Natural Product Research

Formerly Natural Product Letters

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Natural products in diabetes research:

quantitative literature analysis

Andy Wai Kan Yeung , Nikolay T. Tzvetkov , Alessandra Durazzo , Massimo

Lucarini , Eliana B. Souto , Antonello Santini , Ren-You Gan , Artur Jozwik ,
Weronika Grzybek , Jarosław O. Horbańczuk , Andrei Mocan , Javier
Echeverría , Dongdong Wang & Atanas G. Atanasov

To cite this article: Andy Wai Kan Yeung , Nikolay T. Tzvetkov , Alessandra Durazzo , Massimo
Lucarini , Eliana B. Souto , Antonello Santini , Ren-You Gan , Artur Jozwik , Weronika Grzybek ,
Jarosław O. Horbańczuk , Andrei Mocan , Javier Echeverría , Dongdong Wang & Atanas G.
Atanasov (2020): Natural products in diabetes research: quantitative literature analysis, Natural
Product Research

To link to this article: https://doi.org/10.1080/14786419.2020.1821019

Published online: 07 Oct 2020.

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NATURAL PRODUCT RESEARCH
https://doi.org/10.1080/14786419.2020.1821019

REVIEW

Natural products in diabetes research: quantitative

literature analysis
Andy Wai Kan Yeunga, Nikolay T. Tzvetkovb,c , Alessandra Durazzod ,
Massimo Lucarinid , Eliana B. Soutoe,f , Antonello Santinig ,

czuki,
Ren-You Ganh, Artur Jozwiki, Weronika Grzybeki, Jarosław O. Horban
Andrei Mocan , Javier Echeverr
ıa , Dongdong Wang
j,k l i,m,n
and
Atanas G. Atanasovc,i,o,p
a
Oral and Maxillofacial Radiology, Applied Oral Sciences and Community Dental Care, Faculty of
Dentistry, The University of Hong Kong, Hong Kong, China; bDepartment of Biochemical
Pharmacology and Drug Design, Institute of Molecular Biology “Roumen Tsanev”, Bulgarian
Academy of Sciences, Sofia, Bulgaria; cInstitute of Neurobiology, Bulgarian Academy of Sciences,
Sofia, Bulgaria; dCREA-Research Centre for Food and Nutrition, Rome, Italy; eDepartment of
Pharmaceutical Technology, Faculty of Pharmacy, Polo das Ci^encias da Sa
ude, University of Coimbra,
Coimbra, Portugal; fCEB-Centre of Biological Engineering, University of Minho, Braga, Portugal;
g
Department of Pharmacy, University of Napoli Federico II, Napoli, Italy; hInstitute of Urban
Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China; iInstitute of Genetics and
Animal Biotechnology, Polish Academy of Sciences, Magdalenka, Poland; jDepartment of
Pharmaceutical Botany, Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy,
Cluj-Napoca, Romania; kLaboratory of Chromatography, Institute of Advanced Horticulture Research
of Transylvania, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania;
l
Departamento de Ciencias del Ambiente, Facultad de Qu
ımica y Biolog
ıa, Universidad de Santiago
de Chile, Santiago, Chile; mInstitute of Clinical Chemistry, University Hospital Zurich, Schlieren,
Switzerland; nThe Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,
Guiyang, China; oLudwig Boltzmann Institute for Digital Health and Patient Safety, Medical
University of Vienna, Vienna, Austria; pDepartment of Pharmacognosy, University of Vienna,
Vienna, Austria

ABSTRACT ARTICLE HISTORY

The current study aimed to identify which natural products and Received 3 June 2020
which research directions are related to the major contributors to Accepted 28 August 2020
academic journals for diabetes therapy. Bibliometric data were
extracted from the Web of Science online database using the KEYWORDS
search string TOPIC ¼ (‘‘natural product’ OR ‘‘natural com- Natural product;
pound’ OR ‘‘natural molecule’ OR ‘phytochemical’ OR
phytochemical; diabetes;
bibliometric; citation
‘‘secondary metabolite’) AND TS ¼ (‘diabet’) and analysed by a analysis; curcumin;
bibliometric software, VOSviewer. The search yielded 3694 publi- resveratrol
cations, which were collectively cited 80,791 times, with an H-
index of 117 and 21.9 citations per publication on average. The
top-contributing countries were India, the USA, China, South
Korea and Brazil. Curcumin, flavanone, resveratrol, carotenoid, pol-
yphenols, flavonol, flavone and berberine were the most fre-
quently cited natural products or compound classes. Our results
provide a brief overview of the major directions of natural prod-
uct research in diabetes up to now and hint on promising ave-
nues for future research.

