Analysis of phenolic compounds in Parkinson’s disease: a bibliometric assessment of the 100 most cited papers
José Messias Perdigão1 
Bruno José Brito Teixeira1 
Daiane Claydes Baia-da-Silva2 
Priscila Cunha Nascimento2 
Rafael Rodrigues Lima2 
Herve Rogez1*- 1Centre for Valorization of Amazonian Bioactive Compounds, Federal University of Pará, Belém, Brazil
- 2Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
Objective: The aim of this study was to identify and characterize the 100 most cited articles on Parkinson’s disease (PD) and phenolic compounds (PCs).
Methods: Articles were selected in the Web of Science Core Collection up to June 2022 based on predetermined inclusion criteria, and the following bibliometric parameters were extracted: the number of citations, title, keywords, authors, year, study design, tested PC and therapeutic target. MapChart was used to create worldwide networks, and VOSviewer software was used to create bibliometric networks. Descriptive statistical analysis was used to identify the most researched PCs and therapeutic targets in PD.
Results: The most cited article was also the oldest. The most recent article was published in 2020. Asia and China were the continent and the country with the most articles in the list (55 and 29%, respectively). In vitro studies were the most common experimental designs among the 100 most cited articles (46%). The most evaluated PC was epigallocatechin. Oxidative stress was the most studied therapeutic target.
Conclusion: Despite the demonstrations in laboratorial studies, the results obtained point to the need for clinical studies to better elucidate this association.
1. Introduction
Parkinson’s disease (PD) is characterized by neurodegeneration and the presence of Lewy bodies, formed by α-synuclein (α-syn) fibrils, in the dopaminergic neurons (DNs) of the pars compacta of the substantia nigra of the brain (Balestrino and Schapira, 2020).
More than 10 million people worldwide are affected by PD. The prevalence of PD is approximately 0.3% in the general population, but this percentage increases to 1 and >4% in adults over 50 and 65 years, respectively (Balestrino and Schapira, 2020). The sum of the prevalences of PD in the 15 most popular nations in the world could reach 9 million people in 2030, approximately double the current prevalence, owing to population aging and advances in the treatment of PD (Dorsey et al., 2007).
The increase in prevalence influences the increase in the costs of the disease (Dorsey et al., 2007). Direct and indirect costs of PD are derived from drug and nondrug treatment, the payment of social security, the loss of productivity and income, hospitalizations, and laboratory tests. In the USA, the cost of the PD reached approximately USD 52 billion per year (Marras et al., 2018) while in Europe, the cost reached EUR 13.9 billion in 2010 (Gustavsson et al., 2011). In Japan, the direct cost per patient was approximately USD 37,994, and the indirect cost was approximately USD 25,356 (Yamabe et al., 2018).
Current drug treatment for symptom reduction or control includes dopaminergic pharmacological targets such as L-dopa; catechol-O-methyltransferase inhibitors; monoamine oxidase type B inhibitors (MAO-BIs); dopamine (DA) agonists; and non-dopaminergic pharmacological targets such as istradefylline, safinamide, clozapine, and amantadine (Poewe et al., 2017).
Unfortunately, the treatment of PD has side effects, such as impulsive and compulsive behaviors, nausea and hallucinations, due to the hyperstimulation of dopaminergic receptors and the serotonergic and cholinergic systems, which results in disturbances in the limbic and frontal cortical structures. In addition to side effects, drug treatment does not prevent disease progression (Connolly and Lang, 2014).
This fact has motivated the search for new substances and the development of neuroprotective drugs that prevent the death of DNs and delay the progression of the disease while causing fewer side effects (Reglodi et al., 2017). Furthermore, investing in treatments that delay disease progression by up to 20% could result in monetary benefits of USD 60,657 per patient (Johnson et al., 2013).
In this context, MAO-BIs (rasagiline and selegiline; Smith et al., 2015), coenzyme Q10 (Flint Beal et al., 2014), creatine monohydrate (Kieburtz et al., 2015), monoclonal antibodies directed against different parts of α-syn (Bergström et al., 2016), tocopherol, vitamin C (Etminan et al., 2005), docosahexaenoic acid (Cieslik et al., 2013) and phenolic compounds (PCs) have been gaining attention through demonstrations of their neuroprotective properties.
PCs are secondary plant metabolites that have at least one hydroxyl linked to an aromatic ring in their chemical structure, and they are synthesized by two metabolic pathways: the shikimate and/or acetate pathways (Cheynier et al., 2013). PCs can be classified according to their chemical structure mainly into flavonoids, phenolic acids, lignans, and stilbenes (Vuolo et al., 2018).
PCs can act on cellular mechanisms that cause DN degeneration through the modulation of gene expression and the activation of antioxidant enzymes regulated by the nuclear factor erythroid 2-related factor 2 (NrF2) pathway, thus suggesting great neuroprotective potential for PD (Magalingam et al., 2015; Hussain et al., 2018; Kujawska and Jodynis-Liebert, 2018).
The number of citations is a bibliometric parameter that indirectly indicates quality, impact, productivity and prestige (Baldiotti et al., 2021). Bibliometric analysis makes it possible to identify the most cited articles and, based on that, characterize the scientific production in the area of interest (Karobari et al., 2021). Bibliometric analyses on PD have already been performed (Li et al., 2008; Bala and Gupta, 2013; Robert et al., 2019; Pajo et al., 2020), but the role of PCs has not been addressed.
The identification and characterization of scientific production through bibliometric parameters could contribute to the understanding of the development and direction of research on PD and PCs. Thus, this study aimed to identify and characterize the 100 most cited papers on PCs in PD.
2. Materials and methods
2.1. Search strategy and database
The paper search was carried out using the Web of Science Core Collection (WoS-CC). The search terms are detailed in Table 1.
Table 1. Search strategy.
Papers published up to June 2022 were searched with no restriction for language, publication year range, or methodology selection. Two researchers independently selected papers until the 100th most cited paper was found. Disagreements were resolved by the concordance method.
2.2. Data extraction
The articles were selected based on the following inclusion criteria: the words PD or PCs or their synonyms (Table 1) were present in the title and/or abstract and/or keywords, tests were carried out only with PD models, tests were carried out with natural PCs, and pure PCs or the major PCs (in the case of extracts) were identified and quantified. Conference papers and editorial papers were excluded.
The 100 most cited papers list was compiled in descending order based on the number of citations in the WoS-CC. In the event of a tie, the ranking was based on the highest citation density (the number of citations per year).
The article citation count, article title, publication year, study design, names of authors, the continent and country of origin, keywords, tested PC, tested therapeutic target and results of the top 100 most cited articles were recorded. The country of origin was determined by the published corresponding address.
2.3. Statistical analysis
Descriptive statistical analysis of the data extracted as described in the previous section was performed using the number of citations as the main variable. MapChart was used to represent the number of publications by country and continent. Articles were grouped according to the year of publication in 3-year periods.
Study designs were classified as follows: bibliographic studies, laboratory studies (in vitro, in vivo, in situ, and ex vivo) and observational studies. Furthermore, compounds were classified according to the subclass determined in the Phenol Explorer database (Rothwell et al., 2013).
2.4. Quantitative and qualitative analysis
Visualization of Similarities Viewer (VOSviewer) software was used to generate coauthor ship and author keyword co-occurrence cluster maps (van Eck and Waltman, 2010).
The analysis units used were author name in the coauthor ship cluster maps and author keyword in the co-occurrence networks. Author names were linked to each other based on the number of joint authors, and author keywords were linked by occurrence. Units were included when they appeared in at least one of the 100 most cited articles in both networks.
The terms were organized into clusters, with each cluster represented by a color. More important terms had larger circles, and strongly related terms were positioned close to each other. Moreover, lines were drawn between items to indicate relations, with thicker lines indicating a stronger link between 2 items (van Eck and Waltman, 2010).
3. Results
Through the search strategy used (Table 1), 2,273 articles were obtained. After listing the articles in descending order on the basis of the number of citations, 530 articles were screened by the eligibility criteria, of which 420 articles were excluded for not directly addressing PD and/or PCs (the titles of excluded articles can be found in the Supplementary material; Supplementary Table), resulting in the 110 most cited articles on PD and PCs. The 110 most cited articles were ranked from highest to lowest citation number. The first 100 articles were selected to compose the bibliometric analysis (Figure 1). The 100 most cited articles were ranked based on the number and density of citations in WoS-CC. The list of all articles and the data extracted for carrying out the bibliometric analysis are shown in Table 2.
