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Resveratrol’s bibliometric and
visual analysis from 2014 to 2023
Haoyue Wei
1
, Guowei Fang
2
, Weina Song
3
, Hongye Cao
1
,
Ruizhe Dong
1
and Yanqin Huang
2
*
1
The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China,
2
Department of Endocrinology, Affiliated Hospital of Shandong University of Traditional Chinese
Medicine, Jinan, China,
3
Department of Pediatric Respiratory and Critical Care, Qilu Hospital of
Shandong University Dezhou Hospital, Dezhou, China
Introduction: Resveratrol (RSV) is a natural polyphenolic compound derived from a
variety of plants that possesses a wide range of biological activities, including
antioxidant, anti-inflammatory, antitumor, antibacterial, antiviral, anti-aging, anti-
radiation damage, anti-apoptosis, immune modulation, regulation of glucolipid
metabolism, inhibition of lipid deposition, and anti-neuro. It is therefore
considered a promising drug with the potential to treat a wide range of diseases.
Method: In this study, using Web of Science Core Collection (WoSCC) and CiteSpace
bibliometric tool, VOSviewer quantitatively visualized the number of countries, number of
authors, number of institutions, number of publications, keywords, and references of
16,934 resveratrol-related papers from 2014–2023 for quantitative and qualitative analysis.
Results: The results showed that an average of 1693.4 papers were published per
year, with a general upward trend. China had the most publications with 5877.
China Medical University was the institution with the largest number of
publications and the highest number of citations in the field. The research
team was mainly led by Prof. Richard Tristan, and the journal with the highest
number of published papers was Molecular. Dietary polyphenols, oxidative stress,
and antioxidant and anti-inflammatory effects are the most frequently cited
articles. Oxidative stress, apoptosis, expression, and other keywords play an
important role in connecting other branches of the field.
Discussion: Our analysis indicates that the integration of nanoparticles with RSV is
poised to become a significant trend. RSV markedly inhibits harmful bacteria, fosters
the proliferation of beneficial bacteria, and enhances the diversity of the intestinal
flora, thereby preventing intestinal flora dysbiosis. Additionally, RSV exhibits both
antibacterial and antiviral properties. It also promotes osteogenesis and serves a
neuroprotective function in models of Alzheimer's disease. The potential
applications of RSV in medicine and healthcare are vast. A future research
challenge lies in modifying its structure to develop RSV derivatives with superior
biological activity and bioavailability. In the coming years, innovative pharmaceutical
formulations of RSV, including oral, injectable, and topical preparations, may be
developed to enhance its bioavailability and therapeutic efficacy.
KEYWORDS
resveratrol, bibliometrics, Web of Science, VOSviewer, CiteSpace, pharmacological action
Frontiers in Plant Science frontiersin.org01
OPEN ACCESS
EDITED BY
Debasis Mitra,
Graphic Era University, India
REVIEWED BY
Jovana Rajkovic,
University of Belgrade, Serbia
Viralkumar B. Mandaliya,
Marwadi University, India
*CORRESPONDENCE
Yanqin Huang
dahuang79@126.com
RECEIVED 25 April 2024
ACCEPTED 23 September 2024
PUBLISHED 08 October 2024
CITATION
Wei H, Fang G, Song W, Cao H, Dong R and
Huang Y (2024) Resveratrol’s bibliometric and
visual analysis from 2014 to 2023.
Front. Plant Sci. 15:1423323.
doi: 10.3389/fpls.2024.1423323
COPYRIGHT
©2024Wei,Fang,Song,Cao,Dongand
Huang. This is an open-access article
distributed under the terms of the Creative
Commons Attribution License (CC BY). The
use, distribution or reproduction in other
forums is permitted, provided the original
author(s) and the copyright owner(s) are
credited and that the original publication in
this journal is cited, in accordance with
accepted academic practice. No use,
distribution or reproduction is permitted
which does not comply with these terms.
TYPE Systematic Review
PUBLISHED 08 October 2024
DOI 10.3389/fpls.2024.1423323
1 Introduction
RSV is a natural polyphenol, an antitoxin produced by many
plants when they are stimulated, also known as 3,5,4’-
trihydroxystilbene, with a molecular formula of C14H12O3, a
relative molecular weight of 228.25, and both cis and trans
configurations. It belongs to the non-flavonoids class of
polyphenolic compounds (Salehi et al., 2018). Mainly found in
grapes, tiger nuts, peanuts, blueberries, mulberries, cassia seeds, and
Polygonum multiflorum (Tian and Liu, 2020). Modern
pharmacological studies have shown that RSV has a variety of
pharmacological effects, including anti-inflammatory (Berman
et al., 2017), antioxidant (Meng et al., 2020), and other
pharmacological activities. With the deepening research on the
pharmacological effects of RSV, it has been found that RSV exerts its
pharmacological effects in the treatment of diabetes (Barber et al.,
2022), obesity (Barber et al., 2022), antibacterial, anti-
atherosclerosis (Chen et al., 2016), and neuroprotection
(Azargoonjahromi and Abutalebian, 2024) through multiple
pathways and multiple targets.
In addition to being published in the review section, many
bibliometric articles are also published in the systematic review
section (Gu et al., 2021;Zhu et al., 2022;Liu et al., 2024;Zhi et al.,
2024). Bibliometrics is similar to systematic reviews in terms of
searching the literature and can be used to study different and
important areas of investigation and to obtain a general overview of
the published literature (Lubowitz et al., 2023). Bibliometrics
reviews all fully published articles in biomedical journals,
including diverse research methodologies such as descriptive
studies, observational studies, experimental studies, qualitative
studies, and systematic reviews, thus illuminating the robustness
of the available evidence (Manoj Kumar et al., 2023). The analysis of
bibliometrics data is facilitated by specialized software such as
VOSviewer and CiteSpace (Manoj Kumar et al., 2023). Given that
bibliometrics often engages with extensive data sets from databases,
it encompasses processes like data retrieval, preprocessing, network
extraction, normalization, mapping, analysis, and visualization,
with findings presented through tables, citation maps, web
displays, and graphical representations. Bibliometrics furnishes a
holistic perspective and analytical insights into research fields,
essential for discerning research trends and impacts, particularly
when systematic reviews necessitate substantial literature data for
contextual evaluation. The interrelation between bibliometrics and
systematic reviews lies in their shared objective of summarizing and
analyzing existing research, albeit with distinct emphases.
Bibliometrics prioritizes quantitative metrics such as reference
counts, citation patterns, and research trajectories, while
systematic reviews concentrate more on the quality of research
and the appraisal of results. Though bibliometrics may not directly
belong to the realm of bioinformatics, the insights and analyses it
offers can furnish valuable contextual information, trend
perspectives, and resource evaluations pertinent to bioinformatics
research (Montazeri et al., 2023). While bibliometrics does not
directly assess research quality, systematic reviews may utilize this
data to pinpoint and evaluate high-impact, widely cited studies.
Furthermore, bibliometrics can underscore recent advancements
and pressing issues within a discipline, thereby guiding systematic
reviews to concentrate on contemporary hot topics and
principal challenges.
In the past few years, there have been a lot of research papers on
RSV. These papers summarize the role and mechanism of RSV, look
at the current state of research, make suggestions for future
research, and give a scientific basis for its development and use.
Previous bibliometric analyses have elucidated the pivotal role and
mechanisms of RSV in anticancer research. The emerging frontiers
in this field are anticipated to concentrate on topics such as
resveratrol-induced apoptosis, tumor microenvironment, and
synergistic effects (Fu et al., 2024). Another bibliometric study
explored RSV’s impact on cognitive function, assessing its
influence on various cognitive disorders and underlying
mechanisms. Areas of focus include the regulatory effects of RSV
on neuronal damage in healthy adults, older adults,
postmenopausal women, Alzheimer’s disease patients, individuals
with diabetes-related cognitive impairments, psychiatric disorders,
post-stroke cognitive deficits, and neonatal ischemic injury (Tu
et al., 2023). A study on RSV and neuroinflammation suggests that
oxidative stress and inflammatory responses are critical in
neurodegenerative diseases, and RSV may mitigate these
processes through its antioxidant and anti-inflammatory
properties (dos Santos et al., 2024). RSV exerts significant anti-
inflammatory effects, mitigating HIF-1a-mediated angiogenesis
and impeding the progression of Asperger Syndrome through the
TLR4/NF-kB signaling pathway (Guo et al., 2023). In 2022, Robin
Haunschild and Werner Marx reviewed 3,344 publications on the
health benefits of RSV in wine and grapes. Their findings indicate
that moderate red wine consumption may offer health advantages,
whereas excessive consumption could lead to cirrhosis and cancer.
The study categorized the authors’keywords into six domains:
beverage-related, compound-related, disease-related, effect-related,
mechanism-related, and broader keywords, and analyzed their
usage (Haunschild and Marx, 2022).
