A Recent Report On ‘ Plants With Anti Candida Properties’

International Journal of Current Research and Review

iiaulava@.vaitels
DOI: http://dx.doi.org/10.31782/IJCRR.2020.12186

: A Recent Report on ‘Plants with Anti- Candida
Properties’

Scopus’

IJCRR

Section: Healthcare

Darshan Kumar’, Ayesha2, Madhulika Jha?, Pankaj Gautam’, Himanshu Joshi,
Navin Kumar®

Sci. Journal Impact
Factor: 6.1 (2018)
ICV: 90.90 (2018)

Copyright@IJCRR

"Department of Biotechnology, Graphic Era Deemed to be University, 566/6, Bell Road, Clement Town, Dehradun, Uttarakhand, India;
‘Department of Life Sciences, Graphic Era Deemed to be University, 566/6, Bell Road, Clement Town, Dehradun, Uttarakhand, India;
‘College of Pharmacy, Graphic Era Hill University, Bhimtal Campus, Uttarakhand, India.

ABSTRACT

Fungal infections are drawing attention because of the high mortality and morbidity rate associated with them. Candida, Crypto-
coccus, Pneumocystis, and Aspergillus are the main members of fungal genera responsible for life-threatening fungal infections
all over the world. Candida exists as commensal opportunistic pathogens in the natural flora of human beings. Members of this
genus have specialized virulence attributes which include adhesion, biofilm formation, yeast to hyphal transition, cell surface
hydrophobicity, and secretion of hydrolytic enzymes. C. albicans, C. parapsilosis, C. glabrata, and C. tropicalis are key species,
mainly responsible for 95% of candidiasis worldwide. Azoles, amphotericin B, echinocandins and terbinafine are the main syn-
thetic drugs against the pathogens. Rising resistance to antifungals demands the development of alternative drugs, especially
of plant origin. In this review, we have included the selected plants having significant anti-Candida potential, based upon recent
studies.

Key Words: Candida, Candidiasis, Biofilm, Anti-Candida, Phytoactive, Synthetic drugs, MIC, Camellia sinensis, Hypericum hav-
vae.

INTRODUCTION natural flora of the gastrointestinal tract, the mucosal oral
cavity, and the human reproductive organs comprises of vari-

Fungi are considered to be one of the potential health hazards ous species of Candida’.

to animals including humans. Annually, fungal diseases are
responsible for over 1.5 million deaths and infecting over a
billion people worldwide. Candida, Cryptococcus, Pneumo-
cystisand Aspergillus are the main fungal genera responsible
for such infections'. The occurrence of life-threatening fun-
gal infections has increased in immune-compromised AIDS
patients, blood cancer, neonates, and organ transplants’.
Fungal infections present a possible danger to health world-
wide owing to their elevated mortality and morbidity rate

Candidiasis is a condition of Candida infection which caus-
es shallow mucocutaneous infections, invasive tissue, and
bloodstream infections®’. C. albicans, the most common
pathogenic species, is followed by C. tropicalis, C. glabrata,
and C. parapsilosis*. Clinical isolates have been reported to
be resistant to existing antifungals, particularly azoles, echi-
nocandins, and polyene’. Hydrophobicity of the cell surface,
hyphal transformation hydrolytic enzyme secretion and de-

4, Mortality associated with the fungal disease is similar to
that of tuberculosis (more than 1.6 million) and above 3-fold
more than malaria '.

Candida is a well-known group of fungi containing around
20 pathogenic species. It is a member of the Saccharomy-
cetes class, the Saccharomycetales order, and the Saccha-
romycetaceae family. Ubiquitous, opportunistic, dimorphic,
and commensal fungi are representatives of this group. The

velopment of biofilm over abiotic and biotic surfaces are well
established primary virulence features of the Candida'*".
Most important features of Candida spp. are the ability to
form a biofilm, a three-dimensional multicellular structure
mainly composed of proteins, carbohydrates, phosphorus,
hexosamine, and, uronic acid. Biofilm facilitates adhesion
and maturation on the biotic and abiotic surfaces, ranging
from the mineral surface and mammalian tissues to synthetic
polymers and indwelling medical gadgets, resulting in drug

Corresponding Author:

ISSN: 2231-2196 (Print)
Received: 15.06.2020

ISSN: 0975-5241 (Online)
Revised: 21.07.2020

Navin Kumar, PhD, Professor, Department of Biotechnology, Graphic Era (Deemed to be University), 566/6, Bell Road, Clement Town, Dehradun,
Uttarakhand, PIN-248002, India; Contact: +91-7417325585; +91-135-2642799 (217); Email: navinbajpai@gmail.com; navinkumar.bt@geu.ac.in

Accepted: 25.08.2020 Published: 22.09.2020

Int J Cur Res Rev | Vol 12+ Issue 18 - September 2020

Kumar et al.: Plants with anti-Candida properties’

resistance!?3-!4,

For decades plants have been known as the primary source
of medicinal products among common citizens. Addition-
ally, several countries still used plants as major remedies,
particularly in Africa and Asia. Several plants had exhibited
successful anti-Candida activities which are required to be
tested for efficacy and safety’.