Figure 1. Methodological flowchart of the search, evaluation and selection of the most cited articles on PD and PC. The search for articles was carried out in WoS-CC, the retrieved articles were sorted in descending order based on the citation number in WoS-CC. The articles were evaluated with the eligibility criteria. Articles that did not address only PD and CP were excluded, as well as articles that did not address natural CP. 100 articles were selected and the necessary data for bibliometric analysis were extracted. Data were analyzed quantitatively and qualitatively using descriptive statistics. Software with VosViewer and Mapchart contributed to illustrate the results of the bibliometric analysis.
Table 2. The 100 most cited articles on Parkinson’s disease and phenolic compounds.
3.1. Oldest, newest and most cited article
The article “Green tea polyphenol (−)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. Journal of Neurochemistry. 2001 Sep; 78 (Yamabe et al., 2018): 1073–1082” is the most cited (434 citations) and the oldest on the top 100 list in the WoS-CC.
Additionally, on the same criteria, the most recent article on the list is “Healthspan Maintenance and Prevention of Parkinson’s-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans. International Journal of Molecular Sciences, 2020, 21,” with 53 citations.
3.2. Authors who contributed to the 100 most cited articles
The top 100 most cited articles were contributed by 497 authors forming 66 clusters (Figure 2). The major contribution with number of paper was made by a Fink, A. L. (n = 5) followed by Lee, S. M. Y.; Zhang, Z. J.; Zhao, B. L. (n = 4), followed by Datla, K. P.; Dexter, D. T.; Du, G. H.; Essa, M. M.; Haleagrahara, N.; He, G. R.; Le, W. D.; Levites, Y.; Li, G. H.; Li, X. X.; Mandel, S.; Manivasagam, T.; Martinoli, M. G.; Mu, X.; Uversky, V. N.; Xu, B.; Youdim, M. B. H. (n = 3). The other authors contributed ≤2 papers.
Figure 2. VOSviewer co-authorship map demonstrating the bibliographic coupling between the 497 authors of the 100 most cited articles on PD and PCs. The authors form 66 clusters. The cluster size represents the frequency of publications. The color scale represents the period in which the publications occurred. Overlapping nodes does not allow viewing the name of all authors who contributed to the 100 most cited articles. Authors with the highest number of publications are superimposed on authors with the lowest number of publications.
The cluster with the most authors is formed by Lee, S. M. Y. and more 19 researchers. Collaborations carried out in 2012 produced more articles, as can be seen by the thickness of the lines between authors who are present in that period of time, for example Lee, S. M.Y. and Zhang, Z. J. Figure 3A in addition, these authors received more citations, as can be seen in the heat map (Figure 3B).
Figure 3. The cluster with the highest number of publications. (A) The cluster is composed of 20 authors. The period of publication of the cluster’s papers is indicated by the color scale that varies from blue (2012) to yellow (2015). The node size represents the citation number of each author. The authors who collaborated in publications that occurred between the years 2012–2013 have higher numbers of citations compared to the authors who collaborated with publications that occurred between the years 2014–2015. The number of citations contributes to the strength of the connection between the authors represented by the distance between the authors. Authors with higher numbers of citations have higher binding strength. This representation suggests that the articles published by the cluster in the period 2012–2013 have higher numbers of citations. (B) The authors who make up the cluster with the highest number of publications are represented by heat islands demonstrating the citation density (number of citations/year of publication). The size of the heat island corresponds to the citation density. Authors with high citation density are closer, suggesting that publications that occurred in collaboration between them have higher numbers of citations.
3.3. Global distribution of the 100 most cited articles
The list of the 100 most cited articles of WoS-CC has more articles from the Asian (55%) and North America (23%) continents. China is the country with the most articles and most citations on the list. In addition to China, countries like the USA, India and South Korea also have high numbers of articles on the list. The Asian continent has more countries with articles on the list compared to other continents. Africa and Central America are the only continent that does not have countries with articles on the list (Figure 4).
Figure 4. Worldwide distribution of the 100 most cited articles in PD and PC. Countries from the same continent are represented by the same color. The intensity of the color varies according to the presence or absence of publications with a high number of citations on PD and CP by country. Countries with stronger color intensity have publications with a high number of citations on PD and PC.
3.4. Distribution of the 100 most cited articles by journals, periods, and experimental design
Brain Research Journal has the highest number of articles in the list (5 articles). The journals Free Radical Biology and Medicine and Journal of Neuroscience Research presented four articles. The other journals that are part of the list have less than three articles (Table 3).
Table 3. Frequencies of characteristics of the 100 most-cited papers in PD and PC.
The most prolific periods in terms of publications on list of the 100 most cited articles of WoS-CC were 2012–2010 (26 publications), 2009–2007 (23 publications), and 2015–2013 (22 publications) respectively (Table 3). On the other hand, the period with most papers citations was 2015–2013 (3,681 citations), followed by 2009–2007 (2,479) and 2012–2010 (2,249).
The most used PD models were in vitro (47 papers), in vivo (32 papers) and in vitro + in vivo (14 papers) study designs, totaling the largest number of citations (5,124, 3,120, and 1,134 respectively; Table 3). Other study designs like bibliographic studies that did not have the type of review determined (5 papers), observational study (cross-sectional; 01 paper) and in vitro + in silico (01 paper) had a low occurrence on the top 100 list in the WoS-CC (Table 3).
3.5. Most evaluated compounds, subclasses and therapeutic targets among the 100 most cited articles
The compounds EGCG, quercetin, curcumin e baicalein are the most discussed (19, 15, 9, and 9 papers respectively) in the top 100 list in the WoS-CC, totaling the largest number of citations (2,394, 1,798, 1,183, and 1,060 respectively). The subclasses flavanol, flavones and flavonol are the most discussed (27, 22, and 21 papers respectively) in the top 100 list in the WoS-CC, totaling the largest number of citations (3,354, 2,434, and 2,444, respectively; Table 4).
Table 4. Number of articles published by phenolic compounds, subclasses and therapeutic target.
The most discussed targeted PD therapy on the WoS-CC Top 100 list was oxidative stress (68 articles), followed by neuroinflammation (20 articles), α-syn fibrils (15 articles) and mitochondrial dysfunction (8 articles; Table 4). However, evaluating the citation ratio it is evident that α-syn fibrils have the highest citation rate per article followed by oxidative stress, neuroinflammation and mitochondrial dysfunction (Table 4).
3.6. Keywords that occurred in the 100 most cited articles
Out of the top 100 most-cited publications, only 82 articles contained author keywords. The keywords that occurred in at least two articles were presented in Figure 5. The most frequently used keyword was parkinson’s disease (n = 54), followed by neuroprotection (n = 20), apoptosis (n = 11), rotenone (n = 11), 6-OHDA (n = 9), 11 alpha-synuclein (n = 8), polyphenols (n = 8). A total of 214 author keywords were identified.
Figure 5. Author keyword network analysis with 2 or more occurrences. The node size represents the frequency of the author keyword with larger nodes indicating greater frequency. The color of the node represents the possibility of co-occurrence of author keywords among the 100 most cited articles on PD and PC with nodes of the same color demonstrating that there is co-occurrence between author keywords in the same article. The thickness of the line between nodes represents the strength of linkage between author keywords with strong linkage strengths being demonstrated by thicker lines. More frequent author keywords have stronger linking strength.
4. Discussion
From the list of the 100 most cited articles on PD and PCs, the oldest article published in 2001, which also has the highest number of citations and the most recent article published in 2020, was identified. Asia and China were the continent and the country with the highest number of papers on the list. The period with the highest number of articles published was between 2012 and 2010 and the most common experimental design was laboratory studies, especially in vitro studies. The compounds EGCG, quercetin, curcumin andbaicalein were the most evaluated compounds and oxidative stress was the most therapeutic target among the papers.
The number of citations indicates the quality of an article according to the scientific community (Fardi et al., 2017). Articles with more than 100 citations are recognized as classics depending on the research area. Classic articles influence research and scientific practice (Arshad et al., 2020). In the list of the 100 most cited, 38 articles received more than 100 citations and can be called classics. The other articles received at least 49 citations.
Older articles tend to accumulate citations over time, then become references, as is the case of the most cited article (n citation = 434) in the list that was published in 2001. More recent articles, despite having lower numbers of citations, present new research possibilities within the area of interest (Feijoo et al., 2014). The most recent article on the list demonstrates that the mechanism involved in neuroprotection against PD may also occur due to the anti-inflammatory potential of PCs through the regulation of cytokines and neurotrophic factors (Brunetti et al., 2020).