Previously, Andy Wai Kan Yeung and colleagues conducted
bibliometric research on countries contributing significantly to RSV
research, highlighting major publications and their focal areas. Over
half of the pertinent literature has emerged since 2013, partly due to
heightened scientific activity in China. This review provides a
succinct overview of research on RSV and its derivatives (Yeung
et al., 2019). Our research conducts a bibliometric and visual
analysis of RSV-related literature spanning from 2014 to 2023. It
provides a thorough examination of various aspects, including
research countries, institutions involved, author collaborations,
journal publications, highly cited works, and keywords. Building
upon previous bibliometric studies, this paper explores the
comprehensive effects and mechanisms of RSV concerning cancer
prevention, cognitive function, and neuroinflammation. Currently,
our understanding of the specific mechanisms underlying RSV’s
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effects remains insufficient, necessitating further foundational
research. Future investigations should emphasize the efficacy and
safety of RSV in practical clinical settings.
2 Materials and methods
2.1 Data sources
We selected the WoSCC as the primary database for this study
because of its extensive coverage of over 12,000 scholarly journals
and frequent use by researchers. We used “Resveratrol”as the
search term, set the search period as January 2014–December 2023,
set the language as “English,”and limited the types of articles to
“article”and “review article.”The search deadline was March 18,
2024.Weexcludedconferenceproceedings,letters,online
publications, retractions, and other irrelevant documents,
resulting in a total of 17,434 RSV-related documents. Two
researchers independently searched and screened the above data,
with the third senior researcher making the final decision in cases of
disagreement. We imported the data into CiteSpace to remove
duplicates, and we finally obtained 16934 articles, including 2772
reviews and 14162 articles. We conducted all literature searches and
downloads on the same day to reduce the number of citations
resulting from frequent database updates.
2.2 Bibliometric analysis software
We exported the screened documents in plain text and tab-
delimited file formats, containing full records and cited references,
respectively, and then imported them into VOSviewer 1.6.18,
CiteSpace 6.1.6, Pajek 5.16, Scimago Graphica 1.0.35, and the
“Bibliometrix”R software package (R Studio, version 4.2.0).
“Bibliometrix”R package (R Studio, version 4.2.0). The main
indicators analyzed were the number of publications, country/
institution/author partnerships, keyword emergence and co-
occurrence clustering, and trends in research themes (Figure 1).
3 Results and analysis
3.1 RSV literature volume and
trend analysis
In this pie chart, we illustrate the distribution of publications
across various countries in the domain of RSV research (Figure 2A).
The chart reveals that China holds a predominant and unequivocal
lead in the volume of published works, whereas other nations such
as the United States, Italy, and Iran contribute a relatively modest
share. This data underscores that China’s research efforts in RSV are
significantly more concentrated compared to those of other
countries. The color-coded markers in the chart facilitate a clear
identification of the publication percentages by country. The
volume of publications within a specified timeframe reflects the
trajectory of research endeavors. From 2014 to 2023, we compiled a
total of 16,934 papers (comprising 2,772 review articles and 14,162
research articles) about RSV, averaging 1,693.4 publications
annually. Over the past decade, there has been a discernible and
steady rise in academic output in this field. Since 2017, annual
publications have consistently surpassed 1,500, culminating in a
peak of 2,112 publications in 2023. This represents a 77.48%
increase compared to 2014, underscoring the substantial research
value of this area and a notable expansion in research activity.
Furthermore, there has been a marked upsurge in the exploration of
RSVs. To illustrate the annual publication trend, we employed the
exponential equation (y = 103.1x + 1126.3) (R² = 0.9757), where (x)
denotes the year and (y) signifies the annual publication volume.
The fitted curve accurately represents this equation (Figure 2B),
predicting a sustained upward trend in annual publications,
reflecting an escalating interest in RSVs. Thus, it is plausible to
anticipate a period of significant advancement in this domain in the
forthcoming years. The investigation into RSV has garnered
substantial scholarly interest, as evidenced by the rising number
of academic publications. This emerging field is attracting more
researchers and emphasizing its importance in the academic
community. We anticipate the field’s continued expansion and
the innovative role of novel nanomedicines in enhancing the
therapeutic efficacy of RSV. This growth is expected to attract
additional funding, talent, and stakeholder engagement, fostering
heightened investment and collaboration between academia and
industry in RSV-related innovations and technologies.
3.2 Distribution of RSV research countries
A total of 136 countries and regions have published RSV articles
by scholars, and we use the “Bibliometrix”R package to visualize the
network of national collaborations. The cooperation between these
regions forms four different clusters. The thickness of the lines
connecting the spheres indicates the degree of cooperation between
countries. Each sphere represents a country. The size of the sphere
represents the total number of articles published by the country in
the time period, and the color of the sphere represents the intensity
of cooperation between the country and other countries. According
to the global productivity map (Figure 3A), most of the papers are
published in Asian, North American, and European countries.
China published the largest number of papers, with 5,877, or
34.7% of the total, followed by the United States with 14.2% (n =
2404) and Italy with 7.04% (n = 1192) (Table 1). This is closely
related to the level of economic development in these countries and
the importance attached to scientific research by their respective
governments. The number of publications often reflects a country’s
or region’s status in the field. China and the United States have the
most publications in RSV, indicating their academic status and
influence. Close cooperation between the two countries will
promote theoretical innovation and address existing technical
challenges in the field.
This graph illustrates the strength of international collaboration
in RSV research (Figure 3B). Each node represents a country, with
its size proportional to the total number of publications in RSV
research from that nation. The color gradient in the figure denotes
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the intensity of cooperation, with lighter hues indicating a lower
frequency of collaboration and darker hues signifying a higher
frequency. For instance, the thicker connections between China and
the United States, South Korea, Poland, and Turkey highlight a
robust network of frequent cooperation. This visualization reveals
that the United States, China, and several European and Asian
countries are central to global RSV research collaborations,
depicting a comprehensive international cooperation landscape.
Citation bursts are critical for identifying projects with a
significant increase in the number of citations within a given
timeframe. They provide insights into the dynamics and
trajectory of a research field. Analyzing projects with rapid
citation growth can help researchers identify emerging trends in a
given research area that have caught their attention. We display the
citation explosion for the top 5 countries (Figure 3C). From 2014 to
2016, Belgium and Scotland showed a significant increase in the
number of publications, as indicated by the dark red line in the
figure. This line reflects the intensity of the citation explosion in the
most influential countries. Notably, Bangladesh, a developing
nation in Asia, has demonstrated a comparable trend in
publication numbers from 2021 to 2023, similar to the established
European countries. This observation suggests that developed
nations in Europe and America are no longer the sole
contributors to RSV research, as developing countries are
increasingly dedicating resources to this field. These results
underscore the necessity for global collaboration, especially to
harness diverse knowledge and expertise from various regions.
Monitoring emerging trends such as citation bursts is crucial for
remaining informed about evolving areas of interest and
innovation. Additionally, these findings serve as a call to industry
practitioners to consider global partnerships for exploring
investment opportunities or expanding markets. Broadening
research across geographic boundaries enhances both expertise
and innovative potential. The global distribution of RSV research,
patterns of collaboration, and emerging trends signify a shift
towards more inclusive global engagement. These findings
FIGURE 1
Flowchart of CiteSpace bibliometric analysis.
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emphasize the urgency of broader collaborations, highlight
emerging research hubs, and suggest opportunities for researchers
and industry stakeholders to leverage diverse expertise in
addressing RSV.
3.3 Institutional distribution of RSV
research areas
Between 2014 and 2023, a total of 400 organizations will
participate in RSV-related research. China Medical University
(Shenyang, China), Chinese Academy of Sciences (Beijing China),
Zhejiang University (Hangzhou China), Tehran Medical University
(Tehran, Iran), Shanghai Jiao Tong University (Shanghai China),
Nanjing Medical University (Nanjing, China), Jiangnan University
(Jinan, China), Shahid Beheshti University of Medical Sciences
(Tehran, Iran), Consiglio Nazionale delle Ricerche (Catania,
Italy), and Fudan University (Shanghai China) are among the top
ten research organizations in terms of the number of publications
(Table 2). 7 of them belong to China, 2 to Iran, and 1 to Italy. China
Medical University (Shenyang, China) has the largest number of
publications and the most citations in this field, indicating that it is
in the leading position in RSV research. It is worth noting that
Harvard University (Cambridge, United States) has the highest
average number of citations (89.41), indicating that its research
results are widely recognized by the academic community, but it is
not among the top 10 institutions in terms of the number of
publications. Figure 4A illustrates the co-citation network of
research institutions focused on RSV. We constructed the
network of research institutions’cooperation relationship with the
threshold of ≥5 publications and divided the network into 5 clusters
according to color, the width of the connecting line represents the
FIGURE 2
(A) Pie chart of RSV research publications by country. (B) Research publications on “RSV”from 2014 to 2023 (increasing trend).