Global burden of candidiasis

Candidiasis is due to the Candida albicans and non-albicans
Candida (NAC) infection, which is mostly known to cause
high rates of mucosal infection to humans worldwide.! Can-
dida infects mucosal tissues, including mouth, oesophagus,
gastrointestinal, vagina, and deep tissue infection'®. Vulvo-

Table 1: Global burden of candidiasis

vaginal candidiasis (thrush or yeast infection) continues to
be a worldwide health problem for women!”!’. Candida in-
fection is common in hospitalized patients having a weak
immune system or immunocompromised patients and el-
derly people !°. More than 30 species of Candida have been
recognized as the causative agent of candidiasis and approxi-
mately 95% of the contaminations are caused by its four spe-
cies: C. albicans, C. parapsilosis, C. glabrata, and C. tropi-
calis ™?,

Nearly 50% of individuals have Candida yeast in the oral
cavity which is responsible for the superficial infection.
However, Candida infection can spread through the body
and can end-up in life-threatening incidences, specifically in
immunocompromised patients 777°.

The global burden of candidiasis is given in Table-1.

Candida spp. related disease. Annual Incidence Global Burden Reference
1. Mucosal
A. Oral candidiasis ~2,000,000 ~2,500,000 1
B. Oesophageal candidiasis ~ 1,300,000 1
C. Vulvovaginalcandidiasis/Recurrent vulvovaginal ~138,000,000 ~372,000,000 17
candidiasis
2. Acute invasive
A. Invasive candidiasis ~750,000 3
3. Candida balanitis 3-4% of uncircumcised males 24

Drug resistance

Azoles and its derivatives (fluconazole, voriconazole, Itra-
conazole, ketoconazole) are primarily used antifungals **”°.
Isolates of Candida have been reported to develop resist-
ance to the existing antifungals (fluconazole, anidulafungin,
caspofungin, micafungin, etc). According to the Centers for
Disease Control and Prevention (CDC, NIH, USA), about
7% of all Candida bloodstream isolates tested at CDC were
resistant to fluconazole and about 1.5% were resistant to
Echinocandin (Figure 1).

(ll

2009 2010 2011 2012 2013 2014 2015 2016 2017
Year

m Fluconazole resistance
E Echinocandin resistance

m Multi-drug resistance

Percent of isolates with resistance
a
Ea

Figure 1: Drug Resistance in Candida sp. isolates during
years, 2009-2017.

(Photo Source: CDC Report)

Increasing resistance to selected drugs encouraged the clini-
cal practice of other drugs also e.g. amphotericin B, echino-
candins, terbinafine, etc. as shown in Table-2 along with its
mode of action.

Plants with anti-candida properties

Plants and their extracts have been used in traditional medi-
cine since prehistoric times due to its availability and effi-
cacy without toxicity”. Plants produce numbers of natural
active compounds for defence against fungi, insects, and her-
bivorous mammals. And many more phytoactive compounds
have biological activities*. The use of herbal medicines has
been widely accepted in many developed and developing
countries. Herbal remedies are widely used in Asia, mainly
India and China, and are now getting popularity in the UK
and Europe, as well as in North America and Australia®*>.
WHO estimated that around 80% population of the develop-
ing countries (like Latin America, Asia, Africa, etc.) depends
on traditional therapy based on herbal medicines for their
primary health care needs. In the year 2000, the global trade
of medicinal plants and their products was reported to be
US$ 60 billion, with a projected forecast to touch US$ 5 tril-
lion by 2050%. India and China are the top global exporters

Int J Cur Res Rev | Vol 12 + Issue 18 e September 2020

Kumar et al.: Plants with anti-Candida properties’

Table 2: Synthetic anti-Candida drugs

S. No. Drug Mechanism of action Reference

1 Amphotericin B Binds to the fungal ergosterol and causes pores in the cell mem- 26, 27
brane.

2 Azoles Inhibits the cytochrome P450 14a-sterol demethylase (CYP51), thus 28,29
the inhibitor of
biosynthesis of ergosterol.