Author Lee, S. M. Y. leads the cluster with the highest number of research (n = 20) in addition to having greater link strength (total link strength = 30), although he is not the author with the highest number of citations (n citation = 399). He is a professor and deputy director of the Institute of Chinese Medical Sciences at the University of Macau. He is interested in natural products that can be used as therapeutic agents in brain disorders. His dedication to education and research in the fields of molecular biochemistry biology, pharmacology pharmacy and neuroscience neurology.
PD is the second neurodegenerative disease with the highest incidence in the world. Its prevalence is higher in Anglo-Saxon America and Europe compared to Asia, Latin America and Africa (Benito-León and Louis, 2013). Despite the fact that the Asian continent has a low prevalence of the disease, it was the one that published the most articles on PD and PCs. The research on PD has increased 33-fold in the last 35 years in the Asian continent. This increase may be related to population aging and the new phase of economic development based on the production, communication and consumption of knowledge (Pajo et al., 2020).
China was the country with the most articles and the most citations in the list. In addition to China, countries such as the USA, India and South Korea also had high numbers of articles in the list. The high scientific production on PD and PCs may be related to traditional Chinese medicine (TCM), which has lower costs than Western medicine and more than 170 ingredients for the treatment of the disease, including PCs. The benefits and molecular mechanisms of TCM have been evaluated in preclinical studies, which may lead to the discovery of new therapeutic candidates for the treatment of PD (Li and Le, 2021).
In addition, China already stood out in scientific production on PD between 2013 and 2017, publishing 3,986 articles, behind only the USA. The high number of publications in this period was related to the standardization through guidelines (Chen et al., 2016) on the management of the disease in the country, efforts to reduce the economic burden related to the treatment of the disease and government incentives for publication in English newspapers (Robert et al., 2019).
The number of citations an article receives also contributes to the impact factor that determines the academic prestige of scientific journals. This factor in the year 2020 depended on the sum of the number of citations of early access articles with an early access year in 2020, early access articles with a final publication year in 2020 and an early access year in 2019 or earlier, and unanticipated access articles with a final publication year in 2020 divided by the sum of the number of articles published in the year of evaluation and in the year prior to the evaluation. Thus, journals that have articles with a high number of citations do not necessarily have a high impact factor, as is the case of the 3 three journals with the highest number of articles in the list.
The level of evidence of research is related to the experimental design. According to evidence-based practice systematic reviews and clinical studies are considered more important. As seen, in vitro laboratory studies are the most common experimental designs among the 100 articles. The development of these preliminary studies is necessary to carry out an initial screening regarding the effective concentration for bioactivity and toxicity (Ferreira et al., 2017). However, the concentrations evaluated in laboratory studies are not representative of the concentrations and chemical structure that reach the target organ (Perdigão et al., 2023).
After consumption, PCs can be hydrolyzed by intestinal enzymes, but most reach the colon, where they undergo hydrolysis and biotransformation reactions by microbiota enzymes and are then absorbed. Metabolites undergo conjugation reactions in the liver before entering the brain. The penetration of metabolites into the brain depends on the ability to bind to brain efflux transporters present in the blood–brain barrier and on lipophilicity. Metabolites reach the brain at concentrations less than 1 nmol/g of brain tissue (Pandareesh et al., 2015).
More than 10,000 PCs have been identified, of which approximately 500 are dietary compounds (Vuolo et al., 2018). The number of compounds that occurred among the 100 most cited articles (n = 51) is not representative of the amount of dietary phenolic compounds, however the compounds EGCG, quercetin, curcumin and baicalein were the most evaluated among the papers (19, 15, 9, and 9 papers, respectively), with the highest number of citations (2,394, 1,798, 1,183, and 1,060, respectively).
EGCG, the most evaluated compound in the list, can be found abundantly in green tea leaves, oolong tea, and black tea leaves (Eng et al., 2018). The estimated daily intake of EGCG through green tea consumption can reach approximately 560 mg/day for individuals consuming an average of 750 ml/day of green tea (Hu et al., 2018). Green tea is among the foods that are prescribed for the prevention of PD in TCM (Li and Le, 2021).
Quercetin, curcumin and baicalein compounds were widely evaluated among the papers as well. Quercetin is mostly conjugated to sugar moieties such as glucose or rutinose and can be found in high concentrations in Ginkgo Biloba, a TCM herb, onion, lettuce, chili pepper, cranberry, tomato, broccoli and apple, which contribute to an estimated dietary intake of 6–18 mg/day in the USA, China and the Netherlands (Ishisaka et al., 2011; Guo and Bruno, 2015).
The compound curcumin is extracted from turmeric and is widely used in Asian medicine to treat respiratory and liver diseases and inflammation. The pharmacological activities of curcumin include anti-inflammatory, antimicrobial, antioxidant, among others. Strategies such as nanoencapsulation, liposomes, micelles are being developed to increase bioavailability (Zhenqi et al., 2020).
Baicalein can be found in the root of Scutellaria baicalensis, an east Asian plant widely used in TCM to treat diseases (Arredondo et al., 2015). Baicalein has low water solubility for this reason, and it is poorly bioavailable, which makes its application in neuroprotectiv therapies difficult (Zhang et al., 2020). PCs, despite having common structural elements, have structural characteristics such as their degree of oxidation and substituents (position, number and nature of groups attached to rings A and B and the presence of glycosidic bonds) that affect their bioactive potential (Castillo et al., 2000). The subclasses flavanol, flavones, and flavonol were the most discussed (27, 22, and 21 papers, respectively) in the top 100 list in the WoS-CC, with the highest number of citations (3,547, 2,434, and 2,444, respectively; Table 4).
Flavanols, the most evaluated subclass among the 100 articles, present the ortho-dihydroxy (catecholic) group in the B ring, providing the delocalization of electrons, which contributes to a high antioxidant activity, which may be related to the number of studies that evaluated PCs and their effects on oxidative stress as a therapeutic target (Latos-Brozio and Masek, 2019).
The most discussed targeted PD therapy in the WoS-CC top 100 list was oxidative stress (68 articles). The interest in the mechanism used by PCs to reduce intracellular levels of ROS is recent, although the demonstration of the antioxidant potential of PCs in neurons is not (Reglodi et al., 2017). The search for answers makes this therapeutic target the most studied through laboratory models that are important tools, as they provide insights into behavioral improvements in parallel with the improvement in the oxidative state after exposure to PCs, for example, modulating the Nrf-2 signaling pathway and inducing increased expression of antioxidant enzymes such as SOD, CAT, and GSH (Table 2).
Other therapeutic targets for PCs in PD demonstrated in the 100 most cited articles were neuroinflammation (20 articles), α-syn fibrils (15 articles) and mitochondrial dysfunction (8 articles; Table 4). The neuroprotective effects of PCs include reduced expression of cytokines such as IL-6, TNF-α, IL-1b, and COX-2; the breakdown and inhibition of the formation of α-syn fibrils; and the upregulation of complex I activity in the mitochondria (Table 2).
Keywords are essential for discovering scientific articles. They are used as codes to access literature in a particular area. When using keywords in the search, you get more relevant results compared to using a phrase. Despite its importance, there are articles that do not bring keywords and make retrieval difficult during the search (Natarajan et al., 2010).
The most used keywords among the 100 articles include neuroprotection 6-OHDA antioxidant apoptosis. These words can help in the search for articles related to the topic in addition to indicating an overview of the research because they are words that represent therapeutic targets mechanisms of the neuroprotective effect and neurotoxins used in the papers.
5. Conclusion
The present study identified the 100 most cited articles on PD and PCs. The increased incidence of aging-related diseases due to the increase in the number of elderly people in the world has motivated countries such as China and the USA to seek other strategies for the treatment of PD in order to reduce the side effects and costs of available treatment. Plant foods and beverages have been used for a long time by TCM to treat neurodegenerative diseases, encouraging the search for the mechanisms behind the neuroprotective effect. Research mainly in laboratory models on the use of PCs against PD has grown since 2007 and has highlighted bioactive potentials that include antioxidant and anti-inflammatory activity. Despite the promising results obtained, clinical studies are needed to obtain more conclusive answers about the neuroprotective effects of PCs in humans, as the bioactive potential is influenced by bioavailability.
Author contributions
JP, BT, and DB-d-S performed experiments, analyzed and interpreted the data, and drafted the manuscript. PN, RL, and HR formulated the study concept, designed the study, and made critical revisions of the manuscript. All authors contributed to the article and approved the submitted version.
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.
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.