CONTACT Andy Wai Kan Yeung [email protected]; Antonello Santini [email protected]; Atanas G. Atanasov
[email protected]
ß 2020 Informa UK Limited, trading as Taylor & Francis Group
2 A. W. K. YEUNG ET AL.

1. Introduction
Diabetes is a metabolic chronic disease characterised by elevated blood levels of glu-
cose/sugar because the body cannot produce enough insulin or effectively use the
insulin, leading to serious damage to the heart, blood vessels, nerves, eyes and kid-
neys (https://www.who.int/health-topics/diabetes). There are two types of diabetes:
type 1 diabetes (T1DM) and type 2 diabetes (T2DM) (Alberti and Zimmet 1998). T1DM
is characterised by deficient insulin production in the body. The most common is
T2DM (previously known as adult-onset or non-insulin-dependent diabetes), resulting
from the body’s ineffective use (peripheral tissue resistance) of insulin (World Health
Organization 2016). Diabetes is a major public health concern (Zimmet et al. 2016).
According to the Global Report on Diabetes 2016 from WHO, the number of cases as
well as the prevalence of diabetes have been steadily growing over the past several
decades. In total, around 422 million adults were living with diabetes in 2014, in com-
parison to 108 million in 1980 globally. Moreover, 1.5 million deaths were due to dia-
betes in 2012, with an additional 2.2 million deaths because of increasing the risks for
cardiovascular and other diabetes-associated diseases (World Health Organization
2016). T1DM cannot be prevented at present. Although T2DM can be reduced by a
healthy lifestyle, including a healthy diet, exercise and increased physical activity,
avoiding smoking and maintaining a body weight in a healthy range (Lv et al. 2017).
There is a lack of optimally acting drugs with lower side effects to treat it (Souto et al.
2011). Therefore, there is intensive research interest in better understanding diabetes
and finding better treatment options, including the identification of natural products
with anti-diabetic effects (Wang et al. 2014; R
ıos et al. 2015; Souto et al. 2019; Vieira,
Souto, S
anchez-Lo
pez, Lo
pez Machado, Severino, Jose, Santini, Fortuna, et al. 2019;
Vieira, Souto, S
anchez-Lo
pez, Lo
pez Machado, Severino, Jose, Santini, Silva,
et al. 2019).
Many natural products have been used worldwide for controlling blood glucose lev-
els in patients with diabetes. There are several reviews summarising the common nat-
ural products used for managing diabetes (Shapiro and Gong 2002; Tiwari and Rao
2002; R
ıos et al. 2015; Alam et al. 2018; Choudhury et al. 2018; Salehi et al. 2019). For
instance, in Mexico, herbal extracts from Cecropia obtusifolia Bertol. (Cecropiaceae),
 NATURAL PRODUCT RESEARCH 3

Equisetum myriochaetum Schlecht & Cham (Equisetaceae), Leptolobium panamense

(Benth.) Sch.Rodr. & A.M.G.Azevedo (syn. Acosmium panamense (Benth.) Yacolev)
(Fabaceae), Agarista mexicana (Hemsl.) Judd. (Ericaceae), Cucurbita ficifolia Bouch
e
(Cucurbitaceae), Brickellia veronicaefolia (Kunth) A. Gray (Asteraceae) and Parmentiera
aculeata (Kunth) Seem. (Bignoniaceae) are commonly used to lower the blood glucose
level for treating diabetes (Andrade-Cetto and Heinrich 2005). In Sri Lanka, one of the
most frequently used medicinal plants was reported to be Senna auriculata (L.) Roxb.
(Fabaceae) (Sathasivampillai et al. 2017). In South America, Bauhinia forficata Link
(Fabaceae), commonly known as ‘paw-of-cow’, is widely used in ethnomedicine for
therapy of diabetes (Pepato et al. 2002). There also are multiple studies well docu-
menting the role in the treatment of diabetes of Abelmoschus esculentus L. (Moench),
native of Africa, and grown different countries from Africa to Asia, Southern Europe
and America (Dubey and Mishra 2017; Durazzo et al. 2019; Daliu et al. 2020).
The mechanisms of anti-diabetic action include inhibition of a-glucosidase and
a-amylase in the digestive tract, modulation of glucose uptake and the expression of
glucose transporters, stimulation of insulin secretion and pancreatic b-cell proliferation,
control of insulin resistance and regulation of oxidative stress (R
ıos et al. 2015;
Choudhury et al. 2018; Gong et al. 2019). Several anti-diabetic natural product-based
drugs are now available in the market, such as DiabeconV, GlyoherbV and Diabeta
R R