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intensity of cooperation between institutions, and the size of the
circle represents the number of institutional publications. Tehran
Medical University (Tehran, Iran) and Consiglio Nazionale delle
Ricerche (Rome, Italy) serve as the central institutions within the
yellow cluster, exhibiting numerous co-citations. Harvard
University (Cambridge, United States) leads the blue cluster in
terms of the volume of published papers and co-citations. Chinese
universities in the red cluster are notable for their substantial
publication output and strong co-citation ties, establishing a core
group with significant collaboration potential. King Saud University
(Riyadh, Saudi Arabia) and King Abdulaziz University (Jeddah,
Saudi Arabia) are pivotal institutions in the purple cluster,
characterized by numerous shared citations. Core institutions of
the green cluster include Universidade Federal do Rio Grande do
Sul (Porto Alegre, Brazil) and Universidade do Porto (Porto,
Portugal). Through an analysis of this co-citation network, we
can discern key institutions and collaborative networks in RSV
research, observe regional centralization trends among different
clusters, and uncover potential opportunities for collaboration. In
terms of inter-institutional cooperation, China Medical University,
as a leading institution, shows a strong willingness to cooperate with
other institutions. Strong links between China Medical University
(Shenyang, China) and almost all prestigious academic
organizations support this (Figure 4B). It is noteworthy that the
vast majority of these institutions show a preference for national
rather than international collaboration. Universite Paris Cite (Paris,
FIGURE 3
(A) Shows the geothermal map of symbiotic networks and cooperation. The contours of each country’s territory differentiate it, while the thickness
of the lines connecting different countries indicates the intensity of their cooperation. In addition, the color of the different countries and the size of
the circles represent the number of publications. (B) Map of the intensity of country cooperation. (C) The map displays the citation bursts of the top
5 countries, with each country’s bursts represented by red bars.
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France), Wayne State University (Detroit, United States), and the
University of Illinois System (Illinois, United States) are the top
three institutions in terms of citation bursts, unfortunately, none of
the three institutions have shown any sustained bursts in the
previous five years (Figure 4C).
3.4 Analysis of research author
collaborations in the field of RSV
Highly published and highly cited authors have a very high
contribution and influence in the field of RSV, which can provide
benchmarks and guidance for future research and help other
researchers explore emerging research areas and potential
innovations. According to Price’slaw,theformula
N=0.749×(hmax)1/2(hmax indicates the amount of literature of
the author with the largest number of publications) was used to
determine the core authors, and when the number of publications of
an author>N, the author is the core author. Following the
aforementioned screening criteria, we identified 1354 core authors
who authored a total of 12933 articles, representing 76.37% of the
total article count. This suggests that these core authors have made a
significant contribution to the majority of the RSV research
literature. In addition, Richard Tristan (Universitede Bordeaux,
France), Zhang Hao (College of Animal Science and Technology,
China), and Liu Wei (Huazhong University of Science and
Technology, China) are the three authors with the largest number
of publications, with 51, 42, and 41 articles (Table 3). These authors’
contributions emphasize their significance in the field of RSV. We
identified the core authors as those with more than 6 publications,
visualized and analyzed the collaborations among 1000 authors
with more than 10 publications, and displayed the authors’
collaborative network (Figure 5A). These authors have formed
several stable collaborative structures, and there is close
cooperation among the internal staff. However, there is a lack of
exchanges and cooperation among the different groups, and a few
TABLE 2 Top 10 organizations in the WoSCC of RSV research publications.
Number Institution Country Publications Citations Average number of citations
per article
1China Medical University China 185 4373 23.64
2Chinese Academy of Sciences China 181 4268 23.58
3Zhejiang University China 159 3711 23.34
4Tehran University of Medical Sciences Iran 147 3826 26.03
5Shanghai Jiao Tong University China 142 4144 29.18
6Nanjing Medical University China 114 2878 25.25
7Jiangnan University China 112 3250 29.02
8Shahid Beheshti University of
Medical Sciences
Iran 111 3636 32.76
9Consiglio Nazionale delle Ricerche Italy 108 3105 28.75
10 Fudan University China 108 3444 31.89
TABLE 1 Top 10 countries in the WoSCC of research publications in the RSV field.
Number Country Number of publications Number of citations Average number of citations per article
1China 5419 122969 22.69
2USA 2404 82379 34.27
3Italy 1192 34077 28.59
4India 1149 26972 23.47
5Spain 855 24772 28.97
6South Korea 789 19893 25.21
7Iran 753 18513 24.59
8Brazil 724 13692 18.91
9Japan 618 11666 18.88
10 Turkey 506 8416 16.63
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groups have not established cooperation with other groups. We
should aim to increase inter-regional exchanges and cooperation
among the researchers in the future. In the future, we should focus
on increasing cross-regional communication and cooperation
among researchers. The citation burst displays the frequency of
an author’s citations in a specificfield over a specific timeframe. We
show the top 10 authors with the highest citation frequency in their
field (Figure 5B).
Sahebkar Amirhossein (Mashhad University of Medical
Sciences, Iran) has the highest citation burst (8.52), followed by
Wang Tian (Nanjing Agricultural University, China) (citation burst
= 7.89). In addition, we noticed that authors Chen Hong (Medical
College of Chinese People’s Armed Police Forces, China), Sahebkar
Amirhossein (Mashhad University of Medical Sciences, Iran), and
Nagabhushanam Kalyanam (Sabinsa Corporation, USA) have
significantly increased the number of publications in the last three
years, which indicates that they are paying more attention to the
field of RSV and may produce more research results in this field in
the future (Figure 5C). Sahebkar Amirhossein’s research
contribution to RSV is to provide its potential application in a
variety of disease models, including diabetic nephropathy (Ghavidel
et al., 2024), neurodegenerative diseases (Keshavarz Shahbaz et al.,
2024), Parkinson’s disease (Iranshahy et al., 2022), and metabolic
disorders (Ghavidel et al., 2023). These studies have laid the
FIGURE 4
(A) Shows a co-citation network of related research institutions. Different colors indicate different clusters, and institutions with strong co-citation
relationships are clustered to generate a hierarchical graph describing these associations. The thickness of the lines between the circles indicates the
strength of cooperation between institutions, while the size of the circles represents the number of documents published by each institution.
(B) Graph of the intensity of cooperation between institutions. (C) The citation explosion of the top 10 institutions is depicted, with the red bars
representing the period during which the institutions experienced this explosion.
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foundation for the clinical application of RSV and the development
of novel treatment options.
3.5 A study of journal publications in the
field of RSV
We used the bibliometrics online analysis platform to select
journals with high publication volume and high impact in the field
of RSV, and visualized the journals and co-cited journals through
VOSviewer programming. We show the top 10 journals in terms of
publications and co-citations, and their corresponding IF
(JCR2024) and JCR numbers (Table 4). JCR Q1 and Q2 distribute
the top 10 journals, with seven of them having IF values higher than
5. The number of publications in Molecules (MDPI, Switzerland)
and International journal of molecular sciences (MDPI, Switzerland)
is more than 400, indicating that these two journals are more active
than others in the field. The highest number of publications was
FIGURE 5
(A) Shows the collaborative visualization network of authors in the RSV research area. Circles and text labels form a node where different colors
indicate different clusters. The size of the circles positively correlates with the number of articles published by the authors, while the thickness of the
lines between the circles indicates the intensity of collaboration between the authors. (B) Graph of co-cited authors. The circle’s size signifies the
number of times an author has received co-citations, while the line connecting the circles signifies the co-citation relationship within the literature.
(C) The top 10 authors with the highest number of citations in RSV-related publications.
TABLE 3 Top 10 authors in terms of the number of publications and citations.
Number Author Institution Country Publications Citations Average number of
citations per article
1Richard tristan Universitede Bordeaux France 51 1126 22.08
2Zhang hao College of Animal Science and Technology China 42 828 19.71
3Liu wei Huazhong University of Science
and Technology
China 41 971 23.68
4Mcclements
david julian
University of Massachusetts USA 41 3359 81.93
5Ho chi-tang Rutgers University USA 40 1003 25.08
6Portillo maria p. University of the Basque Country Spain 38 931 24.50
7Wan jing The Third Military Medical University China 38 904 23.79
8Tain you-lin Kaohsiung Chang Gung Memorial Hospital and
Chang Gung University College of Medicine
China 35 883 25.23
9Wang yan Capital Medical University China 35 876 25.03
10 Hamada hiroki Okayama University of Science Japan 34 283 8.32
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found in Molecules (IF = 4.6, Q2) with 440 papers, followed by
International journal of molecular sciences (IF = 5.6, Q1) (429
papers) and Nutrients (MDPI, Switzerland) (IF = 5.9, Q1) (304
papers). Molecules is an academic journal of chemistry-organic
chemistry, focusing on the frontiers of materials chemistry.