Supplementary material
The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnagi.2023.1149143/full#supplementary-material
References
An, L. J., Guan, S., Shi, G. F., Bao, Y. M., Duan, Y. L., and Jiang, B. (2006). Protocatechuic acid from Alpinia oxyphylla against MPP+-induced neurotoxicity in PC12 cells. Food Chem. Toxicol. 44, 436–443. doi: 10.1016/j.fct.2005.08.017
Anandhan, A., Tamilselvam, K., Radhiga, T., Rao, S., Essa, M. M., and Manivasagam, T. (2012). Theaflavin, a black tea polyphenol, protects nigral dopaminergic neurons against chronic MPTP/probenecid induced Parkinson’s disease. Brain Res. 1433, 104–113. doi: 10.1016/j.brainres.2011.11.021
Antunes, M. S., Goes, A. T. R., Boeira, S. P., Prigol, M., and Jesse, C. R. (2014). Protective effect of hesperidin in a model of Parkinson’s disease induced by 6-hydroxydopamine in aged mice. Nutrition 30, 1415–1422. doi: 10.1016/j.nut.2014.03.024
Anusha, C., Sumathi, T., and Joseph, L. D. (2017). Protective role of apigenin on rotenone induced rat model of Parkinson’s disease: suppression of neuroinflammation and oxidative stress mediated apoptosis. Chem. Biol. Interact. 269, 67–79. doi: 10.1016/j.cbi.2017.03.016
Aquilano, K., Baldelli, S., Rotilio, G., and Ciriolo, M. R. (2008). Role of nitric oxide synthases in Parkinson’s disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem. Res. 33, 2416–2426. doi: 10.1007/s11064-008-9697-6
Ardah, M. T., Paleologou, K. E., Lv, G., Khair, S. B. A., Al, K. A. K., Minhas, S. T., et al. (2014). Structure activity relationship of phenolic acid inhibitors of α-synuclein fibril formation and toxicity. Front. Aging Neurosci. 6:197. doi: 10.3389/fnagi.2014.00197
Arredondo, F., Echeverry, C., Blasina, F., Vaamonde, L., Díaz, M., Rivera, F., et al. (2015). “Flavones and Flavonols in brain and disease: facts and pitfalls” in Bioactive nutraceuticals and dietary supplements in neurological and brain disease: Prevention and therapy. eds. R. R. Watson and V. R. Preedy (Elsevier Inc.), 229–236.
Arshad, A. I., Ahmad, P., Karobari, M. I., Asif, J. A., Alam, M. K., Mahmood, Z., et al. (2020). Antibiotics: a bibliometric analysis of top 100 classics. Antibiotics 9:219. doi: 10.3390/antibiotics9050219
Ay, M., Luo, J., Langley, M., Jin, H., Anantharam, V., Kanthasamy, A., et al. (2017). Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and MitoPark transgenic mouse models of Parkinson’s disease. J. Neurochem. 141, 766–782. doi: 10.1111/jnc.14033
Bala, A., and Gupta, B. (2013). Parkinson′s disease in India: An analysis of publications output during 2002-2011. Int. J. Nutr. Pharmacol. Neurol. Dis. 3:254. doi: 10.4103/2231-0738.114849
Baldiotti, A. L. P., Amaral-Freitas, G., Barcelos, J. F., Freire-Maia, J., de França, P. M., Freire-Maia, F. B., et al. (2021). The top 100 most-cited papers in cariology: a bibliometric analysis. Caries Res. 55, 32–40. doi: 10.1159/000509862
Balestrino, R., and Schapira, A. H. V. (2020). Parkinson disease. Eur. J. Neurol. 27, 27–42. doi: 10.1111/ene.14108
Benito-León, J., and Louis, E. D. (2013). The top 100 cited articles in essential tremor. Tremor Other Hyperkinet. Mov. 3, 1–14. doi: 10.5334/tohm.128
Bergström, A. L., Kallunki, P., and Fog, K. (2016). Development of passive immunotherapies for Synucleinopathies. Mov. Disord. 31, 203–213. doi: 10.1002/mds.26481
Bournival, J., Plouffe, M., Renaud, J., Provencher, C., and Martinoli, M. G. (2012). Quercetin and sesamin protect dopaminergic cells from MPP+-induced neuroinflammation in a microglial (N9)-neuronal (PC12) coculture system. Oxidative Med. Cell. Longev. 2012:921941, 1–11. doi: 10.1155/2012/921941
Bournival, J., Quessy, P., and Martinoli, M. G. (2009). Protective effects of resveratrol and quercetin against MPP+ -nduced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons. Cell. Mol. Neurobiol. 29, 1169–1180. doi: 10.1007/s10571-009-9411-5
Brunetti, G., di Rosa, G., Scuto, M., Leri, M., Stefani, M., Schmitz-Linneweber, C., et al. (2020). Healthspan maintenance and prevention of parkinson’s-like phenotypes with hydroxytyrosol and oleuropein aglycone in C. elegans. Int. J. Mol. Sci. 21, 1–23. doi: 10.3390/ijms21072588
Bureau, G., Longpré, F., and Martinoli, M. G. (2008). Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J. Neurosci. Res. 86, 403–410. doi: 10.1002/jnr.21503
Cao, Q., Qin, L., Huang, F., Wang, X., Yang, L., Shi, H., et al. (2017). Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson’s disease model mice through PI3K/Akt and ERK signaling pathways. Toxicol. Appl. Pharmacol. 319, 80–90. doi: 10.1016/j.taap.2017.01.019
Caruana, M., Högen, T., Levin, J., Hillmer, A., Giese, A., and Vassallo, N. (2011). Inhibition and disaggregation of α-synuclein oligomers by natural polyphenolic compounds. FEBS Lett. 585, 1113–1120. doi: 10.1016/j.febslet.2011.03.046
Castillo, J., Benavente-García, O., Lorente, J., Alcaraz, M., Redondo, A., Ortuño, A., et al. (2000). Antioxidant activity and radioprotective effects against chromosomal damage induced in vivo by X-rays of flavan-3-ols (Procyanidins) from grape seeds (Vitis vinifera): comparative study versus other phenolic and organic compounds. J. Agric. Food Chem. 48, 1738–1745. doi: 10.1021/jf990665o
Chao, J., Yu, M. S., Ho, Y. S., Wang, M., and Chang, R. C. C. (2008). Dietary oxyresveratrol prevents parkinsonian mimetic 6-hydroxydopamine neurotoxicity. Free Radic. Biol. Med. 45, 1019–1026. doi: 10.1016/j.freeradbiomed.2008.07.002
Chaturvedi, R. K., Shukla, S., Seth, K., Chauhan, S., Sinha, C., Shukla, Y., et al. (2006). Neuroprotective and neurorescue effect of black tea extract in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. Neurobiol. Dis. 22, 421–434. doi: 10.1016/j.nbd.2005.12.008
Chen, S., Chan, P., Sun, S., Chen, H., Zhang, B., Le, W., et al. (2016). The recommendations of Chinese Parkinson’s disease and movement disorder society consensus on therapeutic management of Parkinson’s disease. Transl. Neurodegener. 5:12. doi: 10.1186/s40035-016-0059-z
Chen, H. Q., Jin, Z. Y., Wang, X. J., Xu, X. M., Deng, L., and Zhao, J. W. (2008). Luteolin protects dopaminergic neurons from inflammation-induced injury through inhibition of microglial activation. Neurosci. Lett. 448, 175–179. doi: 10.1016/j.neulet.2008.10.046
Chen, Y., Zhang, D. Q., Liao, Z., Wang, B., Gong, S., Wang, C., et al. (2015). Anti-oxidant polydatin (piceid) protects against substantia nigral motor degeneration in multiple rodent models of Parkinson’s disease. Mol. Neurodegener. 10, 1–14. doi: 10.1186/1750-1326-10-4
Cheng, Y., He, G., Mu, X., Zhang, T., Li, X., Hu, J., et al. (2008). Neuroprotective effect of baicalein against MPTP neurotoxicity: behavioral, biochemical and immunohistochemical profile. Neurosci. Lett. 441, 16–20. doi: 10.1016/j.neulet.2008.05.116
Cheynier, V., Comte, G., Davies, K. M., Lattanzio, V., and Martens, S. (2013). Plant phenolics: recent advances on their biosynthesis, genetics, andecophysiology. Plant Physiol. Biochem. 72, 1–20. doi: 10.1016/j.plaphy.2013.05.009
Chung, W. G., Miranda, C. L., and Maier, C. S. (2007). Epigallocatechin gallate (EGCG) potentiates the cytotoxicity of rotenone in neuroblastoma SH-SY5Y cells. Brain Res. 1176, 133–142. doi: 10.1016/j.brainres.2007.07.083
Cieslik, M., Pyszko, J., and Strosznajder, J. B. (2013). Docosahexaenoic acid and tetracyclines as promising neuroprotective compounds with poly(ADP-ribose) polymerase inhibitory activities for oxidative/genotoxic stress treatment. Neurochem. Int. 62, 626–636. doi: 10.1016/j.neuint.2013.02.016