PlusV, with each of them comprised of multiple active ingredients (Choudhury et al.
R

2018). It should be noted that many pieces of evidence for anti-diabetic action of nat-
ural products came from in vitro and in vivo preclinical studies, as Alam et al. (2018)
reported that between 2005 and 2016, there were 63 such studies and only 16 clin-
ical studies.
With the growing number of publications as well as natural products reported to
be useful for treating diabetes, there exists an interest to evaluate the literature in a
quantitative way, so that the most productive contributors, common topics and fre-
quent keywords can be identified. For instance, China and India have a long history of
practicing traditional Chinese medicine and Ayurveda, respectively. According to 2016
data from World Health Organization, they have 1.3 billion population each, with dia-
betes prevalence of 9.4% and 7.8%, respectively (https://www.who.int/diabetes/coun-
try-profiles/en/). As a consequence, are these countries more productive in terms of
publishing papers on natural products in diabetes research? The current study is
aimed to provide an answer to this and other questions along this line. By providing a
quantitative overview of the research literature, researchers may have a better under-
standing of the global research activities in this field, frequently investigated natural
products and leading collaborators.

2. Materials and methods

2.1. Data source
The Web of Science (WoS) online database was queried with the following search
string: TS ¼ (‘natural product’ OR ‘natural compound’ OR ‘natural molecule’ OR
‘phytochemical’ OR ‘secondary metabolite’) AND TS ¼ (‘diabet’). The search identi-
fied publications with a combination of these words or their derivatives in their titles,
4 A. W. K. YEUNG ET AL.

Figure 1. Publication and citation trends of natural products in diabetes research.

abstracts or keywords. The authors’ subscription to the database allows the retrieval of
documents published as early as in 1956. No additional filters were placed on the
search, e.g. publication language, publication type, etc. The identified publications
were initially evaluated with the ‘Analyse Results’ and ‘Create Citation Report’ func-
tions of the WoS platform, and subsequently exported as ‘Full Record and Cited
References’ to VOSviewer (version 1.6.15), a bibliometric software, for further analysis.
As a result, the following parameters were assessed: publication year, publication
count, citation count, authorship, institution, country/region, journal, WoS category,
document type, language.

2.2. Term map

Words from the titles and abstracts were visualised as a term map by VOSviewer with
default settings (Van Eck and Waltman 2010, 2011; Waltman et al. 2010). Terms that
appeared in at least 0.5% (n ¼ 19) of the analysed publications were visualised. Bubble
size represents the number of publications. Bubble colour represents the citations per
publication (CPP). Two bubbles are spatially closer if respective terms co-appeared
more frequently.

3. Results and discussion

The search returned with 3694 publications that were collectively cited 80,791 times,
with an H-index of 117 and 21.9 CPP in general. The earliest indexed document was
published in 1991 in the Journal of Ethnopharmacology and reported the hypogly-
caemic activity of bassic acid, isolated from the rootbark of Sideroxylon obtusifolium
subsp. obtusifolium (Roem. & Schult.) T.D.Penn. (syn. Bumelia sartorum), in diabetic rats
through enhanced secretion of insulin (Naik et al. 1991). The cumulative publication
and citation counts grew steadily in the 2000s and had a much sharper increase in
the 2010s (Figure 1). The growth of citation count was larger than that of publication
count. Meanwhile, 67.7% of the publications were original articles (CPP ¼ 15.3), and
 NATURAL PRODUCT RESEARCH 5

Table 1. Top 5 most productive authors.