The visualization of journal citation density illustrates the
distribution of journals within a two-dimensional framework,
reflecting their citation impact (Figure 6A). Varied colors denote
distinct citation densities, with darker hues typically indicating
higher densities. Journals such as International journal of
molecular sciences,Molecules, and Nutrients exhibit the highest
citation densities. In addition, we used cluster analysis to roughly
categorize all journals into four groups (Figure 6B). The entire
network of journals is very closely and widely connected. The red
area includes journal of agricultural and food chemistry (ACS,
USA), Molecules,international journal of pharmaceutics
(ELSEVIER, UK) and so on. The yellow area contains Oncotarget
(Impact Journals), Nutrition and Cancer an international journal
(Taylor & Francis). The green cluster contains antioxidant (MDPI,
Switzerland), molecular nutrition & food research (Wiley).
Nutrients, which ranks first in the number of scientific reports,
belongs to the blue cluster. Molecules, which has the most average
citations per article, belongs to the red cluster, and the International
journal of molecular sciences, which ranks first in the number of
citations, belongs to the blue cluster.
By analyzing the clusters (Figure 6C), we can directly observe
the cooperation between journals and other information. The
journals of agricultural and Food chemistry,journal of biological
chemistry,plos one, and Nutrients (MDPI, Switzerland) are active
journals with red, yellow, blue, and green clusters respectively,
which have extensive co-citation relationships.
3.6 Analysis of highly cited literature in the
field of RSV research
In the co-cited literature network within the domain of RSV
research (Figure 7A), each cluster signifies a significant research
topic or direction, facilitating the identification of influential
studies. For instance, 2006 Joseph A Baur et al. published
Therapeutic Potential of Resveratrol: The In Vivo Evidence and
Resveratrol Improves Health and Survival of Mice on a High-
Calorie Diet. This network reveals an extensive number of
references and connections between nodes, underscoring a robust
interrelationship with other scholarly works.
VOSviewer was used to look at RSV-related literature published
from2014to2023(Table 5), and find important papers in the field by
looking at literature co-citations and citation bursts, which show how
research topics changed over time. Articles with a high number of co-
citations were considered to hold an authoritative position in the field
and were able to suggest the necessary intellectual context for the study.
2016 Hua Zhang et al. published Dietary polyphenols, oxidative stress,
and antioxidant and anti-inflammatory effects in Current Opinion in
Food Science was the most cited article (n = 618), which pointed out that
phenolic compounds, such as phenolic acids, flavonoids, and
proanthocyanidins, have protective effects against biotic and abiotic
TABLE 4 Top 10 journals with RSV research publications in WoSCC.
Number Journals IF
(2021)
IF
(2022)
IF
(2023)
JCR
(2023)
Publisher Countries Count Total
citation
Average
number
of
citations
per article
1Molecules 4.93 4.6 4.2 Q2 MDPI Switzerland 440 8701 19.78
2International journal
of molecular sciences
6.21 5.6 4.9 Q1 MDPI Switzerland 429 9537 22.23
3Nutrients 6.71 5.9 4.8 Q1 MDPI Switzerland 304 8623 28.37
4Food chemistry 9.23 8.8 8.5 Q1 ELSEVIER the
United
Kingdom
231 7755 33.57
5Scientific reports 4.38 4.6 3.8 Q2 NPG the
United
Kingdom
216 6750 31.25
6Antioxidant 7.675 7 6.0 Q1 MDPI Switzerland 208 3146 15.13
7Plos one 3.752 3.7 2.9 Q2 PLOS United States 205 7243 35.33
8Journal of agricultural
and food chemistry
5.895 6.1 5.7 Q1 ACS United States 172 4668 27.14
9Frontiers
in pharmacology
5.988 5.6 4.4 Q1 Frontiers Switzerland 167 3266 19.56
10 Food & function 6.317 6.1 5.1 Q1 The Royal
Society
of Chemistry
the
United
Kingdom
158 5723 36.22
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stresses. It summarizes the research progress on dietary polyphenols,
explores their antioxidant and anti-inflammatory activities, and
investigates their involvement in inflammation-mediated metabolic
disease mechanisms. Followed by the paper The therapeutic potential
of resveratrol: a review of clinical trials (n = 211) by Adi Y Berman et al.,
published in the journal NPJ precision oncology in 2017. A citation burst,
defined as a significant increase in the frequency of citations for a
specific reference over a specificperiod,signifies the rapid identification
FIGURE 6
(A) Visualization of journal citation density. The color intensity represents the total number of journal publications, with the more reddish color bias
representing a higher number of publications. (B) RSV network of research-related journals. Each node represents a journal. The same color
indicates that the nodes are in the same cluster. Node size and link thickness reflect the frequency of journal collaboration. (C) RSV study-related
journals co-citation network. the same color indicates that the nodes are in the same cluster. The node size reflects the frequency of journal co-
citation, and the links represent the co-citation relationship between journals, proportional to the thickness of the links.
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and dissemination of that reference within the field of study. We display
the top 25 citation surges (Figure 7B), with 16 articles receiving high
citations over a period exceeding 3 years. During the period under
investigation, a large number of widely cited articles in the field of RSV
ledtotheexplosionofcitedliterature,whichbeganin2014.Rossouw
JE’s 2012 article in Cell entitled Resveratrol ameliorates aging-related
metabolic phenotypes by inhibiting cAMP phosphodiesterases was the
most explosive article (n = 75.98). The article asserts that red wine
commonly contains RSV, a polyphenol believed to possess anti-aging
and anti-diabetic properties. It increases NAD(+) and Sirt1 activity by
competitively inhibiting cAMP-degrading phosphodiesterases, raising
cAMP levels, increasing intracellular Ca(2+) levels, and activating the
CamKKb-AMPK pathway. In addition, the metabolic benefits of RSV,
including the prevention of diet-induced obesity, improvement of
mitochondrial function, physical strength, and glucose tolerance, can
be mimicked by the PDE4 inhibitor rolipram. Thus, the application of
phosphodiesterase 4 (PDE4) inhibitors may contribute to the
prevention and amelioration of metabolic diseases associated with
aging. In recent years, cited articles have focused more on RSV’s
novel therapeutic modalities for various diseases and their molecular
FIGURE 7
(A) Graph of co-cited references. The size of the spheres represents the co-citation frequency of articles in the RSV domain, and the connecting
lines between the circles indicate the co-citation relationships in the literature. (B) The 25 most frequently cited references. The red line represents
the burst interval, indicating the start and end years of the citation explosion, as well as the burst duration. The blue timeline represents the
publication timeline, while the light and dark blue parts indicate the absence and presence of citations, respectively.
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TABLE 5 Highly cited literature with top 10 studies in RSV.
Number Title Number
of
citations
Years
of
publication
Magazine Author Article
type
Summary DOI
1Dietary polyphenols,
oxidative stress and
antioxidant and anti-
inflammatory effects
618 2016 Current
Opinion in
Food Science
Hua Zhang review
paper
Phenolic compounds such as phenolic acids, flavonoids, and anthocyanins have a
protective effect against biotic and abiotic stress. Fruits, vegetables, grains, spices, and
herbs primarily contain these compounds, and a high intake of these compounds can
reduce the risk of oxidative stress-related diseases. This paper aims to summarize the
research progress of dietary polyphenols, explore their antioxidant, anti-inflammatory,
and metabolic disease mechanisms involved in inflammation mediation, and look
forward to future research directions.
(Zhang and
Tsao, 2016)
2The therapeutic potential
of resveratrol: a review of
clinical trials
211 2017 NPJ
precision
oncology
Adi Y Berman review
paper
RSV has anti-inflammatory and antioxidant effects and has an impact on the occurrence
and development of many diseases. This paper reviews the clinical data of RSV and finds
that it performs well in nervous system diseases, cardiovascular diseases, and diabetes but
may have negative effects in some cancers and NAFLD, which provides useful guidance
for the design of preclinical and clinical studies of RSV.
(Berman
et al., 2017)
3Novel insights of dietary
polyphenols and obesity
137 2014 The Journal
of
Nutritional
Biochemistry
Shu Wang review
paper
This paper investigated the role of dietary polyphenols in the prevention of obesity and
obesity-related chronic diseases, with a special focus on green tea catechins,
epigallocatechin gallate, RSV, and curcumin. Cellular studies revealed that these
polyphenols reduce adipocyte activity, inhibit adipocyte differentiation and triglyceride
accumulation, and reduce inflammatory responses. In addition, they also affect obesity by
modulating various signaling pathways and biological processes such as adipogenesis,
antioxidants, and anti-inflammatory responses.
