natural compounds) on biological systems. The green cluster is dedicated to exploring cancer-related subjects, encompassing breast, colorectal, lung, and prostate cancers. It delves into autophagy, cell proliferation, tumor metastasis, angiogenesis, and protein degradation. Prominent components within this cluster include Keap-1, Nqo1, p53, and p62. Additionally, it discusses chemotherapy medications like cisplatin and natural compounds such as sulforaphane. The blue cluster focuses on metabolic disorders, cardiovascular and kidney diseases, lipid metabolism, insulin resistance, mitochondrial biogenesis, regulation of adipose tissue and skeletal muscle, diet and nutrition, as well as the molecular mechanisms and pathological processes associated with Ampk, SIRT1, and PPAR-gamma pathways. The yellow cluster pertains to inflammation and immune response, primarily in respiratory diseases. Key factors involved encompass heme oxygenase-1, NF-kappaB, NLRP3, p38 MAPK, PI3K/Akt, TNF-alpha, and Bach1. The purple cluster centers around neurological disorders such as ischemia-reperfusion injury, Alzheimer’s disease, and Parkinson’s disease. It also encompasses neurotrophic factors, iron ions, and iron-induced cell death. Notable factors within this cluster include BDNF, DJ-1, PI3K, and others. The overlay map of keywords, organized by publication year, demonstrates the dynamic shifts in research focus over time (Figure 10B). More recent keywords, such as ferroptosis (2021.01), pyroptosis (2020.97), and gut microbiota (2020.80), are highlighted on the map, while keywords like NLRP3 (2019.95), polysaccharides (2019.86), mitophagy (2019.84), NAFLD (2019.83), and osteoarthritis (2019.69) are relatively less recent. The color spectrum in Figure 10C, ranging from purple to yellow, reflects the varying popularity of top 30 keywords over a span of 20 years. Yellow hues indicate a higher frequency and greater significance, while purple shades suggest a diminishing level of importance.

In addition to the Citespace analysis, we identified and presented the most prominent 27 clusters of keywords associated with Nrf2 in Figure 10D. These clusters encompass diverse research domains and shed light on the main focuses within the academic community. During the period from 2000 to 2010, Nrf2 literature primarily concentrated on oxidative stress, antioxidant defense, tumor biology, inflammation and immune regulation, as well as neuroprotection and neurodegenerative diseases. Subsequently, Nrf2 research advanced its comprehension of signal pathways, regulatory mechanisms, and therapeutic drugs in these areas from 2011 to 2022. It progressively broadened its scope to encompass additional fields, such as chronic diseases (e.g., cardiovascular diseases and diabetes) and metabolic regulation (including energy, lipid, and glucose metabolism). Furthermore, there was an exploration of environmental toxicity and exposure to chemical substances in the research.

To our knowledge, this study pioneers a thorough and systematic bibliometric analysis exploring the basis and research frontiers of Nrf2, covering a wide range of aspects. In this research, VOSviewer, CiteSpace, and R software tools were employed to examine the research patterns and primary areas of emphasis concerning Nrf2 over the last two decades in the Web of Science Core Collection. In this study, we conducted an analysis of a comprehensive dataset consisting of 22,040 articles originating from 11,419 institutions across 117 countries. The involvement of 96,136 authors was recorded, and the articles were published in a total of 1,927 journals.

During the period from 2000 to 2021, there was a remarkable increase in the annual publication output and citation frequency of Nrf2 research. This upward trend became more pronounced after 2018, indicating a growing interest and significant impact of Nrf2 in the scientific community. Asia, Europe, and North America lead in Nrf2 research publications, with China making notable contributions to the field, with the United States and South Korea coming after. Remarkably, China accounted for the majority of the top 10 prolific institutions in Nrf2 research, including renowned institutions like China Medical University, Chinese Academy of Science, and Nanjing Medical University. And Johns Hopkins University stands out with the highest average citations and H-Index, followed closely by Tohoku University higher value. Except that, the United States had higher H-index and average citation values compared to China, indicating the exceptional research output. While China has made remarkable progress and holds a prominent position in Nrf2 research, there is still potential for enhancing collaboration across regions and strengthening academic impact. The current distribution of research in this field at the international level reveals an imbalance, with most collaboration centered around China and the United States. Japan, South Korea, Germany, and the United Kingdom have also been primary collaborators, while cooperation with other countries remains relatively limited.