Author Publication count (% of total) Citations per publication (CPP)
Gokhan Zengin 36 (0.98) 10.6
Kalidas Shetty 22 (0.60) 79.6
Mohamad F. Mahomoodally 20 (0.54) 7.1
Abdurrahman Aktumsek 15 (0.41) 15.8
Seyed Mohammad Nabavi 15 (0.41) 17.6

29.8% were reviews (CPP ¼ 37.1). Most indexed publications were published in
English (n ¼ 3656; 99.0%), followed by Spanish (n ¼ 15) and Portuguese (n ¼ 8).

3.1. Productive authors

Table 1 shows the top 5 most productive authors. The most productive author was
Gokhan Zengin from Selcuk University, Turkey (n ¼ 36, CPP ¼ 10.6). His most highly
cited paper in the current dataset was a paper that reported the total phenolic con-
tents of extracts of Haplophyllum myrtifolium Boiss. (Zengin et al. 2014). On the other
hand, the author with highest CPP among the top 5 was Kalidas Shetty, with his most
highly cited paper evaluating clonal herbs of Lamiaceae species for inhibiting diabetes
and hypertension-related enzymes (Kwon et al. 2006). It should be noted that ‘Li J’
(n ¼ 28) was originally ranked second by WoS ‘Analyse Results’ function. Upon closer
examination, the record should be a combination of Li Jia who had 13 publications, Li
Jian with 2, Li Jin with 4, Li Jing with 3, Li Jingya with 3 and Li Jun with 3. Similarly,
‘Chen J’, ‘Li Y’ and ‘Kumar A’ ranked 5th to 7th, respectively, by WoS, and were repre-
senting multiple authors, each of whom wrote a few papers only. Therefore, they are
not listed in Table 1.

3.2. Productive institutions

The most productive institution was Chinese Academy of Sciences (n ¼ 84; CPP ¼
21.2). Its most highly cited paper was a review on the resources and biological activ-
ities of natural polyphenols (Li et al. 2014). Besides the top 5 most productive institu-
tions listed in Table 2, there were 7 more institutions with at least 20 publications,
namely National Autonomous University of Mexico (Mexico), Mashhad University of
Medical Sciences (Iran), Tehran University of Medical Sciences (Iran), King Saud
University (Saudi Arabia), King Abdulaziz University (Saudi Arabia), National Taiwan
University (Taiwan, China) and Universiti Putra Malaysia (Malaysia).

3.3. Productive countries/regions

Regarding countries/regions, the most productive was India (n ¼ 717; CPP ¼ 15.3)
(Table 3). The most highly cited paper was a review on the potential health benefits
of plant polyphenols as dietary antioxidants against various diseases including dia-
betes (Pandey and Rizvi 2009). In terms of original research, the most highly cited one
was a report that demonstrated the effect of curcumin on enhancing wound healing
in rats and mice with diabetes induced by streptozotocin and genetic modification,
respectively (Sidhu et al. 1999). Meanwhile, the USA had the highest CPP among the
6 A. W. K. YEUNG ET AL.

Table 2. Top 5 most productive institutions.

Institution Publication count (% of total) Citations per publication (CPP)
Chinese Academy of Sciences 84 (2.3) 21.2
Council of Scientific and Industrial Research (India) 61 (1.7) 25.4
Selcuk University (Turkey) 38 (1.0) 10.2
Shanghai Institute of Materia Medica 38 (1.0) 24.5
Uniersiti Sains Malaysia 38 (1.0) 13.2

Table 3. Top 5 most productive countries/regions.

Country/region Publication count (% of total) Citations per publication (CPP)
India 717 (19.4) 15.3
USA 529 (14.3) 47.4
China 475 (12.9) 17.7
South Korea 228 (6.2) 22.1
Brazil 164 (4.4) 16.5

Figure 2. Publication trend of the top 5 most productive countries/regions.

Table 4. Top 5 most productive journals.

Journal (impact factor) Publication count (% of total) Citations per publication (CPP)
Journal of 135 (3.7) 11.1
Ethnopharmacology (3.414)
International Journal of 98 (2.7) 1.6
Pharmaceutical Sciences and
Research (NA)
Molecules (3.060) 82 (2.2) 17.2
BMC Complementary and Alternative 62 (1.7) 11.4
Medicine (2.479)
Evidence-based Complementary and 61 (1.7) 11.2
Alternative Medicine (1.984)
Not available

top 5 countries. The most highly cited original research was the evaluation study of
Lamiaceae species with Shetty being the corresponding author (Kwon et al. 2006).
Figure 2 shows that the lead by the USA was taken by India since 2014, whereas the
productivity of China has been growing fast and may take the second place in a few
years’ time. The growth rate of South Korea and Brazil seem to be similar.
 NATURAL PRODUCT RESEARCH 7

Table 5. Top 5 most productive WoS categories.

