Herbal Hsu MRIMC 2020

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Mini-Reviews in Medicinal Chemistry, 2020, 20, 000-000 1
SYSTEMATIC ARTICLE
Herbal Extracts with Antifungal Activity against Candida albicans: A Sys-

tematic Review
Hsuan Hsu1, Chirag C. Sheth2 and Veronica Veses3,*
1
Department of Dentistry, Faculty of Health Sciences, Universidad Cardenal Herrera, CEU Universities, Moncada
46113, Valencia, Spain; 2Department of Medicine, Faculty of Health Sciences, Universidad Cardenal Herrera, CEU
Universities, Moncada 46113, Valencia, Spain; 3Department of Biomedical Sciences, Faculty of Health Sciences,
Universidad Cardenal Herrera, CEU Universities, Moncada 46113, Valencia, Spain
Abstract: In the era of antimicrobial resistance, fungal pathogens are not an exception. Several strate-
gies, including antimicrobial stewardship programs and high throughput screening of new drugs, are
being implemented. Several recent studies have demonstrated the effectiveness of plant compounds
with antifungal activity. In this systematic review, we examine the use of natural compounds as a pos-
ARTICLE HISTORY
sible avenue to fight fungal infections produced by Candida albicans, the most common human fungal
pathogen. Electronic literature searches were conducted through PubMed/MEDLINE, Cochrane, and
Science Direct limited to the 5 years. A total of 131 articles were included, with 186 plants extracts
evaluated. Although the majority of the natural extracts exhibited antifungal activities against C. albi-
Received: February 20, 2020
Revised: May 19, 2020 cans (both in vivo and in vitro), the strongest antifungal activity was obtained from Lawsonia inermis,
Accepted: May 21, 2020
Pelargonium graveolens, Camellia sinensis, Mentha piperita, and Citrus latifolia. The main compo-
DOI: nents with proven antifungal activities were phenolic compounds such as gallic acid, thymol, and fla-
10.2174/1389557520666200628032116
vonoids (especially catechin), polyphenols such as tannins, terpenoids and saponins. The incorporation
of nanotechnology greatly enhances the antifungal properties of these natural compounds. Further re-
search is needed to fully characterize the composition of all herbal extracts with antifungal activity as
well as the mechanisms of action of the active compounds.
Keywords: Herbal extracts, antifungal properties, Candida albicans, gallic acid, thymol, catechin, nanotechnology.
1. INTRODUCTION Candida tropicalis, Candida parapsilosis, and Candida

krusei, which comprised up to 90% of Candida infections
Candida species are commensal microorganisms in hu- [2]. It is estimated that more than a quarter of a million pa-
man oral mucosa, digestive and vaginal tracts. Normally,
tients are infected with invasive candidiasis, with the inci-
people with healthy immune systems can control the growth
dences rates up to 2-14 per 100000 populations globally [3].
and spread of this opportunistic fungus. However, when the
In addition, Candida is ranked fourth of the most common
host becomes weak and immunocompromised, it can lead to
pathogens of bloodstream infections after Staphylococcus
serious infection. These infections can be superficial such as
aureus and Enterococci [4]. Furthermore, C. albicans is one
thrush, vaginitis, skin infections, or invade the bloodstream of the most isolated species responsible for nosocomial in-
and spread to any site of the human host, which can cause
fections due to the use of intravenous catheters, invasive
many clinical complications such as brain abscess, endocar-
procedures, transplantation, wide range use of broad-
ditis, meningitis, arthritis and pyelonephritis [1].
spectrum antibiotics and chemotherapies [2]. Particular char-
Approximately 150 Candida species have been identified, acteristics of C. albicans are their morphological transition
of which only about 20 species can cause infection in humans. between yeast and hyphal forms, which allow adherence to
Among these, Candida albicans is the most common patho- oral mucosa; formation of biofilms; phenotypic switching
genic species responsible for most invasive infections in im- and the secretion of virulence factors such as adhesins and
munocompromised patients, followed by Candida glabrata, hydrolytic enzymes [5].
Currently, there are only five major classes of antifungal
*Address correspondence to this author at the Department of Biomedical agents available to treat C. albicans infections. These include
Sciences, Faculty of Health Sciences, Universidad Cardenal Herrera, CEU polyenes, allylamines and azoles, which target ergosterol and
Universities, Moncada 46113, Valencia, Spain; Tel: +3496136900 ext nucleoside analogues, which inhibit DNA and/or RNA syn-
64351; E-mail: veronica.veses@uchceu.es
1389-5575/20 $65.00+.00 © 2020 Bentham Science Publishers