(Wang
et al., 2014)
4Resveratrol: A Double-
Edged Sword in
Health Benefits
129 2018 Biomedicines Bahare Salehi review
paper
This paper describes the structure of RSV, its origin, and its role in medicine. RSV, as a
polyphenolic stilbene compound, is widely found in plants, especially grape skins and
seeds, and in foods such as red wine. It has a strong antioxidant potential and
antipathogenic capacity and is considered a plant antitoxin. In addition, RSV has shown
a variety of biological activities, such as anti-tumor, anti-inflammatory, cardioprotective,
vasorelaxant, phytoestrogenic, and neuroprotective. However, its application in the
pharmaceutical field still faces challenges, including solubility, bioavailability, and
adverse effects.
(Salehi
et al., 2018)
5Applications of
nanoparticle systems in
drug delivery technology
110 2018 Saudi
Pharm J
Syed A A Rizvi review
paper
This paper explores the opportunities for nanoparticle-based drug formulation
development in addressing and treating complex diseases. By modulating size, surface
properties, and materials, nanoparticles can form smart systems that encapsulate
therapeutic and imaging agents and materials. These systems can precisely deliver drugs
to specific tissues and provide controlled-release therapies, thereby reducing drug toxicity
and improving patient compliance. Nanotechnology has made significant advances in the
treatment of diseases such as cancer and AIDS and has facilitated the development of
diagnostic tests.
(Rizvi and
Saleh, 2018)
6The effects of
polyphenols and other
bioactives on
human health
95 2019 Food
& Function
Cesar G Fraga review
paper
Different types of polyphenols may reduce the risk of various chronic diseases, e.g.,
flavan-3-ols in cocoa are associated with cardiovascular health, while the flavonoids
quercetin and stilbene RSV are associated with cardiometabolic health. Polyphenols may
also have clinical effects because they influence the gut microbiota and interact with
other phytochemicals.
(Fraga
et al., 2019)
(Continued)
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TABLE 5 Continued
Number Title Number
of
citations
Years
of
publication
Magazine Author Article
type
Summary DOI
7Curcumin, the golden
nutraceutical:
multitargeting for
multiple chronic diseases
79 2017 British
Journal
of
Pharmacology
Ajaikumar
B
Kunnumakkara
review
paper
Turmeric contains a pigment called curcumin. Numerous studies have demonstrated its
antimicrobial and anti-inflammatory activity and its positive effects on a variety of
chronic diseases, such as cancer, diabetes, and cardiovascular disease. It has anti-
inflammatory properties because it inhibits various cell signaling pathways. In addition,
curcumin has synergistic effects with other nutraceuticals.
(Kunnumakkara
et al., 2017)
8Autophagy and apoptosis
dysfunction in
neurodegenerative
disorders
72 2014 Progress
in
Neurobiology
Saeid Ghavami review
paper
Autophagy and apoptosis are crucial physiological processes that maintain cellular
homeostasis. Autophagy involves the removal of long-lived proteins and damaged
organelles, while specific morphological features mediate apoptosis. Neurodegenerative
diseases are believed to develop due to disruptions in autophagy. In this paper, we briefly
review the recent advances in autophagy in neurodegenerative diseases and introduce the
roles of autophagy and apoptosis in maintaining brain homeostasis. Finally, we discuss
the potential applications of autophagy and apoptosis regulation in the treatment of
neurodegenerative diseases.
(Ghavami
et al., 2014)
9Slowing ageing by design:
the rise of NAD+ and
sirtuin-
activating compounds
68 2016 Nat Rev Mol
Cell Biol
Michael
S Bonkowski
review
paper
SIRT1-7 is a family of NAD-dependent deacetylases with remarkable ability to prevent
disease and reverse aging. Improvements in organ function, physical endurance, disease
resistance, and longevity have been demonstrated by modifying or treating mice with
sirtuin-activating compounds (STACs) or NAD precursors. Experiments suggest that
STACs may be safe and effective in treating inflammatory and metabolic disorders in
non-human primates and humans.
(Bonkowski and
Sinclair, 2016)
10 Resveratrol Attenuates
Trimethylamine-N-Oxide
(TMAO)-Induced
Atherosclerosis by
Regulating TMAO
Synthesis and Bile Acid
Metabolism via
Remodeling of the
Gut Microbiota
53 2016 mBio Ming-
liang Chen
original
research
RSV is a natural plant antitoxin with anti-atherosclerotic effects, but its mechanism of
action is still unclear. The findings showed that RSV could lower TMAO levels and
weaken AS caused by TMAO. It did this by changing the microbiota in the gut and
stopping TMA production. RSV also increased the number of good bacteria and sped up
the release of bile acids and the elimination of feces, which changed the production of
bile acids in the liver. This process involves multiple biochemical pathways, including the
regulation of the intestinal FXR-FGF15 axis.
(Chen
et al., 2016)
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mechanisms, illustrating that RSV has demonstrated its positive effects
onhumanhealthinseveralways.The primary goal is to alleviate
diseases in various tissues by increasing antioxidant capacity and
modulating various signaling pathways. We discuss the application of
RSV composite nanoparticles in drug delivery. Preventive and clinical
measures for RSV are summarized to provide guidance for the correct
understanding of RSV, accurate diagnosis, and effective prevention and
treatment of RSV.
3.7 Analysis of research keywords in the
field of RSV
Keywords are summaries of the core content of an article and
can be used to analyze the research hotspots and frontiers in the
field of RSV. A total of 1000 keywords were obtained in this study.1
keyword had more than 10,000 occurrences, and 13 keywords had
more than 1000 occurrences. Eight of them have a total link
strength of more than 10000, and the rest of them are more than
1000. As a keyword included in the search formula, resveratrol
(11038) occupies the No. 1 position in the number of occurrences of
the keyword. Then VOSviewer was used to cluster the keywords as a
basis for summarizing the research themes and hotspots, helping
scholars to understand the direction and trend of the research focus
in the field and clarifying the relationship between different themes
in the field. The whole cluster analysis network is highly connected
with a strong co-occurrence relationship, in which many node
keywords, such as oxidative stress, apoptosis, expression,
antioxidant, activation, in vitro,inflammation, etc., play an
important role in connecting other branches of the field
(Figure 8A). The red cluster emphasizes RSV’scapacityto
function as a potent antioxidant, including antioxidants, trans-
resveratrol, and polyphenols. RSV mitigates oxidative stress-
induced damage to cells and tissues by neutralizing free radicals
and bolstering the cells’antioxidant defense mechanisms. The blue
cluster, encompassing NF-kappa B, cancer, access, and apoptosis,
highlights RSV’s potential in oncological therapies. Research in the
green clusters—oxidative stress, inflammation, SIRT1, obesity, and
diabetes—spotlights the anti-inflammatory and metabolic
regulatory properties of RSV. Lastly, investigations within the
yellow cluster—mechanics, injury, autophagy, and protection—
concentrate on RSV’s roles in cellular protection and repair.
Based on the keyword cluster analysis, we present the prominent
keywords across different years, distinguished by various colors
(Figure 8B). The keyword clusters that ignited the research surge in
the early year (2014) were mice and red wine. Keywords such as
grapes, small molecule activators, nitric oxide synthase, stilbene
synthase, human cell survival, mice, French paradox, glycosides,
heme oxygenase, and chromatography have recently diminished in
relevance. In contrast, nanoparticles, drug delivery, and gut
microbiota have seen a rise in popularity. We illustrate the
research hotspots and developmental trends of RSV through the
density of the keyword co-occurrence network (Figure 8C). By
integrating these two figures, the intensity of the color corresponds
to the frequency of occurrences. This allows us to discern the
distribution patterns of each keyword within the field.Keywords
with strong citation bursts can also reflect some emerging academic
trends and hot topics in the field and can be used to predict the
direction of cutting-edge research and reveal potential hot spots in
the field. We list the top 25 most-cited keywords (Figure 8D). Gut
microbiota exhibited the highest burst intensity related to RSV
(intensity = 23.99), followed by grapes (n = 16.91). The RSV
keyword burst is delineated into two distinct phases. In the first
phase (2014-2017), prominent keywords included grapes, small
molecule activators, nitric oxide synthase, stilbene synthase,
humans and cell survival, with additional attention. The second
phase (2020-2023) features keywords such as gut microbiota,
natural compounds, femulic acid and wound healing, reflecting
current research hotspots and emerging frontiers in the field.
4 Discussion
Commonly used analytical tools in the field of bibliometrics
include CiteSpace, VOSviewer, and Bibliometrix in R. CiteSpace
helps to discover research frontiers and hot topics by deeply
analyzing citation relationships in the literature and displaying
citation and collaboration vectors through network diagrams.
VOSviewer generates scientific maps that show links between
literature, authors, and journals, and provides impact assessment.