Connolly, B. S., and Lang, A. E. (2014). Pharmacological treatment of Parkinson disease: a review. JAMA 311, 1670–1683. doi: 10.1001/jama.2014.3654
Cui, Q., Li, X., and Zhu, H. (2016). Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway. Mol. Med. Rep. 13, 1381–1388. doi: 10.3892/mmr.2015.4657
Datla, K. P., Christidou, M., Widmer, W. W., Rooprai, H. K., and Dexter, D. T. (2001). Tissue distribution and neuroprotective effects of citrus avonoid tangeretin in a rat model of Parkinson’s disease. Neuropharmacol. Neurotoxicol. Nneuro. 12, 959–4965. doi: 10.1097/00001756-200112040-00053
Datla, K. P., Zbarsky, V., Rai, D., Parkar, S., Osakabe, N., Aruoma, O. I., et al. (2007). Short-term supplementation with plant extracts rich in flavonoids protect nigrostriatal dopaminergic neurons in a rat model of Parkinson’s disease. J. Am. Coll. Nutr. 26, 341–349. doi: 10.1080/07315724.2007.10719621
Dorsey, E. R., Constantinescu, R., Thompson, J. P., Biglan, K. M., Holloway, R. G., Kieburtz, K., et al. (2007). Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 68, 384–386. doi: 10.1212/01.wnl.0000247740.47667.03
Du, X. X., Xu, H. M., Jiang, H., Song, N., Wang, J., and Xie, J. X. (2012). Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson’s disease. Neurosci. Bull. 28, 253–258. doi: 10.1007/s12264-012-1238-2
Eng, Q. Y., Thanikachalam, P. V., and Ramamurthy, S. (2018). Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases. J. Ethnopharmacol. 210, 296–310. doi: 10.1016/j.jep.2017.08.035
Etminan, M., Gill, S. S., and Samii, A. (2005). Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson’s disease: a meta-analysis. Lancet Neurol. 4, 362–365. doi: 10.1016/S1474-4422(05)70097-1
Fardi, A., Kodonas, K., Lillis, T., and Veis, A. (2017). Top-cited articles in implant dentistry. Int. J. Oral Maxillofac. Implants 32, 555–564. doi: 10.11607/jomi.5331
Feijoo, J. F., Limeres, J., Fernández-Varela, M., Ramos, I., and Diz, P. (2014). The 100 most cited articles in dentistry. Clin. Oral Investig. 18, 699–706. doi: 10.1007/s00784-013-1017-0
Ferreira, I. C. F. R., Martins, N., and Barros, L. (2017). Phenolic compounds and its bioavailability: in vitro bioactive compounds or health promoters? Adv. Food Nutr. Res. 82, 1–44. doi: 10.1016/bs.afnr.2016.12.004
Flint Beal, M., Oakes, D., Shoulson, I., Henchcliffe, C., Galpern, W. R., Haas, R., et al. (2014). A randomized clinical trial of high-dosage coenzyme Q10 in early parkinson disease no evidence of benefit. JAMA Neurol. 75, 543–552. doi: 10.1001/jamaneurol.2014.131
Gao, X., Cassidy, A., Schwarzschild, M. A., Rimm, E. B., and Ascherio, A. (2012). Habitual intake of dietary flavonoids and risk of Parkinson disease. Neurology 78, 1138–1145. doi: 10.1212/WNL.0b013e31824f7fc4
Goes, A. T. R., Jesse, C. R., Antunes, M. S., Lobo Ladd, F. V., AAB, L. L., Luchese, C., et al. (2018). Protective role of chrysin on 6-hydroxydopamine-induced neurodegeneration a mouse model of Parkinson’s disease: involvement of neuroinflammation and neurotrophins. Chem. Biol. Interact. 279, 111–120. doi: 10.1016/j.cbi.2017.10.019
Guan, S., Jiang, B., Bao, Y. M., and An, L. J. (2006). Protocatechuic acid suppresses MPP+-induced mitochondrial dysfunction and apoptotic cell death in PC12 cells. Food Chem. Toxicol. 44, 1659–1666. doi: 10.1016/j.fct.2006.05.004
Guo, S., Bezard, E., and Zhao, B. (2005). Protective effect of green tea polyphenols on the SH-SY5Y cells against 6-OHDA induced apoptosis through ROS-NO pathway. Free Radic. Biol. Med. 39, 682–695. doi: 10.1016/j.freeradbiomed.2005.04.022
Guo, Y., and Bruno, R. S. (2015). Endogenous and exogenous mediators of quercetin bioavailability. J. Nutr. Biochem. 26, 201–210. doi: 10.1016/j.jnutbio.2014.10.008
Guo, S., Yan, J., Yang, T., Yang, X., Bezard, E., and Zhao, B. (2007). Protective effects of green tea polyphenols in the 6-OHDA rat model of Parkinson’s disease through inhibition of ROS-NO pathway. Biol. Psychiatry 62, 1353–1362. doi: 10.1016/j.biopsych.2007.04.020
Gustavsson, A., Svensson, M., Jacobi, F., Allgulander, C., Alonso, J., Beghi, E., et al. (2011). Cost of disorders of the brain in Europe 2010. Eur. Neuropsychopharmacol. 21, 718–779. doi: 10.1016/j.euroneuro.2011.08.008
Haleagrahara, N., and Ponnusamy, K. (2010). Neuroprotective effect of Centella asiatica extract (CAE) on experimentally induced parkinsonism in aged Sprague-Dawley rats. J. Toxicol. Sci. 35, 41–47. doi: 10.2131/jts.35.41
Haleagrahara, N., Siew, C. J., Mitra, N. K., and Kumari, M. (2011). Neuroprotective effect of bioflavonoid quercetin in 6-hydroxydopamine-induced oxidative stress biomarkers in the rat striatum. Neurosci. Lett. 500, 139–143. doi: 10.1016/j.neulet.2011.06.021
Hong, D. P., Fink, A. L., and Uversky, V. N. (2008). Structural characteristics of α-synuclein oligomers stabilized by the flavonoid baicalein. J. Mol. Biol. 383, 214–223. doi: 10.1016/j.jmb.2008.08.039
Hou, R. R., Chen, J. Z., Chen, H., Kang, X. G., Li, M. G., and Wang, B. R. (2008). Neuroprotective effects of (−)-epigallocatechin-3-gallate (EGCG) on paraquat-induced apoptosis in PC12 cells. Cell Biol. Int. 32, 22–30. doi: 10.1016/j.cellbi.2007.08.007
Hu, J., Webster, D., Cao, J., and Shao, A. (2018). The safety of green tea and green tea extract consumption in adults - results of a systematic review. Regul. Toxicol. Pharmacol. 95, 412–433. doi: 10.1016/j.yrtph.2018.03.019
Hussain, G., Zhang, L., Rasul, A., Anwar, H., Sohail, M. U., Razzaq, A., et al. (2018). Role of plant-derived flavonoids and their mechanism in attenuation of Alzheimer’s and Parkinson’s diseases: an update of recent data. Molecules 23:814. doi: 10.3390/molecules23040814
Ishisaka, A., Ichikawa, S., Sakakibara, H., Piskula, M. K., Nakamura, T., Kato, Y., et al. (2011). Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats. Free Radic. Biol. Med. 51, 1329–1336. doi: 10.1016/j.freeradbiomed.2011.06.017
Jagatha, B., Mythri, R. B., Vali, S., and Bharath, M. M. S. (2008). Curcumin treatment alleviates the effects of glutathione depletion in vitro and in vivo: therapeutic implications for Parkinson’s disease explained via in silico studies. Free Radic. Biol. Med. 44, 907–917. doi: 10.1016/j.freeradbiomed.2007.11.011
Jiang, M., Porat-Shliom, Y., Pei, Z., Cheng, Y., Xiang, L., Sommers, K., et al. (2010). Baicalein reduces E46K α-synuclein aggregation in vitro and protects cells against E46K α-synuclein toxicity in cell models of familiar Parkinsonism. J. Neurochem. 114, 419–429. doi: 10.1111/j.1471-4159.2010.06752.x
Jimenez-Del-Rio, M., Guzman-Martinez, C., and Velez-Pardo, C. (2010). The effects of polyphenols on survival and locomotor activity in drosophila melanogaster exposed to iron and paraquat. Neurochem. Res. 35, 227–238. doi: 10.1007/s11064-009-0046-1
Johnson, S. J., Diener, M. D., Kaltenboeck, A., Birnbaum, H. G., and Siderowf, A. D. (2013). An economic model of Parkinson’s disease: implications for slowing progression in the United States. Mov. Disord. 28, 319–326. doi: 10.1002/mds.25328
Kang, K. S., Wen, Y., Yamabe, N., Fukui, M., Bishop, S. C., and Zhu, B. T. (2010). Dual beneficial effects of (−)-epigallocatechin-3-gallate on levodopa methylation and hippocampal neurodegeneration: in vitro and in vivo studies. PLoS One 5:e11951. doi: 10.1371/journal.pone.0011951
