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molecules
Article
Curcumin: Total-Scale Analysis of the
Scientific Literature
Andy Wai Kan Yeung 1,* , Michal Horba´nczuk 2, Nikolay T. Tzvetkov 3,4 , Andrei Mocan 5,6,
Simone Carradori 7, Filippo Maggi 8, Joanna Marchewka 9, Stefania Sut 10,
Stefano Dall’Acqua 11 , Ren-You Gan 12 , Lyubka P. Tancheva 13, Timea Polgar 14,
Ioana Berindan-Neagoe 15,16,17 , Vasil Pirgozliev 18, Karel Šmejkal 19 and
Atanas G. Atanasov 9,14,20,*
1
Oral and Maxillofacial Radiology, Applied Oral Sciences, Faculty of Dentistry, The University of Hong Kong,
Hong Kong, China
2Warsaw University of Life Sciences, Faculty of Applied Informatics and Mathematics, 02-787 Warsaw,
Poland; mifune6@gmail.com
3Institute of Molecular Biology “Roumen Tsanev”, Department of Biochemical Pharmacology and Drug
Design, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, 1113 Sofia, Bulgaria;
ntzvetkov@gmx.de
4Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany
5Department of Pharmaceutical Botany, “Iuliu Ha¸tieganu” University of Medicine and Pharmacy, 23 Ghe.
Marinescu Street, 400337 Cluj-Napoca, Romania; mocan.andrei@umfcluj.ro
6
Laboratory of Chromatography, Institute of Advanced Horticulture Research of Transylvania, University of
Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
7Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini 31,66100 Chieti,
Italy; simone.carradori@unich.it
8School of Pharmacy, University of Camerino, 62032 Camerino, Italy; filippo.maggi@unicam.it
9
The Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrz˛ebiec, 05-552 Magdalenka,
Poland; J.Marchewka@ighz.pl
10 Department of Agronomy, Food, Natural Resources, Animals and Environment (DAFNAE), Agripolis
Campus, University of Padova, 35020 Padova, Italy; stefania_sut@hotmail.it
11 Department of Pharmaceutical and Pharmacological Sciences University of Padova, 35020 Padova, Italy;
stefano.dallacqua@unipd.it
12 Department of Food Science & Technology, School of Agriculture and Biology, Shanghai Jiao Tong
University, Shanghai 200240, China; renyougan@sjtu.edu.cn
13 Department of Behavioral Neurobiology, Institute of Neurobiology, Bulgarian Academy of Sciences,
1000 Sofia, Bulgaria; lyubkatancheva@gmail.com
14
GLOBE Program Association (GLOBE-PA), Grandville, MI, USA; timea.polgar@envisionbiotechnology.com
15 MEDFUTURE - Research Center for Advanced Medicine, 400037 Cluj-Napoca, Romania;
ioananeagoe29@gmail.com
16 Research Center for Functional Genomics, Biomedicine and Translational Medicine, Institute of Doctoral
Studies, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400037 Cluj-Napoca, Romania
17 Department of Experimental Pathology, “Prof. Dr. Ion Chiricuta”, The Oncology Institute, 400037
Cluj-Napoca, Romania
18 The National Institute of Poultry Husbandry, Harper Adams University, Shropshire TF10 8NB, UK;
vpirgozliev@harper-adams.ac.uk
19 Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences
Brno, Palackého tˇr. 1946/1, 612 42 Brno, Czech Republic; karel.mejkal@post.cz
20 Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria
*Correspondence: ndyeung@hku.hk (A.W.K.Y.); atanas.atanasov@univie.ac.at (A.G.A.); Tel.: +852-28590403
(A.W.K.Y.); +43-1-4277-55231 (A.G.A.)
Received: 1 March 2019; Accepted: 7 April 2019; Published: 9 April 2019
Abstract:
The current study aimed to provide a comprehensive bibliometric overview of the literature
on curcumin, complementing the previous reviews and meta-analyses on its potential health benefits.
Molecules 2019,24, 1393; doi:10.3390/molecules24071393 www.mdpi.com/journal/molecules
Molecules 2019,24, 1393 2 of 14
Bibliometric data for the current analysis were extracted from the Web of Science Core Collection
database, using the search string TOPIC=(“curcumin*”), and analyzed by the VOSviewer software.
The search yielded 18,036 manuscripts. The ratio of original articles to reviews was 10.4:1. More than
half of the papers have been published since 2014. The major contributing countries were the
United States, China, India, Japan, and South Korea. These publications were mainly published
in journals representing the following scientific disciplines: biochemistry, chemistry, oncology, and
pharmacology. There was a significant positive correlation between the total publication count
and averaged citations per manuscript for affiliations, but not for countries/regions and journals.
Chemicals that were frequently mentioned in the keywords of evaluated curcumin publications
included curcuminoids, resveratrol, chitosan, flavonoids, quercetin, and polyphenols. The literature
mainly focused on curcumin’s effects against cancer, inflammation, and oxidative stress. Cancer types
most frequently investigated were breast, colon, colorectal, pancreatic, and prostate cancers.