3 Echinocandins Inhibits the 1,3-B-D-glucan, a cell wall component. 27, 30

4 Terbinafine Inhibits ergosterol biosynthesis by inhibiting squalene epoxidase 31, 32

(catalyses the conversion ofsqualene to lanosterol)

of herbal drugs due to its systematic traditional knowledge of
plant-based medicines and culture.

In the modern era, natural products are the source of bioac-
tive substances with possible medical uses in pharmacy and
dentistry. Natural ingredients include essential oils and their
elements and can form part of several classes of compounds,
most commonly phenylpropenes and terpenes with antioxi-
dant, anti-inflammatory, antiseptic, and curative properties
6. Looking at the rising demand for plant-based drugs, we
tried to compile the details of plants showing anti-Candida
properties (Table-3).

Table 3: Plants having anti-Candida properties

Table 3: Plants having anti-Candida properties
Table-3 is an effort to compile some recent studies in the
subject matter in a tabulated form.

Biofilm is an important pathogenic implication of the Can-
dida to survive the existing synthetic drug, which is respon-
sible for drug resistance. Some of the plant extracts and their
phytoactive compounds have exhibited remarkable anti-bio-
film properties; e.g. Berberis vulgaris,” Buchenaviatomen-
tosa Eichler,“ Cinnamomum zeylanicum,” Curcuma longa
L.“ Matricaria chamomilla,” Peganum harmala L.** and
Sanguinaria Canadensis ®'. Berberine, Sanguinarine, Har-

Sr. No. Botanical Natural habitat Phytoactive MIC (ug/ml) Candida species Ref.
Name constituents
1 Acacia dealbata Native to south-eastern Phenolic, Flavonoid, Tannins. 7920+ 1520 C.albicans 37
Australia in New South (ATCC 10231)
Wales, Victoria, Tasmania,
and warm temperate, and
highland tropical landscapes
2 Aframomum Widespread Monoterpenes (Monoterpene 256 C. albicans (ATCC 38
citratum across tropical hydrocarbons, B-Myrcene), 9002)
Africa as well as Oxygen-containing monoter- 1,54 Calbicans (ATCC
on some islands penes (Geraniol) 1663)
of the Indian
Ocean 256 C.albicans IS1
512 C.parapsilosis
1024 C.parapsilosis
(ATCC 22019)
512 C.krusei (ATCC
750)
1024 C.krusei
1024 C.tropicalis (ATCC
750)
2048 C.lipolithica
256 C.haemophilus

Int J Cur Res Rev | Vol 12 - Issue 18 + September 2020

Table 3: (Continued)

Sr. No. Botanical

Name

3 Aframomum
daniellii

4 Allium cepa.

5 Allium hirtifolium.

6 Allium sativum

7 Alpinia galangal L.

8 Aloe barbadensis
Miller

9 Berberis vulgaris

Kumar et al.: Plants with anti-Candida properties’

Natural habitat

West tropical Africa - Sierra
Leone to Central African
Republic, south to Angola.

Worldwide

Asian species of onion
native to central and south-
western Asia.

Native to central Asia and
north eastern Iran

Mediterranean region of
Europe and Africa

Native to central and south-
ern

Europe, northwest

Africa and western Asia

Phytoactive
constituents

Monoterpenes (monoterpene
hydrocarbons, beta- pinene,
limonene), oxygen-contan-
ingmonoterpenes (eucalyptol,
alpha-terpineol), sesquiterpe-
nes (sesquiterpenes hydro-
carbons, trans-beta-caryo-
phyllene), oxygen-containing
sesquiterpenes (caryophyl-
lene oxide)

NR

NR

NR

NR

Eicosyltrifluoroac-etate,
Cyclopropanecarb-oxylic acid,
1-nonadecene,

Cyclopropane, 1-methyl-1-(1-
methyle,

1-undecanol.