Karobari, M. I., Maqbool, M., Ahmad, P., Abdul, M. S. M., Marya, A., Venugopal, A., et al. (2021). Endodontic microbiology: a bibliometric analysis of the top 50 classics. Biomed. Res. Int. 2021, 1–12. doi: 10.1155/2021/6657167
Karuppagounder, S. S., Madathil, S. K., Pandey, M., Haobam, R., Rajamma, U., and Mohanakumar, K. P. (2013). Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson’s disease in rats. Neuroscience 236, 136–148. doi: 10.1016/j.neuroscience.2013.01.032
Kavitha, M., Nataraj, J., Essa, M. M., Memon, M. A., and Manivasagam, T. (2013). Mangiferin attenuates MPTP induced dopaminergic neurodegeneration and improves motor impairment, redox balance and Bcl-2/Bax expression in experimental Parkinson’s disease mice. Chem. Biol. Interact. 206, 239–247. doi: 10.1016/j.cbi.2013.09.016
Khan, M. M., Ahmad, A., Ishrat, T., Khan, M. B., Hoda, M. N., Khuwaja, G., et al. (2010). Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson’s disease. Brain Res. 1328, 139–151. doi: 10.1016/j.brainres.2010.02.031
Khan, M. M., Kempuraj, D., Thangavel, R., and Zaheer, A. (2013). Protection of MPTP-induced neuroinflammation and neurodegeneration by pycnogenol. Neurochem. Int. 62, 379–388. doi: 10.1016/j.neuint.2013.01.029
Kieburtz, K., Tilley, B. C., Elm, J. J., Babcock, D., Hauser, R., Ross, G. W., et al. (2015). Effect of creatine monohydrate on clinical progression in patients with parkinson disease: a randomized clinical trial. JAMA 313, 584–593. doi: 10.1001/jama.2015.120
Kim, H. G., Ju, M. S., Shim, J. S., Kim, M. C., Lee, S. H., Huh, Y., et al. (2010). Mulberry fruit protects dopaminergic neurons in toxin-induced Parkinson’s disease models. Br. J. Nutr. 104, 8–16. doi: 10.1017/S0007114510000218
Kim, S. S., Lim, J., Bang, Y., Gal, J., Lee, S. U., Cho, Y. C., et al. (2012). Licochalcone E activates Nrf2/antioxidant response element signaling pathway in both neuronal and microglial cells: therapeutic relevance to neurodegenerative disease. J. Nutr. Biochem. 23, 1314–1323. doi: 10.1016/j.jnutbio.2011.07.012
Kim, H. J., Song, J. Y., Park, H. J., Park, H. K., Yun, D. H., and Chung, J. H. (2009). Naringin protects against rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells. Korean J. Physiol. Pharmacol. 13, 281–285. doi: 10.4196/kjpp.2009.13.4.281
Kujawska, M., and Jodynis-Liebert, J. (2018). Polyphenols in Parkinson’s disease: a systematic review of in vivo studies. Nutrients 10, 1–34. doi: 10.3390/nu10050642
Latos-Brozio, M., and Masek, A. (2019). Structure-activity relationships analysis of monomeric and polymeric polyphenols (quercetin, Rutin and Catechin) obtained by various polymerization methods. Chemist. Biodiv. 16:e1900426. doi: 10.1002/cbdv.201900426
Lee, E., Park, H. R., Ji, S. T., Lee, Y., and Lee, J. (2014). Baicalein attenuates astroglial activation in the 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson’s disease model by downregulating the activations of nuclear factor-κB, ERK, and JNK. J. Neurosci. Res. 92, 130–139. doi: 10.1002/jnr.23307
Leem, E., Nam, J. H., Jeon, M. T., Shin, W. H., Won, S. Y., Park, S. J., et al. (2014). Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson’s disease. J. Nutr. Biochem. 25, 801–806. doi: 10.1016/j.jnutbio.2014.03.006
Levites, Y., Amit, T., Youdim, M. B. H., and Mandel, S. (2002a). Involvement of protein kinase C activation and cell survival/cell cycle genes in green tea polyphenol (−)-epigallocatechin 3-gallate neuroprotective action. J. Biol. Chem. 277, 30574–30580. doi: 10.1074/jbc.M202832200
Levites, Y., Weinreb, O., Maor, G., Youdim, M. B. H., and Mandel, S. (2001). Green tea polyphenol (−)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. J. Neurochem. 78, 1073–1082. doi: 10.1046/j.1471-4159.2001.00490.x
Levites, Y., Youdim, M. B., Maor, G., and Mandel, S. (2002b). Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-kappaB) activation and cell death by tea extracts in neuronal cultures. Biochem. Pharmacol. 63, 21–29. doi: 10.1016/S0006-2952(01)00813-9
Li, X. X., He, G. R., Mu, X., Xu, B., Tian, S., Yu, X., et al. (2012). Protective effects of baicalein against rotenone-induced neurotoxicity in PC12 cells and isolated rat brain mitochondria. Eur. J. Pharmacol. 674, 227–233. doi: 10.1016/j.ejphar.2011.09.181
Li, T., Ho, Y. S., and Li, C. Y. (2008). Bibliometric analysis on global Parkinson’s disease research trends during 1991-2006. Neurosci. Lett. 441, 248–252. doi: 10.1016/j.neulet.2008.06.044
Li, R., Huang, Y. G., Fang, D., and Le, W. D. (2004). (−)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. J. Neurosci. Res. 78, 723–731. doi: 10.1002/jnr.20315
Li, S., and Le, W. (2021). Parkinson’s disease in traditional Chinese medicine. Lancet Neurol. 20:262. doi: 10.1016/S1474-4422(19)30224-8
Liu, Y., Carver, J. A., Calabrese, A. N., and Pukala, T. L. (2014). Gallic acid interacts with α-synuclein to prevent the structural collapse necessary for its aggregation. Biochim. Biophys. Acta, Proteins Proteomics 1844, 1481–1485. doi: 10.1016/j.bbapap.2014.04.013
Liu, L. X., Chen, W. F., Xie, J. X., and Wong, M. S. (2008). Neuroprotective effects of genistein on dopaminergic neurons in the mice model of Parkinson’s disease. Neurosci. Res. 60, 156–161. doi: 10.1016/j.neures.2007.10.005
Long, J., Gao, H., Sun, L., Liu, J., and Zhao-Wilson, X. (2009). Grape extract protects mitochondria from oxidative damage and improves locomotor dysfunction and extends lifespan in a drosophila Parkinson’s disease model. Rejuvenation Res. 12, 321–331. doi: 10.1089/rej.2009.0877
Lorenzen, N., Nielsen, S. B., Yoshimura, Y., Vad, B. S., Andersen, C. B., Betzer, C., et al. (2014). How epigallocatechin gallate can inhibit α-synuclein oligomer toxicity in vitro. J. Biol. Chem. 289, 21299–21310. doi: 10.1074/jbc.M114.554667
Lou, H., Jing, X., Wei, X., Shi, H., Ren, D., and Zhang, X. (2014). Naringenin protects against 6-OHDA-induced neurotoxicity via activation of the Nrf2/ARE signaling pathway. Neuropharmacology 79, 380–388. doi: 10.1016/j.neuropharm.2013.11.026
Lu, K. T., Ko, M. C., Chen, B. Y., Huang, J. C., Hsieh, C. W., Lee, M. C., et al. (2008). Neuroprotective effects of resveratrol on MPTP-induced neuron loss mediated by free radical scavenging. J. Agric. Food Chem. 56, 6910–6913. doi: 10.1021/jf8007212
Macedo, D., Tavares, L., McDougall, G. J., Vicente Miranda, H., Stewart, D., Ferreira, R. B., et al. (2015). (Poly)phenols protect from α-synuclein toxicity by reducing oxidative stress and promoting autophagy. Hum. Mol. Genet. 24, 1717–1732. doi: 10.1093/hmg/ddu585
Magalingam, K. B., Radhakrishnan, A. K., and Haleagrahara, N. (2015). Protective mechanisms of flavonoids in Parkinson’s disease. Oxidative Med. Cell. Longev. 2015:314560, 1–14. doi: 10.1155/2015/314560
Marras, C., Beck, J. C., Bower, J. H., Roberts, E., Ritz, B., Ross, G. W., et al. (2018). Prevalence of Parkinson’s disease across North America. NPJ Parkinsons Dis. 4:21. doi: 10.1038/s41531-018-0058-0
Meng, X., Munishkina, L. A., Fink, A. L., and Uversky, V. N. (2009). Molecular mechanisms underlying the flavonoid-induced inhibition of α-synuclein fibrillation. Biochemistry 48, 8206–8224. doi: 10.1021/bi900506b
Meng, X., Munishkina, L. A., Fink, A. L., and Uversky, V. N. (2010). Effects of various flavonoids on the α-synuclein fibrillation process. Parkinsons Dis. 2010:650794, 1–16. doi: 10.4061/2010/650794
Mercer, L. D., Kelly, B. L., Horne, M. K., and Beart, P. M. (2005). Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures. Biochem. Pharmacol. 69, 339–345. doi: 10.1016/j.bcp.2004.09.018