Keywords:
curcumin; pharmacology; bibliometrics; biochemistry; cancer; citation analysis;
VOSviewer; Web of Science
1. Introduction
Turmeric (Curcuma longa L., Zingiberaceae) is traditionally used in Indian medicine for the
treatment of various illnesses, mainly connected with inflammatory processes. According to the Plant
List database (http://www.theplantlist.org), the Curcuma genus includes more than 93 species, with
different use and content of active substances. Turmeric is cultivated mainly in India, China, Indonesia,
Jamaica, and Peru. The medicinal applications of turmeric have been known for thousands of years,
especially by Ayurvedic therapy, which uses turmeric for stomach disorders, as a tonic, for blood
cleansing, as well as for prevention or treatment of skin diseases. In addition, an administration of
turmeric is recommended in disorders of bile production, anorexia, rhinitis, sinusitis, cough, diabetic
lesions, disorders of liver functions, and rheumatism. The contemporary focus on turmeric and its
substances can be tracked back to the 1970s, when mechanisms of its anti-inflammatory, antibacterial,
and antioxidant properties started to be evaluated. However, readers should note that most of
the scientific papers reporting the biological effects of curcumin represent preliminary
in vitro
data,
obtained with biochemical (cell-free) assays or on cell culture models.
The aroma of turmeric is based on a bunch of sesquiterpenes. Typical examples are
(S)-ar-turmerone, zingiberene,
β
-turmerone, and curlone. Their ratio and the presence of a wide
range of other volatile compounds (e.g., monoterpenes) in various turmeric cultivars affect the aroma
of curcuma when used as a food seasoning [
1
]. The marker substances isolated from turmeric are
called curcuminoids. The main representative of this group of compounds is the bis-
α
,
β
-unsaturated
diketone curcumin (diferuloylmethane). Its structure had already been described by 1910. Curcumin
is a compound showing keto-enol tautomerism, with the predominance of the keto form in acidic
environment and stable enol form under basic conditions. Turmeric contains 2–5% of curcumin,
according to the origin. After extraction, it is characterized as a yellow crystalline powder, practically
insoluble in water, showing good solubility in fats and ethanol [2].
Curcumin is famous for its potential applications in the prevention and treatment of cancer [
3
],
as well as for its anti-inflammatory, antioxidant [
4
], and antiangiogenic activities [
5
]. These activities
were potentiated by the design and synthesis of structurally related analogues following a “lead
optimization” approach. Meanwhile, curcumin may also inhibit
β
-amyloid formation and hence be
potentially useful for preventing and treating Alzheimer’s disease [
6
–
10
]. There are several highly
cited reviews that summarize the above-mentioned important research findings about the health
beneficial effects of curcumin [
11
,
12
]. Meanwhile, similar to those in other research fields, such as
in nutritional neurosciences [
13
–
16
], there have already been many meta-analyses of the effects of
Molecules 2019,24, 1393 3 of 14
curcumin, including those with focus on downregulation of human tumor necrosis factor (TNF)-alpha
levels [
17
], alleviation of joint arthritis [
18
], and regulation of blood lipid levels [
19
]. With so many
publications available in the existing literature, a bibliometric analysis could identify and quantitatively
analyze the major themes of the curcumin research literature, as well as summarize the citation
performance of various contributors and topics. Similar analyses have already been published in
other research fields such as ethnopharmacology [
20
], food sciences [
21
], neuropharmacology [
22
],
nutraceuticals [23], and oncology [24].
The current study aimed to identify and analyze publications on curcumin to outline the major
contributors in terms of author affiliations, countries/regions, and journals. It also aimed to reveal
the major research themes present in the literature about curcumin, based on the publication and
citation data. These pieces of information should be helpful for readers, including audience without
deep previous knowledge of the topic, to quickly have a general overview of the curcumin literature
landscape, including prominent authors, major output countries, and prevailing major research topics
and trends. The provided information can also be used to identify potentially promising research
directions and possible collaboration partners, and to give initial orientation to direct further more
in-depth searches for the identification of relevant publications or research opportunities.
2. Materials and Methods
In November 2018, we accessed the Clarivate Analytics-owned Web of Science (WoS) Core
Collection online database to identify curcumin publications with the following search string:
TOPIC=(“curcumin*”). This search string identified publications that mentioned the word “curcumin”
or its derivatives in the title, abstract, or keywords. We did not place additional restriction on the
search strategy, such as publication year, publication type, or language. To gain insides into research
focused on extracts of the plant Curcuma longa/turmeric, an additional analysis was performed to
evaluate the publications that mentioned Curcuma longa or turmeric without mentioning curcumin,
using the search strategy: TOPIC=(“curcum*” OR “tumeric*” OR “turmeric*” NOT “curcumin*”).
Data Extraction
The publications identified from the search were evaluated by: (1) publication year; (2) author
affiliations; (3) countries/regions of the affiliations; (4) journal title; (5) WoS category; (6) publication
type; (7) language; and (8) total citation count. The full records and cited references of these publications
were downloaded and loaded into VOSviewer for further bibliometric analyses.