WoS category Publication count (% of total) Citations per publication (CPP)
Pharmacology and pharmacy 1135 (30.7) 21.3
Chemistry medicinal 711 (19.2) 22.6
Biochemistry and molecular biology 516 (14.0) 31.6
Food science technology 455 (12.3) 23.3
Integrative and complementary medicine 386 (10.4) 17.9

3.4. Productive journals

The most productive journal was Journal of Ethnopharmacology (n ¼ 135; CPP ¼ 11.1),
which started to publish 40 years ago (Table 4). Its most cited paper was a review of
the traditional uses of Psidium guajava, including applications for the treatment of dia-
betes (Guti
errez et al. 2008). It should be noted that International Journal of
Pharmaceutical Sciences and Research, the only journal among the top 5 without an
impact factor, had a much lower CPP than the other 4.

3.5. Productive WoS categories

As expected, the largest WoS category for the analysed publications was pharmacol-
ogy and pharmacy (n ¼ 1135; CPP ¼ 21.3) (Table 5). The relatively similar publication
shares of the top 5 categories not only suggested the diverse research directions in
the analysed diabetes literature, but also related to the versatility of the journals, e.g.
Journal of Ethnopharmacology is counted by WoS by 4 categories: pharmacology and
pharmacy, chemistry medicinal, integrative and complementary medicine and plant
sciences. Papers related to biochemistry and molecular biology seemed to have a
higher CPP, consistent to the higher CPP received by Molecules, a major journal in
this category.

3.6. Term map

A total of 1148 terms appeared in at least 0.5% (n ¼ 19) of the 3694 publications and
they are visualised as a term map (Figure 3). It should be noticed that animal studies
(mainly rats and mice, upper part of Figure 3) and content determination studies of
plants (left part) were relatively less cited than the studies involving higher clinical
relevance, particularly those also dealing with co-morbidities other than diabetes, such
as cardiovascular disease and cancer (lower right part). Some highly cited (CPP > 30)
natural products or compound classes included curcumin (n ¼ 100; CPP ¼ 69.1), flava-
none (n ¼ 23; CPP ¼ 49.1), resveratrol (n ¼ 87; CPP ¼ 47.7), carotenoid (n ¼ 72; CPP ¼
44.8), polyphenols (n ¼ 28; CPP ¼ 42.8), flavonol (n ¼ 47; CPP ¼ 39.9), flavone (n ¼ 33;
CPP ¼ 38.5) and berberine (n ¼ 42; CPP ¼ 30.4). Their structures are illustrated in
Figure 4.

3.7. Keyword usage

Over 950 author keywords appeared in at least 3 of the 3694 publications. They cov-
ered a variety of topics, some of which were surrounding diabetes as the popular
8 A. W. K. YEUNG ET AL.

Figure 3. Term map for natural products in diabetes research. Over 1000 terms appeared in at
least 0.5% (n ¼ 19) of the analysed publications. Bubble size represents the number of publications.
Bubble colour represents the citations per publication (CPP). Two bubbles are closer to each other
if the terms co-appeared more frequently.

topics, such as antioxidants, oxidative stress, inflammation and obesity. The top 20
keywords are listed in Table 6. The words ‘flavonoids’ and ‘polyphenols’ were natural
products that were frequently listed as keywords. Pathways related to a-glucosidase
and insulin resistance were frequently investigated.
Some commonly mentioned plant species and family names were Moringa oleifera
(n ¼ 12, CPP ¼ 19.1), cinnamon (n ¼ 8, CPP ¼ 17.8), fenugreek (n ¼ 8, CPP ¼ 12.8),
Lamiaceae (n ¼ 8, CPP ¼ 44.3), Carica papaya (n ¼ 7, CPP ¼ 7.9), Cucurbitaceae (n ¼ 7,
CPP ¼ 31.9), garlic (n ¼ 7, CPP ¼ 18.3), legumes (n ¼ 7, CPP ¼ 61.1), pomegranate
(n ¼ 7, CPP ¼ 35.4), saffron (n ¼ 7, CPP ¼ 15.9) and Stevia rebaudiana (n ¼ 7, CPP
¼ 19.0).