Molina-Jiménez, M. F., Sánchez-Reus, M. I., Andres, D., Cascales, M., and Benedi, J. (2004). Neuroprotective effect of fraxetin and myricetin against rotenone-induced apoptosis in neuroblastoma cells. Brain Res. 1009, 9–16. doi: 10.1016/j.brainres.2004.02.065
Molina-Jimenez, M. F., Sanchez-Reus, M. I., and Benedi, J. (2003). Effect of fraxetin and myricetin on rotenone-induced cytotoxicity in SH-SY5Y cells: comparison with N-acetylcysteine. Eur. J. Pharmacol. 472, 81–87. doi: 10.1016/S0014-2999(03)01902-2
Mu, X., He, G., Cheng, Y., Li, X., Xu, B., and Du, G. (2009). Baicalein exerts neuroprotective effects in 6-hydroxydopamine-induced experimental parkinsonism in vivo and in vitro. Pharmacol. Biochem. Behav. 92, 642–648. doi: 10.1016/j.pbb.2009.03.008
Mythri, R. B., and Bharath, M. M. (2012). Curcumin: a potential neuroprotective agent in Parkinson’s disease. Curr. Pharm. Des. 18, 91–99. doi: 10.2174/138161212798918995
Natarajan, K., Stein, D., Jain, S., and Elhadad, N. (2010). An analysis of clinical queries in an electronic health record search utility. Int. J. Med. Inform. 79, 515–522. doi: 10.1016/j.ijmedinf.2010.03.004
Nie, G., Cao, Y., and Zhao, B. (2002a). Protective effects of green tea polyphenols and their major component, (−)-epigallocatechin-3-gallate (EGCG), on 6-hydroxydopamine-induced apoptosis in PC12 cells. Redox Rep. 7, 171–177. doi: 10.1179/135100002125000424
Nie, G., Jin, C., Cao, Y., Shen, S., and Zhao, B. (2002b). Distinct effects of tea catechins on 6-hydroxydopamine-induced apoptosis in PC12 cells. Arch. Biochem. Biophys. 397, 84–90. doi: 10.1006/abbi.2001.2636
Okawara, M., Katsuki, H., Kurimoto, E., Shibata, H., Kume, T., and Akaike, A. (2007). Resveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults. Biochem. Pharmacol. 73, 550–560. doi: 10.1016/j.bcp.2006.11.003
Pajo, A. T., Espiritu, A. I., and Jamora, R. D. G. (2020). Scientific impact of movement disorders research from Southeast Asia: a bibliometric analysis. Parkinsonism Relat. Disord. 81, 205–212. doi: 10.1016/j.parkreldis.2020.10.043
Pan, T., Fei, J., Zhou, X., Jankovic, J., and Le, W. (2003a). Effects of green tea polyphenols on dopamine uptake and on MPP+ −induced dopamine neuron injury. Life Sci. 72, 1073–1083. doi: 10.1016/S0024-3205(02)02347-0
Pan, T., Jankovic, J., and Le, W. (2003b). Potential therapeutic properties of green tea polyphenols in Parkinson’s disease. Drugs Aging 20, 711–721. doi: 10.2165/00002512-200320100-00001
Pandareesh, M. D., Mythri, R. B., and Srinivas Bharath, M. M. (2015). Bioavailability of dietary polyphenols: factors contributing to their clinical application in CNS diseases. Neurochem. Int. 89, 198–208. doi: 10.1016/j.neuint.2015.07.003
Pandey, N., Strider, J., Nolan, W. C., Yan, S. X., and Galvin, J. E. (2008). Curcumin inhibits aggregation of α-synuclein. Acta Neuropathol. 115, 479–489. doi: 10.1007/s00401-007-0332-4
Park, J. A., Kim, S., Lee, S. Y., Kim, C. S., Kim, D. K., Kim, S. J., et al. (2008). Bene¢cial effects of carnosic acid on dieldrin-induced dopaminergic neuronal cell death. Neuroreport 19, 1301–1304. doi: 10.1097/WNR.0b013e32830abc1f
Patil, S. P., Jain, P. D., Sancheti, J. S., Ghumatkar, P. J., Tambe, R., and Sathaye, S. (2014). Neuroprotective and neurotrophic effects of Apigenin and Luteolin in MPTP induced parkinsonism in mice. Neuropharmacology 86, 192–202. doi: 10.1016/j.neuropharm.2014.07.012
Perdigão, J. M., Teixeira, B. J. B., Carvalho-da-Silva, V., Prediger, R. D., Lima, R. R., and Rogez, H. (2009). A critical analysis on the concentrations of phenolic compounds tested using in vitro and in vivo Parkinson’s disease models. Critical Reviews in Food Science and Nutrition 63, 1–20.
Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., et al. (2017). Parkinson disease. Nat. Rev. Dis. Primers 3, 1–21. doi: 10.1038/nrdp.2017.13
Reglodi, D., Renaud, J., Tamas, A., Tizabi, Y., Socías, S. B., Del-Bel, E., et al. (2017). Novel tactics for neuroprotection in Parkinson’s disease: role of antibiotics, polyphenols and neuropeptides. Prog. Neurobiol. 155, 120–148. doi: 10.1016/j.pneurobio.2015.10.004
Ren, Z. X., Zhao, Y. F., Cao, T., and Zhen, X. C. (2016). Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson’s disease by suppressing glycogen synthase kinase-3 beta activity. Acta Pharmacol. Sin. 37, 1315–1324. doi: 10.1038/aps.2016.42
Robert, C., Wilson, C. S., Lipton, R. B., and Arreto, C. D. (2019). Parkinson’s disease: evolution of the scientific literature from 1983 to 2017 by countries and journals. Parkinsonism Relat. Disord. 61, 10–18. doi: 10.1016/j.parkreldis.2018.11.011
Roghani, M., Niknam, A., Jalali-Nadoushan, M. R., Kiasalari, Z., Khalili, M., and Baluchnejadmojarad, T. (2010). Oral pelargonidin exerts dose-dependent neuroprotection in 6-hydroxydopamine rat model of hemi-parkinsonism. Brain Res. Bull. 82, 279–283. doi: 10.1016/j.brainresbull.2010.06.004
Rothwell, J. A., Perez-Jimenez, J., Neveu, V., Medina-Remón, A., M’Hiri, N., García-Lobato, P., et al. (2013). Phenol-explorer 3.0: a major update of the phenol-explorer database to incorporate data on the effects of food processing on polyphenol content. Database 2013, 1–8. doi: 10.1093/database/bat070
Smith, K. M., Eyal, E., and Weintraub, D. (2015). Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability. JAMA Neurol. 72, 88–95. doi: 10.1001/jamaneurol.2014.2472
Sriraksa, N., Wattanathorn, J., Muchimapura, S., Tiamkao, S., Brown, K., and Chaisiwamongkol, K. (2012). Cognitive-enhancing effect of quercetin in a rat model of Parkinson’s disease induced by 6-hydroxydopamine. Evid. Based Complement. Alternat. Med. 2012:823206, 1–9. doi: 10.1155/2012/823206
Strathearn, K. E., Yousef, G. G., Grace, M. H., Roy, S. L., Tambe, M. A., Ferruzzi, M. G., et al. (2014). Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinson’s disease. Brain Res. 1555, 60–77. doi: 10.1016/j.brainres.2014.01.047
Subramaniam, S. R., and Ellis, E. M. (2013). Neuroprotective effects of umbelliferone and esculetin in a mouse model of Parkinson’s disease. J. Neurosci. Res. 91, 453–461. doi: 10.1002/jnr.23164
Tamilselvam, K., Braidy, N., Manivasagam, T., Essa, M. M., Prasad, N. R., Karthikeyan, S., et al. (2013). Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson’s disease. Oxidative Med. Cell. Longev. 2013:102741, 1–11. doi: 10.1155/2013/102741
Tapias, V., Cannon, J. R., and Greenamyre, J. T. (2014). Pomegranate juice exacerbates oxidative stress and nigrostriatal degeneration in Parkinson’s disease. Neurobiol. Aging 35, 1162–1176. doi: 10.1016/j.neurobiolaging.2013.10.077
van Eck, N. J., and Waltman, L. (2010). Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics 84, 523–538. doi: 10.1007/s11192-009-0146-3
Vauzour, D., Corona, G., and Spencer, J. P. E. (2010). Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity. Arch. Biochem. Biophys. 501, 106–111. doi: 10.1016/j.abb.2010.03.016
Vauzour, D., Ravaioli, G., Vafeiadou, K., Rodriguez-Mateos, A., Angeloni, C., and Spencer, J. P. E. (2008). Peroxynitrite induced formation of the neurotoxins 5-S-cysteinyl-dopamine and DHBT-1: implications for Parkinson’s disease and protection by polyphenols. Arch. Biochem. Biophys. 476, 145–151. doi: 10.1016/j.abb.2008.03.011
Vuolo, M. M., Lima, V. S., and Maróstica Junior, M. R. (2018). “Phenolic compounds: structure, classification, and antioxidant power” in Bioactive compounds: health benefits and potential applications. ed. M. R. S. Campos (Elsevier), 33–50.