The VOSviewer software (v.1.6.8, 2018) is capable of extracting and analyzing the semantic
contents of the titles, abstracts, and keywords of publications, relating them to the citation count
data and generating a bubble map to visualize the results [
25
]. Default parameters were used for the
analyses and creation of bubble maps. The font size of the words in the bubble map indicates their
frequency of occurrence (multiple appearances in a single publication count as one). Two words are
nearer to each other if they co-occurred in the evaluated publications more frequently. Only words that
appeared in at least 1.0% (n= 181) of the manuscripts were analyzed and visualized. For the keyword
map, full counting method was used, meaning that each co-occurrence link carried the same weight.
The default “association strength method” was used for normalization of the co-occurrence matrix
with default values of attraction and repulsion.
We tested the possible correlation between total publication count and averaged citations per
manuscript for the affiliations, countries/regions, and journals. For these data, we only considered
entities that contributed to at least 0.01% (n= 19) of the publications. Pearson’s correlation test
was performed in SPSS 25.0 (IBM, New York, NY, USA). Test results with p< 0.05 were considered
statistically significant.
Molecules 2019,24, 1393 4 of 14
3. Results
The primary literature search resulted in 18,036 publications. The earliest articles on curcumin
indexed in WoS were published in 1970 and 1971, and they investigated the hypocholesterolemic
effect of curcumin in rats [
26
,
27
]. More than half of the analyzed papers have been published since
the year 2014. The large number of publications since 2014 could be attributed to the increased
publication productivity of China (publications since 2014 = 2443; 68.9% of total contributions) and
India (publications since 2014 = 1620; 51.8% of total contributions). The numbers of original articles
(n= 14,315) and reviews (n= 1378) were in the ratio of 10.4:1. The majority of the publications were
written in English (n= 17,871, 99.1%). Contributions came from 7729 organizations (author affiliations)
located in 125 countries/territories and were published in 2905 journals. The top five WoS categories
of the manuscripts were pharmacology and pharmacy (n= 3590, 19.9%), biochemistry and molecular
biology (n= 2526, 14.0%), oncology (n= 1,894, 10.5%), multidisciplinary chemistry (n= 1485, 8.2%), and
medicinal chemistry (n= 1469, 8.1%). The top five contributors with regard to journal, organization,
and country/territory are listed in Table 1. The five most productive countries were from Asia, except
the United States.
Table 1.
The top five contributor journals, organizations, and countries/territories of the
18,036 manuscripts.
Contributor Publication Count
(% of Total)
Citation Per
Manuscript
Journal
PLOS One 234 (1.3%) 21.6
FASEB Journal 197 (1.1%) 4.3
Cancer Research 191 (1.1%) 39.0
RSC Advances 191 (1.1%) 7.6
Journal of Agricultural and Food Chemistry 187 (1.0%) 41.2
Organization
Council of Scientific Industrial Research (CSIR India) 503 (2.8%) 12.1
University of Texas 307 (1.7%) 173.5
University of California 239 (1.3%) 71.1
Wenzhou Medical University 216 (1.2%) 9.6
Indian Institute of Technology 200 (1.1%) 20.2
Country/Territory
United States 4073 (22.3%) 39.0
China 3546 (19.7%) 15.3
India 3128 (17.3%) 23.4
Japan 990 (5.5%) 28.7
South Korea 884 (4.9%) 24.3
Pearson’s correlation tests revealed that there was a significant positive correlation between total publication count
and averaged citations per manuscript for affiliations (r = 0.147, p= 0.005), but not for countries/regions (r = 0.131,
p= 0.333
), or journals (r = 0.032, p= 0.656). These results implied that the citation advantage by publishing more
only existed in the affiliation level.
There were 422 terms that appeared in at least 1.0% (n= 181) of the evaluated publications.
By analyzing these words in the titles and abstracts of the 18,036 publications, we found that
some notable highly cited themes of the publications were related to the effects of curcumin and
its derivatives against cancer (n= 2583, citations per publication = 37.8), inflammation (n= 1210,
citations per publication = 38.8), and oxidative stress (n= 1266, citations per publication = 29.6)
(Figure 1). The top 20 recurring terms are listed in Table 2.
Molecules 2019,24, 1393 5 of 14
Molecules 2019, 24, x FOR PEER REVIEW 5 of 15
Figure 1. Bubble map visualizing words from titles and abstracts of the 18,036 curcumin
publications. We used VOSviewer software to analyze and visualize recurring terms from titles and
abstracts. Only words that appeared in at least 1.0% (n = 181) of the publications were analyzed and
visualized. There were 422 terms that appeared in at least 1.0% of the evaluated publications. The
word size indicates the appearance frequency of the words (multiple appearances in a single
manuscript count as one). Two words are closer to each other if they co-occurred more frequently in
the evaluated publications. Bubble colors represent the averaged citations of the terms.