Bibliometrix provides functions and tools for importing, processing,
and cleansing literature data, including co-occurrence analysis,
topic modeling, and collaborative network analysis, etc., with
intuitive and easy-to-understand results. Together, these tools
provide researchers with valuable information to gain a deeper
understanding of the structure and trends of the discipline, to grasp
research hotspots, and to assess the impact of research. RSV is a
naturally occurring compound found in plants, particularly grapes,
peanuts, and certain herbs. It is thought to have antioxidant and
anti-inflammatory properties that may be beneficial in reducing the
risk of heart disease and certain cancers. To date, no studies have
been found on the bibliometric analysis of RSV. Although there are
some studies supporting the benefits of RSV, more research is
needed to confirm its effectiveness and safety. In addition,
individual differences, intake doses, and long-term use may affect
its effectiveness, so more in-depth knowledge is needed before
recommending it for health purposes.
4.1 Global contribution to RSV research
Over the past decade, we have observed a continuous increase in
academic publications in this research area. The significant increase
in research activity in this field highlights its immense research
value and may usher in new advances in the future. Papers were
mainly published in Asian, North American, and European
countries, with China having the highest number of publications
related to economic development and the government’s emphasis
on research. The United States follows China, with a strong
collaborative relationship between the two countries.
Nevertheless, the research on RSV is still insufficient, and
international cooperation is particularly important to pool
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FIGURE 8
(A) Keyword clustering visualization The size of the circles is positively correlated with the frequency of keyword occurrences. The thickness of the
connecting lines between the circles is related to the strength of the relationship between the keywords. Nodes of different colors form different
clusters, and each color represents a different research direction. A co-occurrence clustering algorithm is performed on the keywords by calculating
the keyword similarity to cluster the keywords with high similarity. (B) Keyword Strength Visualization Temporal Overlay. The size of the circle
corresponds positively to the frequency of keyword occurrences. The average year of occurrence of each keyword is indicated by the gradient in
the lower right corner. Blue indicates keywords with earlier occurrences, and red indicates more recent occurrences that may evolve into new
research directions. (C) Keyword density visualization plot. The depth of color is proportional to the frequency of keyword occurrences. (D) The top
25 most frequently cited keywords in CiteSpace.
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technology and resources to solve technical problems, promote the
development of the RSV preparation process, and advance the field
of Chinese medicine.
4.2 Research progress of RSV
In 1939, Japanese scientist Takaoka extracted RSV from the
rhizome of the toxic plant Veratrum grandiflorum (Takaoka, 1939).
RSV was first synthesized by Spath and Kromp using Perkin
reaction in 1941 (Späth and Kromp, 1941). Studies on its
antioxidant and health effects began in the 1980s, but did not
attract widespread attention. In 1985, Moreno-Manas et al. used 3,
5-dihydroxytoluene as the starting material to prepare RSV through
Wittig reaction, which had the disadvantages of low yield, low
selectivity of ciso isomerism, and difficult to remove triphenyl
phosphorus oxide as a by-product (Moreno and Pleixats, 1985).
In the 1990s, researchers in Connecticut discovered RSV in wine
(Jeandet et al., 1995). Sparked a global research boom. In 1997, RSV
was confirmed to have anticancer activity (Jang et al., 1997). In
2003, Jeffery and Ferber successfully synthesized RSV by palladium-
catalyzed one-pot method with a total yield of 80%. In recent years,
this method has been widely concerned and has become the most
promising method (Jeffery and Ferber, 2003). In 2003, Nature
published a paper that RSV extended the life of yeast (Howitz
et al., 2003), and in 2004 reported that RSV had a very clear effect on
extending cell life (Wood et al., 2004). In 2006, its life-prolonging
effect was demonstrated in mice (Baur et al., 2006). In 2008, Cell
Metabolism revealed that RSV may affect the aging and health of the
body (Pearson et al., 2008). After 2010, despite mixed research
results and fraud scandals, RSV’s health benefits remain unproven.
In 2012, Cell analyzed the molecular mechanism of RSV’s
promotion of human health (Tennen et al., 2012). And RSV
improved the metabolic phenotype associated with aging by
inhibiting cAMP phosphodiesterase (Park et al., 2012). RSV is
commercialized as a food and cosmetic ingredient and is sold as a
food supplement. The current market is approximately $97.7
million and is expected to grow at a compound annual growth
rate of 8.1% from 2018 to 2028 (Saez-Saez et al., 2020).
4.3 Research hotspots and frontiers of RSV
Keyword analysis plays a crucial role in the field of scientific
research, not only reflecting the current research hotspots but also
predicting the future development direction. From the latest
keyword analysis data, we observe that the term “nanoparticle”
has become the most popular research topic. This trend indicates
that in future research, the combination of nanoparticles and RSVs
will become a new trend. Topical application of nanomedicines can
deliver therapeutic drugs directly into target tissues to exert
therapeutic effects, and it is simple and easy to implement (Li
et al., 2021b). Nano-formulated RSV effectively and significantly
slowed the growth of colon cancer cells and the amount of
hemoglobin in the tumor volume. It did this while remaining
more bioavailable and effective (Sudha et al., 2020). When we
combine nanoparticles and RSVs, we expect breakthroughs in
drug discovery and disease treatment. The keyword “delivery”
follows “nanoparticle.”In the field of drug delivery, nano-
preparations such as nanoparticles and liposomes have
demonstrated their importance in targeted therapy. Researchers
have shown that solid lipid nanoparticles and nanostructured lipid
carriers may be able to improve RSV’s low bioavailability and low
ability to dissolve in water (Chimento et al., 2019). These
nanoparticles have the unique advantage of improving drug
stability and, in some cases, drug release (Kianfar, 2021). Studies
have demonstrated that nanoparticles have been used to target RSV
delivery to the brain, proving highly beneficial for treating
neurological conditions such as cerebral hemorrhage (Mo et al.,
2021). In particular, lipid nanoparticles, when functionalized with
apolipoprotein E, can prevent the degradation of RSV in the
bloodstream and achieve precise brain-targeted delivery (Neves
et al., 2016). In addition, Wang et al. utilized a polylactic acid-
hydroxyacetic acid copolymer to create inhalable RSV inclusion
nanoparticles, which targeted drug concentration in the lungs and
significantly enhanced RSV’s anticancer efficacy against non-small
cell lung cancer (Qiu et al., 2020). Liposomes, as an innovative drug
delivery system, offer numerous benefits including minimal adverse
effects, high bioavailability, and effective targeting (Pandita et al.,
2014). The RSV-loaded liposomes developed by Wiedenhoeft et al.
were adept at delivering RSV to the cerebral microcirculation,
mitigating oxidative stress in cerebral microvessels and thus
safeguarding them (Wiedenhoeft et al., 2019). Nanocapsules have
been found to be chemically multifunctional, which can not only
improve the antioxidant activity and stability of drugs (Liu et al.,
2020), but also deliver drugs in a targeted manner (Amin et al.,
2018). RSV-loaded nanocapsules can traverse the blood-brain
barrier, elevating RSV levels in brain tissue and providing
neuroprotective effects in AD rats (Frozza et al., 2013). Moreover,
encapsulating RSV in filipin protein nanoparticles allows for
controlled drug release, enhancing drug stability and preventing
unnecessary metabolic degradation, thus improving RSV’s ability to
promote wound healing and extend its therapeutic duration
(Lozano-Perez et al., 2017).
The application of RSV in topical therapy is limited due to its
low bioavailability and poor water solubility when taken orally
(Valachovaand Soltes, 2021). Natural multicapsular compounds
such as gellan gum, gelatin and pectin can form stable networks in
acidic environments, but gellan gum is susceptible to high
temperatures and has poor water solubility (Prezotti et al., 2020).
The addition of RSV can reduce the attraction between carboxyl
groups, thus reducing the swelling degree of the hydrogel and
promoting the release of RSV (Wang et al., 2021). The
combination of oils and polysaccharides formed heterogeneous
hydrogels, which prolonged the active time of the drug in the
blood and improved stability and bioavailability compared to free
RSV (Joseph et al., 2022). High molecular weight chitosan protects
RSV from UV degradation through the formation of nanogels and
is further encapsulated in nuclear endosomes for improved
targeting after cellular internalization (Buosi et al., 2020). Despite
the poor mechanical strength of chitosan hydrogels, hydrogels
constructed using bioactives have received attention in recent
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years, and the porous nanostructures formed by peptide moieties
not only have good mechanical strength, but also provide a natural
bioenvironment for RSV to exhibit excellent slow-release properties
(Zhao et al., 2020).