3.8. Comparison with other studies in the literature

The current study evaluated the literature of natural products in diabetes research. We
found that more than 3600 publications investigated on this topic, with the original
article-to-review ratio being 2.3:1. This ratio is larger than that for dietary natural
 NATURAL PRODUCT RESEARCH 9

Figure 4. Chemical structures of selected highly cited natural products.

Table 6. Top 20 most common author keywords.

Keyword Publication count (% of total) Citations per publication (CPP)
Diabetes 468 (12.7) 21.0
Antioxidant 235 (6.4) 22.2
Phytochemicals 221 (6.0) 22.6
Diabetes mellitus 203 (5.5) 15.2
Natural products 155 (4.2) 29.5
Oxidative stress 149 (4.0) 25.9
Flavonoids 133 (3.6) 21.9
Obesity 131 (3.5) 32.3
Inflammation 116 (3.1) 29.0
Antioxidants 110 (3.0) 48.1
Anti-diabetic 109 (3.0) 12.2
Type 2 diabetes 99 (2.7) 23.9
Cancer 98 (2.7) 40.1
a-Glucosidase 96 (2.6) 16.6
Antioxidant activity 94 (2.5) 20.6
Polyphenols 88 (2.4) 39.3
Insulin resistance 86 (2.3) 24.4
Streptozotocin 85 (2.3) 14.4
Medicinal plants 80 (2.2) 16.7
Phytochemical 76 (2.1) 21.0

product research (1.5:1) (Yeung, Aggarwal, et al. 2018), but smaller than natural prod-
ucts in cancer research (4.0:1) (Yeung, El-Demerdash, et al. 2018). Meanwhile, this ratio
seems to be smaller than those of research literatures that are not limited to clinical
relevance, such as antioxidants (12.5:1) (Yeung, Tzvetkov, et al. 2019), curcumin
10 A. W. K. YEUNG ET AL.

(10.4:1) (Yeung, Horban
czuk, et al. 2019) and resveratrol (9.5:1) (Yeung, Aggarwal, et al.
2019). The increasing productivity of India and China in the second half of the 2010s
is similar to the situation in curcumin literature (Yeung, Horban
czuk, et al. 2019).
It is interesting to notice that International Journal of Pharmaceutical Sciences and
Research, which has no impact factor, was the second most productive journal with
CPP ¼1.6. The journal is relatively new, with its first volume published in 2010, and is
open access. Readers can access the full text easily. Perhaps its accessibility can pro-
mote its visibility in the short future so that the papers will be cited more.
Meanwhile, it is reassuring to notice from the term map that studies with higher
clinical relevance tended to be cited more than animal and in vitro studies. This find-
ing seems to be different from a citation analysis on some medical fields, in which
basic research tended to be cited more than clinical research (Van Eck et al. 2013).
Many of the lab studies of natural product and ethnopharmacological research are
antioxidant assays of specimen, such as food and medicinal plants, some of which
may have questionable translational value into clinical settings and are thus rejected
by some journals nowadays (Yeung, Heinrich, et al. 2018). It is expected that in the
future the more clinically relevant studies will continue to get more citations.
Many natural product-derived chemicals are beneficial for managing diabetes,
through various means some of which were identified among the common terms and
keywords, e.g. oxidative stress, cytokine and inflammation, insulin and a-glucosidase
(Alam et al. 2018). Of course, there are many ways to modulate the disease process.
For instance, (poly)phenolic compounds are reported to regulate carbohydrate metab-
olism, improve glucose uptake, protect pancreatic beta cells, enhance insulin action
and regulate signalling pathways to cell homeostasis (Dias et al. 2017).
One of the highly cited natural products was curcumin. In diabetic rats and mice,
curcumin was found to promote wound healing, improve glycemic control and reverse
inflammatory and metabolic derangements (Sidhu et al. 1999; Kowluru and Kanwar
2007; Weisberg et al. 2008). In human randomised controlled trials, consumption of
curcumin was reported to reduce the risk of prediabetic individuals of becoming dia-
betic (Chuengsamarn et al. 2012), lower the atherosclerotic risks in patients with T2DM
(Chuengsamarn et al. 2014) and reduce their inflammatory cytokines and markers of
oxidative stress (Usharani et al. 2008; Panahi et al. 2017). Another highly cited natural
product was resveratrol. It was found to be therapeutic for treating T2DM by being a
SIRT1 and Akt activator that improves glucose homeostasis and insulin sensitivity
(Milne et al. 2007; Brasnyo
et al. 2011; Bhatt et al. 2012). Also, berberine has shown
considerable effectiveness in the management of diabetes and other metabolic dis-
eases in vitro, in preclinical in vivo models and in clinical studies (Neag et al. 2018;
Belwal et al. 2020; Yeung et al. 2020).