Table 2. The top 20 recurring terms from titles and abstracts.
Term Occurrence (% of 18,036 publications)
Curcumin 13,722 (76.1%)
Effect 7958 (44.1%)
Study 7418 (41.1%)
Cell 6096 (33.8%)
Activity 5832 (32.3%)
Treatment 4917 (27.3%)
Compound 3661 (20.3%)
Level 3612 (20.0%)
Expression 3363 (18.6%)
Agent 3287 (18.2%)
Mechanism 3087 (17.1%)
Property 2939 (16.3%)
Concentration 2858 (15.8%)
Analysis 2735 (15.2%)
Inhibition 2720 (15.1%)
Pathway 2712 (15.0%)
Drug 2663 (14.8%)
Disease 2661 (14.8%)
Group 2606 (14.4%)
Protein 2597 (14.4%)
Figure 1.
Bubble map visualizing words from titles and abstracts of the 18,036 curcumin publications.
We used VOSviewer software to analyze and visualize recurring terms from titles and abstracts.
Only words that appeared in at least 1.0% (n= 181) of the publications were analyzed and visualized.
There were 422 terms that appeared in at least 1.0% of the evaluated publications. The word size
indicates the appearance frequency of the words (multiple appearances in a single manuscript count
as one). Two words are closer to each other if they co-occurred more frequently in the evaluated
publications. Bubble colors represent the averaged citations of the terms.
Table 2. The top 20 recurring terms from titles and abstracts.
Term Occurrence (% of 18,036 Publications)
Curcumin 13,722 (76.1%)
Effect 7958 (44.1%)
Study 7418 (41.1%)
Cell 6096 (33.8%)
Activity 5832 (32.3%)
Treatment 4917 (27.3%)
Compound 3661 (20.3%)
Level 3612 (20.0%)
Expression 3363 (18.6%)
Agent 3287 (18.2%)
Mechanism 3087 (17.1%)
Property 2939 (16.3%)
Concentration
2858 (15.8%)
Analysis 2735 (15.2%)
Inhibition 2720 (15.1%)
Pathway 2712 (15.0%)
Drug 2663 (14.8%)
Disease 2661 (14.8%)
Group 2606 (14.4%)
Protein 2597 (14.4%)
Moreover, we examined the data to identify the prevalence of the use of metabolomics, proteomics,
genomics, and transcriptomics, as well as clinical trials in curcumin research. “Metabolomic(s)” was
Molecules 2019,24, 1393 6 of 14
mentioned in 42 publications, with a total of 293 citations. For example, it was found that, via nuclear
magnetic resonance (NMR) spectroscopy-based metabolomics, in breast cancer cells the major target
of curcumin was metabolism of glutathione [
28
]. At the same time, “proteomic(s)” was mentioned in
62 publications, with a total of 526 citations. An example is a study showing that curcumin could bind
to 197 proteins in HCT116 colon cancer cell line, which results in downregulation of cellular protein
synthesis and induction of autophagy [
29
]. Meanwhile, “genomic(s)” was mentioned in 77 publications,
with a total of 1,691 citations. A representative study revealed that 1
α
,25-dihydroxyvitamin D(3)
and curcuminoids had additive effects in stimulating amyloid clearance in patients of Alzheimer’s
disease [
30
]. Similarly, the term “transcriptomic(s)” was mentioned in 20 publications, with a total
of 244 citations. For instance, it was found that curcumin-treated lipopolysaccharide (LPS)-primed
microglia showed limited neurotoxicity with the decrease of apoptosis [
31
]. In terms of original articles
with the term “clinical trial*”, there were 691 publications, with a total of 27,922 citations. Exemplars
included Phase I clinical trial of oral curcumin (C3 complex) intake in patients with advanced colorectal
cancer refractory to standard chemotherapies [
32
]; and Phase II trial of oral curcumin intake in patients
with advanced pancreatic cancer [33].
Subsequently, we analyzed the keywords included into publications by authors and WoS
(KeyWords Plus). As keywords are important for document searching and retrieval, authors usually
carefully consider keyword selection for relevance, and a higher frequency of keywords use could
indicate their importance. There were 108 keywords that appeared in at least 1.0% (n= 181) of the
evaluated publications (Figure 2). In the bubble map presented as Figure 2, the size of the text/bubble
is reflecting the frequency with which the keywords were used, and the color of the bubble is reflecting
the citation frequency of the manuscripts in which the keywords were occurring. Therefore, a bigger
size of the text/bubble might indicate a higher number of papers dealing with the respective topic, and
a higher “intensity” of the color (according to the presented “color scale”) reflects higher impact (more
citations obtained) of the manuscripts. The major themes were similar as reported above (Figure 1)
for the words in the titles and abstracts of the 18,036 publications. Here, as evident from Figure 2,
we observed that several cancers were frequently mentioned, such as breast (n= 417, citations per
publication = 26.4), colon (n= 208, citations per publication = 44.9), colorectal (n= 271, citations per
publication = 40.1), pancreatic (n= 207, citations per publication = 33.2), and prostate (n= 276, citations
per publication = 37.5) cancers. Frequently mentioned components for the potential mechanisms
included nuclear factor kappa-light-chain-enhancer of activated B cells (NF-
κ
B, n= 1558, citations per
publication = 48.4), nitric oxide synthase (NOS, n= 275, citations per publication = 73.9), and TNF-
α
(n= 203, citations per publication = 38.7). Curcumin may inhibit tumor growth by inhibiting NF-
κ
B
activation [
34
], and NOS [
35
]. Meanwhile, Alzheimer’s disease was also frequently mentioned (n= 746,
citations per publication = 30.5). The top 20 recurring keywords are listed in Table 3. The keywords
suggested that many of the studies were
in vitro
or
in vivo
using (cancer) cells, rats, and mice, but not
clinical studies in humans.