Wang, X., Chen, S., Ma, G., Ye, M., and Lu, G. (2005). Genistein protects dopaminergic neurons by inhibiting microglial activation. Neuroreport 16, 267–270. doi: 10.1097/00001756-200502280-00013
Wruck, C. J., Claussen, M., Fuhrmann, G., Römer, L., Schulz, A., Pufe, T., et al. (2007). Luteolin protects rat PC12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keap1-Nrf2-ARE pathway. J. Neural Transm. Suppl. 72, 57–67. doi: 10.1007/978-3-211-73574-9_9
Wu, W. Y., Wu, Y. Y., Huang, H., He, C., Li, W. Z., Wang, H. L., et al. (2015). Biochanin a attenuates LPS-induced pro-inflammatory responses and inhibits the activation of the MAPK pathway in BV2 microglial cells. Int. J. Mol. Med. 35, 391–398. doi: 10.3892/ijmm.2014.2020
Xu, Q., Langley, M., Kanthasamy, A. G., and Reddy, M. B. (2017). Epigallocatechin Gallate has a neurorescue effect in a mouse model of Parkinson disease. J. Nutr. 147, 1926–1931. doi: 10.3945/jn.117.255034
Xu, Y., Zhang, Y., Quan, Z., Wong, W., Guo, J., Zhang, R., et al. (2016). Epigallocatechin gallate (EGCG) inhibits alpha-synuclein aggregation: a potential agent for Parkinson’s disease. Neurochem. Res. 41, 2788–2796. doi: 10.1007/s11064-016-1995-9
Yabuki, Y., Ohizumi, Y., Yokosuka, A., Mimaki, Y., and Fukunaga, K. (2014). Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced parkinson model mice. Neuroscience 259, 126–141. doi: 10.1016/j.neuroscience.2013.11.051
Yamabe, K., Liebert, R., Flores, N., and Pashos, C. (2018). Health-related quality-of-life, work productivity, and economic burden among patients with Parkinson’s disease in Japan. J. Med. Econ. 21, 1206–1212. doi: 10.1080/13696998.2018.1522638
Ye, Q., Ye, L., Xu, X., Huang, B., Zhang, X., Zhu, Y., et al. (2012). Epigallocatechin-3-gallate suppresses 1-methyl-4-phenyl-pyridine-induced oxidative stress in PC12 cells via the SIRT1/PGC-1α signaling pathway. BMC Complement. Altern. Med. 12, 1–7. doi: 10.1186/1472-6882-12-82
Yu, S., Zheng, W., Xin, N., Chi, Z. H., Wang, N. Q., Nie, Y. X., et al. (2010). Curcumin prevents dopaminergic neuronal death through inhibition of the c-Jun N-terminal kinase pathway. Rejuvenation Res. 13, 55–64. doi: 10.1089/rej.2009.0908
Zbarsky, V., Datla, K. P., Parkar, S., Rai, D. K., Aruoma, O. I., and Dexter, D. T. (2005). Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson’s disease. Free Radic. Res. 39, 1119–1125. doi: 10.1080/10715760500233113
Zhang, Z. T., Cao, X. B., Xiong, N., Wang, H. C., Huang, J. S., Sun, S. G., et al. (2010). Morin exerts neuroprotective actions in Parkinson disease models in vitro and in vivo. Acta Pharmacol. Sin. 31, 900–906. doi: 10.1038/aps.2010.77
Zhang, Z. J., Cheang, L. C. V., Wang, M. W., and Lee, S. M. Y. (2011). Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish. Int. J. Mol. Med. 27, 195–203. doi: 10.3892/ijmm.2010.571
Zhang, Z. J., Cheang, L. C. V., Wang, M. W., Li, G. H., Chu, I. K., Lin, Z. X., et al. (2012). Ethanolic extract of fructus alpinia oxyphylla protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish. Cell. Mol. Neurobiol. 32, 27–40. doi: 10.1007/s10571-011-9731-0
Zhang, Z., Cui, W., Li, G., Yuan, S., Xu, D., Hoi, M. P. M., et al. (2012). Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways. J. Agric. Food Chem. 60, 8171–8182. doi: 10.1021/jf301511m
Zhang, Z., Li, G., Szeto, S. S. W., Chong, C. M., Quan, Q., Huang, C., et al. (2015). Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease. Free Radic. Biol. Med. 84, 331–343. doi: 10.1016/j.freeradbiomed.2015.02.030
Zhang, F., Shi, J. S., Zhou, H., Wilson, B., Hong, J. S., and Gao, H. M. (2010). Resveratrol protects dopamine neurons against lipopolysaccharide-induced neurotoxicity through its anti-inflammatory actions. Mol. Pharmacol. 78, 466–477. doi: 10.1124/mol.110.064535
Zhang, L., Yang, S., Huang, L., and Ho, P. C. L. (2020). Poly (ethylene glycol)-block-poly (D, L-lactide) (PEG-PLA) micelles for brain delivery of baicalein through nasal route for potential treatment of neurodegenerative diseases due to oxidative stress and inflammation: an in vitro and in vivo study. Int. J. Pharm. 591:119981. doi: 10.1016/j.ijpharm.2020.119981
Zhenqi, L., John, D. S., and Ananth, S. P. (2020). Recent developments in formulation design for improving oral bioavailability of curcumin: a review. J. Drug Deliv. Sci. Technol. 60:102082. doi: 10.1016/j.jddst.2020.102082
Zhu, M., Han, S., and Fink, A. L. (2013). Oxidized quercetin inhibits α-synuclein fibrillization. Biochim. Biophys. Acta Gen. Subj. 1830, 2872–2881. doi: 10.1016/j.bbagen.2012.12.027
Zhu, M., Rajamani, S., Kaylor, J., Han, S., Zhou, F., and Fink, A. L. (2004). The flavonoid baicalein inhibits fibrillation of α-synuclein and disaggregates existing fibrils. J. Biol. Chem. 279, 26846–26857. doi: 10.1074/jbc.M403129200
Glossary
Keywords: bibliometric, Parkinson’s disease, phenolic compound, bibliometric and network analysis, neuroprotection
Citation: Perdigão JM, Teixeira BJB, Baia-da-Silva DC, Nascimento PC, Lima RR and Rogez H (2023) Analysis of phenolic compounds in Parkinson’s disease: a bibliometric assessment of the 100 most cited papers. Front. Aging Neurosci. 15:1149143. doi: 10.3389/fnagi.2023.1149143
Edited by:
Michael J. Hurley, University College London, United KingdomReviewed by:
Janakiraman Udaiyappan, Virginia Commonwealth University, United StatesIrmgard Blanca Paris, Santo Tomas University, Chile
Copyright © 2023 Perdigão, Teixeira, Baia-da-Silva, Nascimento, Lima and Rogez. 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.
*Correspondence: Herve Rogez, frutas@ufpa.br