Research progress in the field of Nrf2 has been documented in a range of journals across diverse disciplines, underscoring the widespread interest in understanding Nrf2’s role in disease development and treatment. Studies focusing on Nrf2 are predominantly published in journals that span multiple fields, including biomedical and life sciences, molecular science and cell biology, pharmacology and drug research, food science and nutrition, as well as multidisciplinary research in general science, including Plos One and Scientific Reports. There are a large number of high-quality papers in Nrf2 research. Based on the Journal Citation report (JCR), the number of Q1 journals accounts for half of the top 20 journals. And most of the publishers are in the United States, Central and Western Europe. Among the top 20 journals with the highest publication count, Redox Biology exhibited the highest impact factor (IF) of 10.787, establishing itself as a prominent journal since its inception in 2013. Free Radical Biology and Medicine, with an impact factor of 8.101, emerged as the most prolific journal in its field, alongside Oxidative Medicine and Cellular Longevity and Antioxidants. Free radical biology and medicine, initiated by the Society of Redox Biology and Medicine (SFRBM), covers a wide range of fields, including signal transduction, oxidative stress, aging, metabolic regulation, mitochondrial function and antioxidant enzymes. It is worth mentioning that the publication of Antioxidant has surpassed that of other journals since 2018, indicating the magazine’s great potential in the field of Nrf2 research. As one of the top 20 journals cited most frequently, the Journal of Biochemistry stands out because of its high H index and G index. It covers many research fields, such as biochemistry, molecular biology, cell biology, bioinformatics and enzymology.

Masayuki Yamamoto is an eminent author in the field of Nrf2 research. He stands out for his significant contributions and holds the highest publication output in Nrf2 studies. His team was the first to describe the structure and regulatory mechanism of Nrf2, unveiling its pivotal role in antioxidant defense and cellular stress response. One of his influential articles is a comprehensive review that explores the mechanisms and functionalities of the KEAP1-NRF2 system. It emphasizes the essential involvement of NRF2 in maintaining cellular redox balance and investigates its regulatory mechanisms in antioxidant defense, detoxification metabolism, and cellular stress response, offering insights into both normal and pathological conditions (Yamamoto et al., 2018). Itoh K. rose to prominence as the leading author with the most citations and centrality value, followed by Nguyen T. and Kensler T. W. The groundbreaking research publication of Itoh K. titled “Keap1 inhibits the nuclear activation of antioxidant response elements by Nrf2 through interaction with the amino-terminal Neh2 domain" (Itoh et al., 1999) which appeared in Genes and Development in 1999, garnered significant attention and had a profound impact within the academic community at that time. In this paper, Keap1 is considered to act as a critical sensor alongside Nrf2 in the context of oxidative stress, playing a pivotal role in the signaling pathway, that activates transcription via Nrf2’s nuclear shuttling mechanism, which lays the foundation for further in-depth investigations into the function of Nrf2. Kensler T. W’s article titled “Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway" (Kensler et al., 2007) in the Annual Review of Pharmacology and Toxicology is one of the top 45 references with the strongest citation bursts. The article highlights the critical role of the Keap1-Nrf2-ARE signaling pathway in allowing cells to adapt and safeguard against acute and chronic cellular damage caused by environmental stresses.

This study provides a thorough of diverse research findings and areas of interest observed over the last two decades. Additionally, it presents an overview of the advancements and trends within Nrf2 during this period. As diverse perspectives show in publication, keyword clustering, and highly-cited articles, we have successfully identified the principal research areas and focal points associated with Nrf2. These mainly encompass research into oxidative stress, cancer, glycolipid metabolic disorder, inflammation, and neurological disorder. The findings of these studies indicate that targeting Nrf2 activators as a therapeutic approach holds considerable potential.