To analyze the temporal changes in the use of keywords, we separated and assessed publications
in four periods: 1989 and before, 1990s, 2000s, and 2010s. Unexpectedly, WoS did not record any
keywords for the papers published in 1989 and before. The top 20 recurring keywords for each of the
remaining three periods are listed in Table 4. It could be observed that antioxidant effects and cancer
remained popular throughout the three periods. Drug delivery, bioavailability, and nanoparticles were
emerging keywords that became popular since the 2010s, implying that more attention has been given
to improve the delivery of curcumin to target sites.
Molecules 2019,24, 1393 7 of 14
Molecules 2019, 24, x FOR PEER REVIEW 7 of 15
Figure 2. Bubble map visualizing keywords of the 18,036 curcumin publications. We used
VOSviewer software to analyze and visualize recurring keywords added to the publications by the
authors and by Web of Science. Only keywords that appeared in at least 1.0% (n = 181) of the
publications were analyzed and visualized. There were 108 keywords that appeared in at least 1.0%
of the evaluated publications. The word size indicates the appearance frequency of the words
(multiple appearances in a single manuscript count as one). Two words are closer to each other if
they co-occurred more frequently in the evaluated publications. Bubble colors represent the
averaged citations of the terms.
Table 3. The top 20 recurring keywords.
Keyword Occurrence (% of 18,036 Publications)
Curcumin 9,539 (52.9%)
Apoptosis 2,223 (12.3%)
In vitro 1,909 (10.6%)
Oxidative stress 1,834 (10.2%)
Nf kappa b 1,558 (8.6%)
Expression 1,543 (8.6%)
Cells 1,480 (8.2%)
Cancer 1,290 (7.2%)
Inhibition 1,269 (7.0%)
Activation 1,230 (6.8%)
Antioxidant 1,108 (6.1%)
Nanoparticles 1,021 (5.7%)
Drug delivery 939 (5.2%)
In vivo 880 (4.9%)
Inflammation 808 (4.5%)
Figure 2.
Bubble map visualizing keywords of the 18,036 curcumin publications. We used VOSviewer
software to analyze and visualize recurring keywords added to the publications by the authors and
by Web of Science. Only keywords that appeared in at least 1.0% (n= 181) of the publications were
analyzed and visualized. There were 108 keywords that appeared in at least 1.0% of the evaluated
publications. The word size indicates the appearance frequency of the words (multiple appearances
in a single manuscript count as one). Two words are closer to each other if they co-occurred more
frequently in the evaluated publications. Bubble colors represent the averaged citations of the terms.
Table 3. The top 20 recurring keywords.
Keyword Occurrence (% of 18,036 Publications)
Curcumin 9539 (52.9%)
Apoptosis 2223 (12.3%)
In vitro 1909 (10.6%)
Oxidative stress 1834 (10.2%)
Nf kappa b 1558 (8.6%)
Expression 1543 (8.6%)
Cells 1480 (8.2%)
Cancer 1290 (7.2%)
Inhibition 1269 (7.0%)
Activation 1230 (6.8%)
Antioxidant 1108 (6.1%)
Nanoparticles 1021 (5.7%)
Drug delivery 939 (5.2%)
In vivo 880 (4.9%)
Inflammation 808 (4.5%)
Mice 773 (4.3%)
Cancer cells 768 (4.3%)
Gene expression 768 (4.3%)
Alzheimer’s disease 746 (4.1%)
Rats 708 (3.9%)
Molecules 2019,24, 1393 8 of 14
Chemicals that were frequently mentioned in the keywords of evaluated curcumin publications
included, in descending order, curcuminoids (n= 475, citations per publication = 22.4), resveratrol (n=
344, citations per publication = 34.8), chitosan (n= 285, citations per publication = 10.9), flavonoids
(n= 203, citations per publication = 42.6), quercetin (n= 197, citations per publication = 21.3), and
polyphenols (n= 192, citations per publication = 36.8) (Figure 3). In particular, chitosan was outlined
as a useful carrier to deliver curcumin to target cells or sites in the form of nanoparticles [36,37].