In 2023, gut microbiota, natural compounds, wound healing, and
other keywords will still maintain a strong explosive trend. The gut
microbiota is increasingly recognized as a promising target for the
treatment and prevention of inflammatory and metabolic disorders in
humans (Bastos and Rangel, 2022). As a low molecular weight stilbene
compound, RSV is predominantly metabolized in the large intestine,
where it influences the gut microbiota. During its metabolism, RSV
exits the gut through transporter proteins such as breast cancer
resistance proteins and enters systemic circulation via multidrug
resistance protein 2 (MRP2) on theapicalmembraneandMRP3on
the basolateral membrane (Abdelhafizetal.,2023). Approximately 70-
75% of RSV undergoes metabolism in the gut, with only 1-8% entering
the bloodstream (Vesely et al., 2021). The villi play a crucial role in
nutrient absorption and transport. Research indicates that RSV
supplementation can enhance intestinal morphology (Qiu et al.,
2021), including increasing jejunal villus height and length in mice
with non-alcoholic fatty liver disease (NAFLD) (Wang et al., 2020a).
Alterations in the composition of the intestinal microbiota have been
linked to the onset and progression of numerous diseases,
encompassing a variety of chronic conditions (Cai et al., 2020).
In the colon, the intestinal microbiota can further metabolize
RSV and its metabolites, with dihydroresveratrol being the most
common metabolite (Springer and Moco, 2019). The RSV
treatment was able to raise the numbers of good bacteria, like
Bifidobacteria and Lactobacilli, and lower the numbers of bad
bacteria, like E. coli and Enterobacteriaceae (Larrosa et al., 2009).
Researchers also found that RSV improved renal function,
improved glucose homeostasis, restored intestinal permeability,
and reduced the drive for inflammatory markers (Cai et al.,
2020). Specifically, RSV significantly inhibited gut microbiota
abnormalities induced by a high-fat diet, increased the growth of
beneficial bacteria, and enhanced the diversity of gut microbiota,
thereby preventing intestinal dysbiosis (Yi et al., 2014).
4.4 Clinical application of RSV
We discovered that terms with significant persistence include
“drug delivery,”“antioxidant,”and “inflammatory.”Not only does
the research in these domains have a strong basis, but it also
continues to be valuable and interesting. In particular, research on
anti-inflammatory and anti-oxidative stress is important in revealing
disease mechanisms, developing novel drugs, and so on. RSV can
down-regulate the expression of the inflammatory factors IL-1b,IL-6,
IL-8, and TNF-ain a dose-dependent manner (Li et al., 2021c). In
addition, RSV possesses strong antioxidant activity and can prevent
cellular oxidative stress by targeting and regulating the PI3K/AKT
and Wnt/b-catenin signaling pathways, increasing antioxidant
content, and decreasing the production of ROS and the marker of
oxidative stress, malondialdehyde (MDA) (Bahar and Singhrao, 2021;
Li et al., 2021c).RSV prevents oxidative stress in cells by inhibiting
signal transduction, signal transducer, and activator of transcription 1
(STAT1) (Li et al., 2021a), and activating the SIRT1/NF-kBsignaling
pathway (Yang et al., 2021a;Zhao et al., 2021)to reduce cellular
inflammation and oxidative stress. According to Wang et al (Wang
et al., 2020b), RSV reduced neuropathic pain by controlling the
expression of triggering receptors on myeloid cells. This stopped
microglia from causing neuroinflammation.
RSV features a 4′-hydroxyl group and exhibits intrinsic
biocompatibility and non-cytotoxicity (Ma et al., 2021). Currently,
the research hotspots for RSV mainly focus on its pharmacological
effects, synthesis methods, and molecular mechanisms. The compound
possesses anti-tumor, anti-inflammatory, antibacterial, and
neuroprotective characteristics, among others, and a thorough study
ofitsmechanismsofactionandtargetsisnecessary.Itsextraction,
purification, and preparation processes are also hot spots for research.
Current research focuses on investigating the molecular mechanism of
RSV’s pharmacological effects, particularly its anti-inflammatory and
antioxidant mechanisms. Further investigation into the
pharmacological and toxicological properties of RSV is necessary, as
these aspects play a crucial role in the development of new drugs,
thereby bolstering their clinical application. We should further study
RSV, a common component in many traditional Chinese medicines,
and explore its pharmacological mechanism of action to gain a deeper
understanding of its role in traditional Chinese medicine therapy.
RSV has inhibitory effects on a wide range of cancer cells, while
at the same time, it has no toxicity or side effects on normal cells.
Novel targets and pathways continue to be identified. Wu et al.
demonstrated that RSV primarily inhibits the proliferation of breast
cancer cells by interfering with the cell cycle and inducing apoptosis
(Wu et al., 2019). RSV inhibits the enhancer of zeste 2 (EZH2)
through dephosphorylation of extracellular regulated protein
kinases (ERK1/2), thereby curbing the proliferation and growth of
breast cancer cells (Hu et al., 2019). Furthermore, RSV regulates the
E2/ERa/NGB signaling pathway (Cipolletti et al., 2019),
microRNAs (Zhang et al., 2019), and the Notch pathway to
inhibit breast cancer cell proliferation. RSV also modulates the
expression of programmed cell death-ligand 1 (PD-L1) via the Wnt
pathway, where Sirtuin 1 (SIRT1) deacetylates and stabilizes
transcription factors, inhibiting Axin2 transcription and
promoting T cell factor (TCF) binding to the PD-L1 promoter
(Yang et al., 2021b). In RSV-treated HCT116 cells, transforming
growth factor beta-3 (TGF-b3) and tumor necrosis factor beta
(TNF-b) expressions are notably reduced, alongside down-
regulation of p65-NF-kB(Buhrmann et al., 2020). Buhrmann
et al. were the first to show that TNF-b/TNF-b-receptor signaling
regulates rectal cancer cell proliferation (Buhrmann et al., 2019b),
with RSV down-regulating this inflammatory response and
modulating NF-kB and focal adhesion kinase (FAK) to control
rectal tumor cell growth (Buhrmann et al., 2019a), proliferation,
and invasion. RSV and leucotaxol elevate PD-L1 expression in
rectal cancer through NF-kB signaling mediated by histone
deacetylase 3 (HDAC3)/p300, enhancing rectal cancer cell
apoptosis (Lucas et al., 2018). RSV not only independently
inhibits cancer cells but also augments the effects of drugs like
rapamycin (Bian et al., 2020) and retinoic acid (Li et al., 2018).
When combined with rapamycin, RSV inhibits tumor growth by
modulating the PI3K/AKT/mTOR signaling pathway (Bian et al.,
Wei et al. 10.3389/fpls.2024.1423323
Frontiers in Plant Science frontiersin.org18
2020). Additionally, RSV decreases galectin-3 (GAL-3) levels by
raising miR-424-3p, thereby inhibiting glycolysis and targeting the
AMPK/mTOR signaling pathway to suppress ovarian cancer cell
proliferation and induce apoptosis (El-Kott et al., 2019). Hao et al.
found that RSV might reduce inflammation through the AMPK/
Drp1 signaling pathway, thus alleviating bone cancer pain in rats
(Hao et al., 2020).
As a natural phytoestrogenic agent, RSV acts as an estrogen
receptor (ER) agonist, up-regulating vitamin D receptor expression
in osteoblasts and promoting bone formation. In postmenopausal
women, regular RSV supplementation significantly reduces CTX
levels, enhances lumbar spine and femoral neck bone mineral
density (BMD), and improves bone mineralization, with increased
osteocalcin levels mitigating bone loss (Wong et al., 2020). RSV also
shows potential as a therapeutic agent for neurodegenerative
diseases such as Alzheimer’s and Parkinson’s diseases. Research
indicates that RSV may exert neuroprotective effects in Alzheimer’s
disease models through Sirt1 signal transduction (Ma et al., 2019).
Kong et al. revealed that RSV enhances antioxidant capacity and
estrogen levels in Alzheimer’s disease models via the Nrf2/heme
oxygenase-1 (HO-1) signaling pathway (Kong et al., 2019).
Furthermore, RSV exhibits antibacterial and antiviral properties.
Huang et al. discovered that RSV significantly down-regulates MEK1/2
and ERK phosphorylation in rotavirus-infected mouse models,
alleviates diarrhea, and markedly reduces the mRNA expression
levels of IL-2, IL-10, TNF-a, interferon-g,macrophageinflammatory
protein 1, and monocyte chemoattractant protein 1 in intestinal
tissues, demonstrating its antiviral activity (Huang et al., 2020).
4.5 Research on drug development of RSV
In mammalian experimental models, RSV undergoes extensive
metabolism and rapid elimination, leading to limited bioavailability.
Following oral administration, RSV is absorbed at the intestinal level
through passive diffusion or membrane transport proteins and
subsequently released into the bloodstream, where it can be identified
either as an unmodified compound or a metabolite (Varoni et al., 2016;
Chimento et al., 2019). Despite 75% of RSV being absorbed orally, only
1% is detected in plasma after complete metabolism (Walle, 2011).