Berberine

MIC (pg/ml)

2048

4096

4096

1200-1500

1200-1500

1100-1500

500-800

500-900

1100-1400

1100-1500

64

64

25,000 -50,000

80

20

80

80

Candida species

C.albicans (ATCC
9002)

C.albicans (ATCC
1663)

C.albicans
(IS1)

C.parapsilosis
C.parapsilosis
(ATCC 22019)
C.krusei(ATCC
6258)

C.krusei
C.tropicalis (ATCC
750)

C.lipolithica

C.haemophilus

C. albicans (ATCC
10231)

C. albicans (clini-
cal isolate)

C. albicans (clini-
cal isolate)

C. albicans (ATCC
10231)

C. albicans (clini-
cal isolate)

C. albicans (ATCC
10231)

C. albicans (clini-
cal isolate)

C. tropicalis
(ATCC750)

C. glabrata
(ATCC2001)

C. albicans

C. albicans (ATCC

10231)

C. glabrata
(ATCC 90030)
C. albicans
(clinical isolate)

C. glabrata (clini-
cal isolate)

Ref.

39

39

39

41

42

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Kumar et al.: Plants with anti-Candida properties’

Table 3: (Continued)

Sr. No. Botanical Natural habitat Phytoactive MIC (ug/ml) Candida species Ref.
Name constituents
10 Boswellia carterii NR Essential oils 1250 C. albicans 43
(ATCC10231)
1250-2500 C. albicans
(clinical isolate)
1250 C. tropicalis
(ATCC 750)
1250-2500 C. glabrata
(clinical isolates)
1250 C. krusei
(clinical isolate)
1250 C. albicans
(ATCC10231)
u Buchenavia tomen- NR NR 625 C. albicans 44
tosa, Eichler (SC5314)
12 Calamus leptospadix Native to tropical and Saponin 60 C. albicans 45
Grif subtropical Asia, Africa, (ATCC3007)
& Australia
13 Camellia sinensis NR NR 0.125 C. albicans 46
0.125-0.250 C. tropicalis
0.125 C. parapsilosis
0.125-0.250 C. glabrata
14 Canarium luzonicum Native to the Philippines Essential oils 2500 C. albicans 43
(clinical isolate)
2500 C. albicans
ATCC10231
2500 C. tropicalis
(ATCC750)
2500 C. krusei
(clinical isolate)
2500 C. glabrata
(clinical isolate)
15 Cinnamomum zey- South - West India and a -Pinene, Benzaldehyde, 70 C. albicans (ATCC 47
lanicum Sirlanka 1,8 -cineole, Limonene, Lin- 10231_
A A -Cinnamaldehyde, 1120 C. albicans (ATCC
ugenol, 8
(E)-Cinnamy] acetate. 90028)
<40 C. parapsilosis
(ATCC 90018)
10.45+ 1.00 C. albicans (clini-
cal isolated)
16 Curcuma longa L. Native to the Indian sub- Curcumin 250 C. albicans (ATCC 48,49
continent and Southeast 10261)
Asia 500 C. albicans (ATCC
44829)
500 C. tropicalis
(ATCC 750)
1000 C. albicans

(clinical isolate)

250 C. albicans
(clinical isolate)

500 C. glabrata
(clinical isolate)

Int J Cur Res Rev | Vol 12 - Issue 18 + September 2020

Table 3: (Continued)

Sr. No. Botanical
Name

17 Desmodium gange-
ticum

18 Euphorbia hirta L.

19 Glycyrrhiza glabra L.

20 Hypericum havvae

21 Justicia adhatoda L.

22 Matricaria chamo-
milla

23 Mentha piperita L.

24 Morus alba L.

25 Peganum harmala L.

Kumar et al.: Plants with anti-Candida properties’

Natural habitat

NR

Native to India

native to the Western
Asia and southern Europe

worldwide distribution

The plant's native range is
the Indian subconti-
nent (Nepal , Sri Lanka).

NR

Europe and Middle East

Native to northern Chi-
na and India

NR

Phytoactive
constituents

Flavonoids, Glycosides,
Saponins
,Tanins

Free flavonoids,
Bound flavonoids

Glabridin

Phenolic compounds (hy-
pericin, hyperforin)

Vasicine, a quinazoline

alkaloid.

Essential oil

Essential oil

Flavonoids,
Tannins and
Triterpenes

Harmaline

MIC (pg/ml)

31.2

39-156

1250

1250

625

3120

6250

6250

12500
25000
25000

14.8+0.2

1.50 + 0.16

1024

62.52.04

Candida species

C. albicans (MTCC
F7315)

C. albicans
(MTCC183)

C.albicans
(MTCC 1637)

C.albicans (clini-
cal isolates)

C. pseudotropi-
calis (clinical
isolates)

C. albicans (ATCC
10231)

C. tropicalis
(ATCC 13808)

C. guilliermondii

(ATCC 6260)
C. krusei

C. glabrata
C.parapsilosis

C.albicans

C. albicans

(ATCC18804)

C.albicans
(ATCC26790)

C. albicans
(ATCC-76645)

C. albicans (LM-
106)

C.tropicalis
(ATCC-13083)

C.tropicalis (LM-
6)

C.krusei(LM-656)

C. albicans (ATCC

10231)

Ref.