Molecules 2019, 24, x FOR PEER REVIEW 8 of 15
Mice 773 (4.3%)
Cancer cells 768 (4.3%)
Gene expression 768 (4.3%)
Alzheimer’s disease 746 (4.1%)
Rats 708 (3.9%)
Chemicals that were frequently mentioned in the keywords of evaluated curcumin publications
included, in descending order, curcuminoids (n = 475, citations per publication = 22.4), resveratrol (n
= 344, citations per publication = 34.8), chitosan (n = 285, citations per publication = 10.9), flavonoids
(n = 203, citations per publication = 42.6), quercetin (n = 197, citations per publication = 21.3), and
polyphenols (n = 192, citations per publication = 36.8) (Figure 3). In particular, chitosan was outlined
as a useful carrier to deliver curcumin to target cells or sites in the form of nanoparticles [36,37].
Figure 3. Chemical structures of key single chemicals or representatives of chemical classes that were
often discussed in the evaluated curcumin publications. The cited compound classes (italic), number
of publications and citations per publication for each chemical or representative chemical class are
given in brackets.
To analyze the temporal changes in the use of keywords, we separated and assessed
publications in four periods: 1989 and before, 1990s, 2000s, and 2010s. Unexpectedly, WoS did not
record any keywords for the papers published in 1989 and before. The top 20 recurring keywords for
each of the remaining three periods are listed in Table 4. It could be observed that antioxidant effects
and cancer remained popular throughout the three periods. Drug delivery, bioavailability, and
Figure 3. Chemical structures of key single chemicals or representatives of chemical classes that were
often discussed in the evaluated curcumin publications. The cited compound classes (italic), number of
publications and citations per publication for each chemical or representative chemical class are given
in brackets.
As over half of the publications were published since 2014, we further analyzed the top 20
keywords used in publications contributed by the top five countries/regions (China, India, the United
States, Iran, and Italy) since 2014 (Table 5). It seemed that the United States and Italy produced more
curcumin-related manuscripts with relevance for Alzheimer’s disease. Manuscripts from Iran and
Italy more frequently referred curcumin-related placebo-controlled and randomized controlled trials.
These five countries quite commonly shared the other top keywords.
Molecules 2019,24, 1393 9 of 14
Table 4. The top 20 recurring keywords in each decade.
1990s Occurrence (%
of 607) 2000s Occurrence (%
of 3683) 2010s Occurrence (%
of 13,636)
Curcumin 140 (23.1%) Curcumin 1490 (40.5%) Curcumin 7909 (58.0%)
Inhibition 37 (6.1%) Apoptosis 442 (12.0%) Apoptosis 1773 (13.0%)
Acid 33 (5.4%) Nf kappa b 383 (10.4%) In vitro 1688 (12.4%)
Tumor promotion 30 (4.9%) Inhibition 355 (9.6%) Oxidative stress 1538 (11.3%)
Activation 28 (4.6%) Expression 306 (8.3%) Expression 1228 (9.0%)
Chemoprevention 28 (4.6%) Activation 298 (8.1%) Cells 1188 (8.7%)
Dietary curcumin 26 (4.3%) Oxidative stress 291 (7.9%) Cancer 1038 (7.6%)
Mouse skin 24 (4.0%) Cells 277 (7.5%) Nanoparticles 1009 (7.4%)
Cancer 23 (3.8%) Gene expression 267 (7.2%) Nf kappa b 987 (7.2%)
Antioxidants 22 (3.6%) Cancer 229 (6.2%) Activation 904 (6.6%)
Curcuminoids 22 (3.6%) Dietary curcumin 224 (6.1%) Antioxidant 889 (6.5%)
Lipid peroxidation 22 (3.6%) In vitro 219 (5.9%) Inhibition 877 (6.4%)
Carcinogenesis 21 (3.5%) Antioxidant 202 (5.5%) Drug delivery 743 (5.4%)
Turmeric 20 (3.3%) Lipid peroxidation 172 (4.7%) In vivo 740 (5.4%)
Colon carcinogenesis 19 (3.1%) Induction 147 (4.0%) Inflammation 706 (5.2%)
Induction 19 (3.1%) In vivo 138 (3.7%) Mice 644 (4.7%)
In vitro 16 (2.6%) Proliferation 133 (3.6%) Bioavailability 610 (4.5%)
Protein-kinase-c 16 (2.6%) Curcuminoids 125 (3.4%) Stability 609 (4.5%)
Cells 15 (2.5%) Mice 116 (3.1%) Rats 588 (4.3%)
Gene expression 14 (2.3%) Chemoprevention 114 (3.1%) Therapy 540 (4.0%)
Table 5.
The top 20 recurring keywords, in descending order, used in the publications contributed by
the top five most productive countries since 2014.