Although RSV has the disadvantages of low bioavailability, poor water
solubility, and rapid hepatic and intestinal metabolism, these problems
can be solved or ameliorated by improved co-solvents and the use of
nanoparticles, etc (Rizvi and Saleh, 2018). RSV can be absorbed in large
quantities by intestinal cells by passive diffusion or carrier-mediated
translocation across the apical membrane of the cell after oral
administration and is then metabolized rapidly and extensively to
RSVglucuronidesorsulfatesalts(Yu et al., 2002). Studies have
shown that a large proportion of ingested RSV (approximately 90%)
reachesthecoloninanintactformandundergoes subsequent intestinal
fermentation. When absorbed through the portal vein, the resulting
polyphenol metabolites will enter the liver for further methylation,
glucuronidation, or reaction with sulfate. Subsequently, the metabolites
penetrate the circulation and reach the target tissues and cells to exert
their biological activity. The bile can recycle excess RSV and its
metabolites back to the small intestine, while the urine can excrete
them (Springer and Moco, 2019). Recently, various methodological
strategies and synthetic derivatives have been developed to improve
RSV’s bioavailability. Numerous studies have focused on synthesizing
novel and more potent RSV analogs with enhanced pharmacokinetic
properties, reduced toxicity, and minimal side effects. Methoxylated,
hydroxylated, and halogenated RSV derivatives have been particularly
investigated due to their advantageous biological activities and improved
oral bioavailability (Nawaz et al., 2017). Prior research indicates that
methoxylation enhances metabolic stability and prolongs the duration
required for the molecule to attain peak plasma concentrations (Ferraz
da Costa et al., 2020).
In terms of enhancing wound healing, RSV fosters angiogenesis
and suppresses inflammation (Huang et al., 2019;Zhao et al., 2020).
However, its hydrophobic nature results in limited in vivo delivery
efficiency (Jeandetetal.,2021). To address this, a variety of advanced
wound dressings have been developed, such as hydrogels (Yang et al.,
2022) and biological scaffolds (Poornima and Korrapati, 2017), which
effectively preserve RSV’s biological activity and facilitate integration
with adjacent tissues. Researchers have created an electrospun scaffold
incorporating RSV using polycaprolactone (PCL) and a chloroform-
dimethylformamide solvent mixture, which accelerates wound closure
and re-epithelialization (Lakshmanan et al., 2019). The subsequent
application of a double-layer stent combined with hydrogel has further
augmented hemostasis and reduced swelling (Ma et al., 2021).
Additionally, studies indicate that integrating RSV with bacterial
cellulose promotes re-epithelialization of rat epidermis (Meng et al.,
2019). Furthermore, RSV-loaded nanovesicles combined with wafers
extend the drug’s residence time in the skin (Amanat et al., 2020).
Vesicles containing RSV and gallic acid exhibit potent antioxidant and
antibacterial properties, effectively shielding the skin from
environmental pollutants and damage (Vitonyte et al., 2017).
Researchers conducted pharmacokinetic studies to investigate the
pharmacokinetic properties of RSV in vivo, including absorption,
distribution, metabolism, and excretion, to provide theoretical support
for its rational use. In the meantime, researchers can explore drug
interactions, including their synergistic and antagonistic effects, to guide
the rational combination of clinical medications. Future studies can
establish quality control methods for RSV, such as fingerprinting,
content determination, and purity testing, to ensure the quality and
safety of Chinese medicine products. In the meantime, researchers can
develop novel pharmaceutical formulations of RSV, such as oral,
injection, and topical formulations, to enhance the bioavailability and
efficacy of RSV. Researchers have discovered various types of RSV
formulations and carriers. Many new things have been made, such as
RSV self-microemulsifying tablets (Bolko Seljak et al., 2018), trans-RSV
nanohybrids (Singh et al., 2017), microcapsules (Luzardo-A
lvarez et al.,
2019), poly (-caprolactone) microcapsules, and RSV liposomes
(Wiedenhoeft et al., 2019). These formulations and carriers were able
to improve the solubility, stability, bioavailability, and antioxidant and
anti-inflammatory properties of RSV.
5 Conclusion
The citation analysis was performed using CiteSpace software,
which generated a network diagram showing the research landscape
Wei et al. 10.3389/fpls.2024.1423323
Frontiers in Plant Science frontiersin.org19
in a visual way. The graph details citation relationships, co-
authorships, and other relevant metrics between different
publications, thus providing insight into the structure and trends
of the research landscape. This study focuses on analyzing the
literature related to RSV in the WoSCC between 2014 and 2023. In
addition to CiteSpace, software such as VOSviewer was used to
quantitatively visualize the number of publications, authors,
countries, and research institutions. This study analyzes in detail
the development of RSV research. According to the study, the
number of RSV-related articles on WoSCC has shown a continuous
growth trend, with an average of about 1693.4 articles being
published each year, and the overall trend has been on the rise. In
particular, China has published the largest number of papers in this
field of research, reaching 5,877, while China Medical University is
one of the institutions with the highest number of published papers
and citations in this field. In addition, the research team is mainly
led by Prof. Richard Tristan. The most published papers were
Molecules, which is an academic journal of chemistry-organic
chemistry, focusing on the frontiers of materials chemistry.
Dietary polyphenols, oxidative stress, and antioxidant and anti-
inflammatory effects is the most frequently cited article (Zhang
and Tsao, 2016). Keywords such as oxidative stress, apoptosis, and
gene expression play a key role in connecting the field to other
branches. These results highlight hot spots and important directions
in the field of RSV research. Future research challenges include how
to alter the structure of RSV to obtain derivatives with higher
bioactivity and bioavailability. The number of people focusing on
RSV research is expected to increase with the rise of emerging
disciplines and specialties. Research on nanoparticles, drug delivery,
and the gut microbiota is also becoming of increasing interest.
Future research should focus extensively on the pharmacological
effects of RSV, including antioxidant, anti-inflammatory, and
anticancer aspects, as well as its specific components and molecular
mechanisms. With the help of currently available research results,
drugs can be optimized by means of nanomaterial drug delivery to
improve their efficacy, and increase their bioavailability. These studies
support subsequent in vitro and in vivo preclinical studies, laying a solid
foundation for drug development and clinical translation. In-depth
studies of the pharmacology, toxicology, and pharmacokinetics of
RSVs will provide a better understanding of their mechanism of
action and support future medical advances.
6 Strengths and limitations
The field of RSV research is rapidly developing, with a variety of
research hotspots and a promising future. These analyses aimed to
explore the international distribution pattern of RSV research,
collaborative relationships among researchers, and major research
directions in the field. This study will help advance the field of RSV
and provide direction and lessons for future research. This work
uses the WoSCC as its primary data source and rigorously restricts
the screening to English literature following a careful review and
search of the literature. This change entails the disregard of non-SCI
publications and literature published in languages other than
English, even though its goal is to concentrate more intently on
excellent research published in SCI-indexed journals. While
CiteSpace and VOSviewer are valuable visualization tools for
literature combing, they are not a perfect substitute for a
methodical literature search procedure. This could add some
material that isn’t very relevant to the subject throughout the
literature screening procedure, which could skew the conclusions
of the analysis as a whole. However, given that these effects are
relatively small, they are unlikely to change the main trends and
characteristics revealed by the research subject.
This paper restricts the literature inclusion timeline to the end
of 2023 in order to capture the immediate dynamics of research
hotspots and frontiers. However, it is worth noting that due to the
relatively short publication period of the literature in 2023, sufficient
citation data has not yet been accumulated, which may weaken the
persuasiveness of our findings to some extent. As such, this factor
must be properly taken into account when interpreting the
analysis’sfindings. Despite these drawbacks, the study offers a
clear picture of the state of RSV today and in the future.
Data availability statement
The original contributions presented in the study are included
in the article/supplementary material. Further inquiries can be
directed to the corresponding author.
Author contributions
HW: Conceptualization, Data curation, Writing –original draft,
Writing –review & editing. GF: Formal analysis, Writing –review &
editing. WS: Data curation, Writing –review & editing. HC:
Visualization, Writing –review & editing. RD: Writing –review
& editing. YH: Funding acquisition, Writing –review & editing.
Funding
The author(s) declare that financial support was received for the
research, authorship, and/or publication of this article. This study
was funded by Shandong Taishan scholar project (tsqn202211354),
and Qian Qiuhai national famous old traditional Chinese Medicine
expert inheritance studio (National Traditional Chinese Medicine
Renjiao Letter (2022) No. 75).
Acknowledgments
This is a short text to acknowledge the contributions of specific
colleagues, institutions, or agencies that aided the efforts of the authors.
Conflict of interest
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be
construed as a potential conflict of interest.
Wei et al. 10.3389/fpls.2024.1423323
Frontiers in Plant Science frontiersin.org20
Publisher’s note
All claims expressed in this article are solely those of the authors
and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the
reviewers. Any product that may be evaluated in this article, or
claim that may be made by its manufacturer, is not guaranteed or
endorsed by the publisher.
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