53

58

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Kumar et al.: Plants with anti-Candida properties’

Table 3: (Continued)

Sr. No. Botanical Natural habitat Phytoactive MIC (pg/ml) Candida species Ref.
Name constituents
26 Retama raetam Native to northern Africa Isoflavone (Derrone) 7.81 C.albicans (ATCC
from the Western Sahara 90028)
7.81 C. glabrata (ATCC
90030)
7.81 C.parapsilosis
7.81 (ATCC 22019)
C. kreusei (ATCC
7.81 C.albicans (ATCC
90028)
Licoflavone C 15.62 C. albicans (ATCC
90028)
15.62 C. glabrata(ATCC
90030)
15.62 C.parapsilosis
(ATCC 22019)
15.62 C.kreusei (ATCC
6258)
27 Rhizoma coptidis Native to China NR >1024 C. albicans(ATCC 40
14053)
128 C. tropicalis
(ATCC 750)
64 C. glabrata (ATCC
2001)
>1024 C. krusei (ATCC
6258)
28 Ruta graveolens L. It is native to the Balkan Volatile oils 35.10 + 0.02 C.albicans (ATCC 60
Peninsula 26790)
29 Sanguinaria canaden- Native to eastern North Sanguinarine 4 C. albicans 61
sis America (SC5314)
30 Sapindus saponaria L. Native to the Americaand Carbohydrates and triterpe- 300-600 C. albicans (ATCC 62
India nes 90028)
300-600 C. albicans

(clinical isolate)

600 C. glabrata
(clinical isolate)

31 Scutellaria baicalensis Nativeto Baicalein B C. albicans (ATCC 63
China, Korea, 64548)
Mongolia, and Russia 26 C. albicans (ATCC
64550)
104 C. tropicalis
(186.06)
52 C. tropicalis
(ATCC 200956)
13 C. parapsilosis
(ATCC 22019)
13 C. parapsilosis
(153.07)

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Kumar et al.: Plants with anti-Candida properties’

Table 3: (Continued)

Sr. No. Botanical Natural habitat Phytoactive MIC (ug/ml) Candida species Ref.
Name constituents
32 NA NA Eugenol 625 C. albicans 64
(SC5314)
625 C. auris
33. NA NA Methyl Eugenol 1250 C. albicans 64
(SC5314)
1250 C.auris
34 NA NA Thymol 625 C. albicans 64
(SC5314)
312 C.auris
35 NA NA Carvacrol 250 C.albicans 64
(SC5314)
125 C.auris
36 Unonopsis duckei NR Polycarpol 250 C.albicans 65
(ATCC 10231)
250 C. albicans
(ATCC 1023)
250 C.dubliniensis
(ATCC 778157)

*NA: Not applicable; NR: Not reported

maline, Curcumin, and many other phytoactive compounds
have been reported to decrease the viability of Candida bio-
film significantly*48461,

CONCLUSION

Since the prehistoric period, plants have been the source of
medicine in different countries like India and China. Ac-
cording to a WHO report, approximately 80% of the premier
health issues in developing countries depend on traditional
medicine. Currently, the scientific research community and
government health agencies are focusing on the studies re-
lated to the bioactive compounds. Phytoactive compounds
are generally safe and easily available for commercial-scale
drug production. Therefore, it’s encouraging to develop an
effective and safe drug against microbial human pathogens
from natural resources. Nature holds ample resources for
the discovery of new and highly effective herbal drugs. It
may be concluded from the table-3 that two plants Camellia
sinensis and Hypericum havvae have remarkable anti-Can-
dida properties and can be used to develop alternative anti-
Candida drugs. Camellia sinensis have shown promising
results against many pathogenic species of the Candida e.g.
C. albicans, C. parapsilosis, C. Tropicalis, and C. Glabrata,
and Hypericum havvae was effective against C. glabrata, C.
kreusei, C. parapsilosis, C. guilliermondii, and C. tropicalis.

Acknowledgement: Authors acknowledge the immense
help received from the scholars whose articles are cited and
included in references of this manuscript. The authors are

also grateful to authors / editors / publishers of all those ar-
ticles, journals and books from where the literature for this
article has been reviewed and discussed.

Source(s) of Funding: No funding is involved.

Conflicting Interest: The authors declare no conflicting in-
terest.

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