(1) China (2) India (3) USA (4) Iran (5) Italy
Curcumin Curcumin Curcumin Curcumin Curcumin
Apoptosis In vitro In vitro Oxidative stress In vitro
In vitro Nanoparticles Apoptosis In vitro Oxidative stress
Expression Apoptosis Nf kappa b Cancer Nanoparticles
Nanoparticles Oxidative stress Expression Nanoparticles Nf kappa b
Oxidative stress Cancer Oxidative stress Apoptosis Apoptosis
Cells Drug delivery Cancer Cells Drug delivery
Activation Cells Nanoparticles
Placebo-controlled trial
Inflammation
Drug delivery Antioxidant Cells Drug delivery Cancer
Inhibition Bioavailability In vivo Antioxidant Expression
Cancer Delivery Inflammation Inhibition Alzheimer ’s disease
Mice Inhibition Activation Nf kappa b Cells
Inflammation Expression Bioavailability Randomized
controlled trial Randomized controlled trial
Stability Stability Inhibition Double-blind Placebo-controlled trial
Proliferation Derivatives Drug delivery Inflammation Polyphenols
In vivo Cytotoxicity Delivery Therapy Resveratrol
Nf kappa b Nf kappa b Stability Quality of life Therapy
Antioxidant Design Antioxidant Delivery In vivo
Delivery Inflammation Alzheimer ’s disease Expression Double-blind
Therapy Formulation Mice Mice Activation
Since research focused on extracts of the plant Curcuma longa/turmeric is highly relevant and
closely related to curcumin-focused research, an additional analysis was performed to evaluate the
publications that mentioned Curcuma longa or turmeric without mentioning curcumin. A search
was done with the strategy: TOPIC=(“curcum*” OR “tumeric*” OR “turmeric*” NOT “curcumin*”).
We found 3920 publications resulting from this search. The most productive countries were India
(
n= 1041
), China (n= 557), the United States (n= 388), Thailand (n= 286), and Japan (n= 265). The top
five WoS categories were pharmacology and pharmacy (n= 720), food science technology (n= 561),
plant sciences (n= 523), medicinal chemistry (n= 481), and integrative complementary medicine
(
n= 263
). The top 20 keywords from these 3920 publications are listed in Table 6. Keywords from these
publications were more related to plant science studies, concerning the constituents and extracts, as
well as the antimicrobial and antioxidant activity. As expected, there was some overlapping with the
curcumin-focused publications, reflected by common keywords such as apoptosis, inhibition, and
oxidative stress (Figure 4).
Molecules 2019,24, 1393 10 of 14
Table 6.
The top 20 recurring keywords from publications mentioning C. longa or turmeric but
not curcumin.
Keyword Occurrence (% of 3920 Publications)
Turmeric 299 (7.6%)
Curcuma longa 231 (5.9%)
Essential oil 211 (5.4%)
In vitro 205 (5.2%)
Zingiberaceae 198 (5.1%)
Apoptosis 178 (4.5%)
Antioxidant 176 (4.5%)
Antioxidant activity 142 (3.6%)
Constituents 140 (3.6%)
Oxidative stress 131 (3.3%)
Extract 127 (3.2%)
Expression 126 (3.2%)
Antimicrobial activity 118 (3.0%)
Cells 114 (2.9%)
Growth 112 (2.9%)
Curcuma 110 (2.8%)
Inhibition 110 (2.8%)
Rats 102 (2.6%)
Sesquiterpenes 100 (2.6%)
Ginger 93 (2.4%)
Molecules 2019, 24, x FOR PEER REVIEW 11 of 15
Figure 4. Venn diagram comparing the keywords used by curcumin-focused publications and those
used by publications mentioning Curcuma longa or turmeric but not curcumin. Keywords from the
former were more clinically relevant, whereas those from the latter were more related to plant
science studies; commonly used keywords are presented in the middle of the diagram.
4. Discussion
The current study analyzed the curcumin literature with a bibliometric approach. The increased
publication shares from Asian countries in recent years were similarly observed for
antioxidants-related literature [4]. Meanwhile, the huge contributions of the United States, China,
and India were consistent with their dominance in ethnopharmacology research [20]. According to a
previous bibliometric study, Curcuma papers oriented to nutraceuticals and functional foods
research fields received large contributions from the UK and European states [23]. The unique
geographic distribution here, different from bibliometric studies of other scientific disciplines, was
the relatively large contribution from authors affiliated to Japanese and Korean institutions,
especially on its biochemical and therapeutic properties, such as chemopreventive and
anti-amyloidogenic effects [8,38].
Because clinical trials comprised of a small proportion of the curcumin publications analyzed in
the current study, the bubble maps did not show many terms indicative of clinical studies. This is
unlike the situation in neuroscience, where bubble maps clearly showed two clusters of terms, with
one cluster being more related to cellular, molecular, and genetic aspects, and the other one being
more related to clinical aspects [39].
By analyzing the studies describing clinical trial studies of curcumin, we found that oral
curcumin (C3 complex) was a popular theme. Indeed, the C3 complex used in these studies is a
standardized extract of dried rhizomes of C. longa and it represents the most clinically studied form
of curcumin, evaluated in clinical trials in the context of cancer [32,33], but also in multiple other
conditions, including Alzheimer’s disease [40], psoriasis vulgaris [41], oral lichen planus [42],
osteoarthritis [43], inflammation associated with metabolic syndrome [44] and obesity [45], radiation
Figure 4.