3.9. Limitations
One major limitation of the current study is that we only used data from a single data-
base, WoS. Some relevant publications may be indexed by other databases but not in
WoS. However, since each database indexes publications and count citations differ-
ently, it is not possible for us to merge the presented data, especially the citation
 NATURAL PRODUCT RESEARCH 11

data, across multiple databases. Future follow-up studies may consider using data gen-
erated from different databases to compare with the results reported in this study.

4. Concluding remarks
A bibliometric analysis was performed for natural products in diabetes research.
Results showed that the literature grew steadily in terms of publication and citation
counts in the 2000s and has been growing more quickly in the 2010s. The literature
has so far accumulated around 3700 publications. The most productive countries
come from Asia, North and South America. China and India have become more pro-
ductive since the 2010s. The publications were mostly dealing with pharmacology and
pharmacy, medicinal chemistry and biochemistry and molecular biology. Animal stud-
ies and content determination studies of plants were relatively less cited than studies
with direct clinical relevance. a-Glucosidase and insulin resistance were among those
frequently mentioned keywords. Some highly cited natural products or compound
classes included curcumin, flavanone, resveratrol, carotenoid, polyphenols, flavonol, fla-
vone and berberine. Among these, curcumin, resveratrol and carotenoid were more
frequently investigated. However, they have not yet been developed into drugs, with
potential hindrances from low bioavailability (Dei Cas and Ghidoni 2019) reservation
from physicians (Wahner-Roedler et al. 2006) and patenting limitations (Wong and
Chan 2014). We anticipate that future research should further validate the efficacy of
these natural products on managing diabetes through human studies, and to set the
optimal route of administration and dosage, so that the initial promising results can
be readily translated into clinical practice. Along this line, we hope that more future
studies will thus be published in medical journals reporting their potential benefits in
clinical trials.

Author contributions
Conceptualisation, A.W.K.Y. and A.G.A.; methodology, A.W.K.Y. and A.G.A.; data cur-
ation, A.W.K.Y. and A.G.A.; writing-original draft preparation, A.W.K.Y., N.T.T., A.D., A.S.
and A.G.A.; visualisation and validation, all authors; writing review and editing, all
authors. All authors have read and agreed to the published version of the manuscript.

Ethical approval
Not applicable.

Consent to participate
Not applicable.

Disclosure statement
No potential conflict of interes must be reported by the authors.
12 A. W. K. YEUNG ET AL.

Funding
Atanas G. Atanasov acknowledges the support of the Polish KNOW (Leading National Research
Centre) Scientific Consortium ‘Healthy Animal – Safe Food’, decision of the Ministry of Science
and Higher Education No. 05-1/KNOW2/2015. Dongdong Wang acknowledges the Cultivation
project for clinical medicine of the integrated traditional Chinese and western medicine and
Cultivation project for education team of internal medicine of the integrated traditional Chinese
and western medicine in the first-term subjects with special support in the first-class universities
in Guizhou province (Qin Jiao Gao Fa No. 2017-158). Javier Echeverr
ıa gratefully acknowledges
funding from CONICYT (PAI/ACADEMIA No. 79160109).

ORCID
Nikolay T. Tzvetkov http://orcid.org/0000-0002-8482-0481
Alessandra Durazzo http://orcid.org/0000-0002-7747-9107
Massimo Lucarini http://orcid.org/0000-0001-6178-9779
Eliana B. Souto http://orcid.org/0000-0002-9737-6017
Antonello Santini http://orcid.org/0000-0001-5505-3327
Dongdong Wang http://orcid.org/0000-0002-6195-4428
Atanas G. Atanasov http://orcid.org/0000-0003-2545-0967

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