Venn diagram comparing the keywords used by curcumin-focused publications and those
used by publications mentioning Curcuma longa or turmeric but not curcumin. Keywords from the
former were more clinically relevant, whereas those from the latter were more related to plant science
studies; commonly used keywords are presented in the middle of the diagram.
Molecules 2019,24, 1393 11 of 14
4. Discussion
The current study analyzed the curcumin literature with a bibliometric approach. The increased
publication shares from Asian countries in recent years were similarly observed for antioxidants-related
literature [
4
]. Meanwhile, the huge contributions of the United States, China, and India were consistent
with their dominance in ethnopharmacology research [
20
]. According to a previous bibliometric
study, Curcuma papers oriented to nutraceuticals and functional foods research fields received large
contributions from the UK and European states [
23
]. The unique geographic distribution here, different
from bibliometric studies of other scientific disciplines, was the relatively large contribution from
authors affiliated to Japanese and Korean institutions, especially on its biochemical and therapeutic
properties, such as chemopreventive and anti-amyloidogenic effects [8,38].
Because clinical trials comprised of a small proportion of the curcumin publications analyzed in
the current study, the bubble maps did not show many terms indicative of clinical studies. This is
unlike the situation in neuroscience, where bubble maps clearly showed two clusters of terms, with
one cluster being more related to cellular, molecular, and genetic aspects, and the other one being more
related to clinical aspects [39].
By analyzing the studies describing clinical trial studies of curcumin, we found that oral curcumin
(C3 complex) was a popular theme. Indeed, the C3 complex used in these studies is a standardized
extract of dried rhizomes of C. longa and it represents the most clinically studied form of curcumin,
evaluated in clinical trials in the context of cancer [
32
,
33
], but also in multiple other conditions,
including Alzheimer’s disease [
40
], psoriasis vulgaris [
41
], oral lichen planus [
42
], osteoarthritis [
43
],
inflammation associated with metabolic syndrome [
44
] and obesity [
45
], radiation dermatitis [
46
], as
well as for modulation of human gut microbiome [
47
]. Moreover, while the low bioavailability of
ingested curcumin had initially limited its clinical usage, a variety of different formulations with
enhanced bioavailability have been recently developed and already studied in multiple clinical
trials [48–50].
We did not analyze the authorship of the curcumin publications. This was because there existed
many Chinese authors who have similar initials that caused inaccurate counting. For instance,
according to the data downloaded from WoS, the most prolific author for the evaluated curcumin
publications was Li Y., which represented Li Yan, Li Yu, and Li Yiwei upon closer examination.
Analyzing authorship by considering authors’ full names was also not viable, because some publication
records only listed author initials.
This study had some limitations, such as the use of a single database (WoS) to collect publications
and their bibliometric data. Additionally, the analysis is of retrospective nature, and due to the fact that
very recent trends (which still did not yield significant number of publications, due to their novelty)
might remain undetected. Moreover, the readers should be reminded that articles mentioning Curcuma
longa or turmeric/tumeric without mentioning curcumin were included in this work as a separate
analysis, presented in Table 6and Figure 4.
5. Conclusions
To conclude, a bibliometric analysis was performed to assess publications on curcumin research.
Our findings have revealed that the United States and Asian countries, such as China, India, Japan,
and South Korea, were major contributors. Most of the publications were focused on biochemistry,
chemistry, oncology, and pharmacology. Over half of the publications were published since 2014,
which mainly focused on the effects of curcumin against cancer, inflammation, and oxidative stress.
Frequently investigated cancer types were breast, colon, colorectal, pancreatic, and prostate cancers.
The large number of publications since 2014 could be attributed to the increased productivity of China
(publications since 2014 = 2443; 68.9% of total contributions) and India (
publications since 2014 = 1620
;
51.8% of total contributions). Drug delivery, bioavailability, and nanoparticles have emerged as
research themes for curcumin research. We expect that future studies should continue to improve
Molecules 2019,24, 1393 12 of 14
delivery or even find new ways to deliver curcumin to target sites, so that more clinical studies can
be supported.
Author Contributions:
A.W.K.Y. and A.G.A. conceived the work, performed data collection, analysis and drafted
the manuscript. All authors critically revised the manuscript draft, and approved the submission of the manuscript.
Acknowledgments:
Atanas G. Atanasov acknowledges the support by the Polish KNOW (Leading National
Research Centre) Scientific Consortium “Healthy Animal—Safe Food,” decision of Ministry of Science and
Higher Education No. 05-1/KNOW2/2015. Andrei Mocan acknowledges the support by the National Research,
Development and Innovations Programme for 2015-2020-PNII, developed with the support of UEFISCDI (Project
No. PN-III-P1-1.2-PCCDI-2017-00473, 8PCCDI).
Conflicts of Interest: The authors declared no conflict of interest.
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