2 Mini-Reviews in Medicinal Chemistry, 2020, Vol. 20, No. 0 Hsu et al.
thesis, and echinocandins, that inhibit the synthesis of β-1, 3- terms: (C. albicans) AND extracts [MeSH Terms]) OR natu-
glucan [6]. Among these, azole antifungals such as flucona- ral products [MeSH Terms]) OR herbal [MeSH Terms])
zole are often selected as the treatment choice because they AND antifungal [MeSH Terms]) were searched in PubMed
are well tolerated, exhibit low toxicity, available for oral in the English language.
administration, and are inexpensive. However, in recent
years, the resistance of Candida species to antifungal drugs 2.2. Inclusion Criteria
has increased worldwide [7]. Generally, antifungal resistance
is achieved through reduced intracellular drug accumulation, The fundamental inclusion factors were that the studies
decreased target affinity for the drug and counteraction of the must involve the use of natural products, herbs, or extract
drug effect. against C. albicans. Studies could be either in vitro, in vivo,
or both for the purpose of assessing the antifungal activity of
Due to the widespread and overuse of limited antifungal natural products against C. albicans. Table 1 shows all the
drugs, the search for alternatives against C. albicans is ongo- study inclusion and exclusion criteria.
ing, especially in plants and natural herbs. It is estimated that
there are 250,000-500,000 species of plants on earth and 2.3. Types of Study
only 10% are used by humans [8], which provided 50% of
commercially available modern drugs [9]. Plant extract ther- All prospective or longitudinal studies, experimental
apies have been utilized and accepted all over the world due studies, clinical trial/study, double-blinded, randomized,
to their low side effects. The earliest record of plant medica- placebo-controlled trials examining nature were included.
tions can be traced back to 2600 BCE in Mesopotamia,
Egypt, India, Greece and China, revealing about 300-1000 2.4. Types of Preparation
different drugs [9]. The most common species used by an-
cient people are algae, bryophytes, pteridophytes and angio- Herbal preparations are described as naturally prepared
sperms [9]. Different geographical locations also have a big from herbs or plants from their roots, flowers, leaves, fruits,
impact on the development of herbal drug systems and the bulbs or seeds through different extraction methods into es-
availability of plant resources. Kier and coworkers describe sential oil or extracts. These were then applied to inactive
that the highest diversity of plants may be found in the Neo- placebo or active control such as common antifungal drugs
tropic (central and south America) and the Asia-Pacific re- (azoles, nystatin, amphotericin B). Studies combining herbal
gion (China, India, USA, Australia), and lower diversities in interventions and routine pharmacologic therapy (co-
Africa and on oceanic islands [10]. Traditionally, the majori- intervention) were also reviewed.
ty of medicinal plants are found in India and China, while
Europe and the USA have developed fewer sources [9]. The 2.5 Selection Criteria
diversity of plants provides a wide range of important
sources of biologically active molecules with enormous po- Studies omitted from this review include retrospective
tential antifungal properties, such as phenols, tannins, terpe- studies, editorials, letters, reviews, case reports, cohort stud-
noids and alkaloids [9]. Isolated and modified compounds ies and pilot studies. Studies not using C. albicans as a tested
such as dimethyl pyrrole, hydroxydihydrocornin-aglycones organism and not presenting minimum inhibitory concentra-
and indole derivatives have also shown antifungal activity in tion values (MIC) were also excluded. Essential oils and
vitro [8]. Studies have reported that the extraction method of extracts originating from animals or insects were excluded
active substances has a great influence on the function of from this study.
antimicrobial components and their antifungal effectiveness.
Silver nanoparticles, antibodies, and photodynamic inactiva- 2.6. Study Selection
tion have increased the distribution and effectiveness of anti-
Firstly, primary literature research was conducted. Next,
fungal drugs [2]. For this reason, the antifungal activity of
the abstracts and titles were evaluated in order to screen and
natural herbs and extracts have been assessed as an alterna-
eliminate articles unrelated to this research topic. Following
tive antifungal drug against C. albicans. In this systematic
this, the remaining studies were downloaded as full-text arti-
review, we evaluate the antifungal activities of natural herbs
cles and were assessed for eligibility. Only studies meeting
and extracts and their synergistic effect with common anti-
fungal agents. the inclusion and exclusion criteria were included in this
systematic review.
2. MATERIALS AND METHODS
2.7. Data Extraction
2.1. Search Strategy
Tables 2 and 3 were used to organize the information
This review was carried out in accordance with PRISMA gained from each study [11-19]. Table 2 displays data from
guidelines. Comprehensive, structured literature searches combined in vivo/in vitro studies whilst Table 3 contains
were conducted via the databases PubMed/MEDLINE, information from in vitro studies only [20-141]. The follow-
Cochrane and Science Direct. The publication date was lim- ing data was collected from all eligible articles: the scientific
ited from Jan 1st, 2015 until Feb 23rd, 2019. The electronic and common names of the plants; country of collection; parts
search was performed using the phrases: C. albicans AND of the plants that were extracted; extraction methods; strains
(extract OR herbal OR natural) AND (antifungal) for Sci- that were tested; MIC or colony-forming units (CFU) of the
ence Direct and Cochrane Library; Search terms with Mesh products and outcomes.
Antifungal Herbal Extracts against Candida albicans Mini-Reviews in Medicinal Chemistry, 2020, Vol. 20, No. 0 3
Table 1. List of inclusion and exclusion criteria.
Inclusion Criteria Exclusion Criteria
Study type: prospective or longitudinal studies, experimental studies, Clinical Trial, Retrospective study, editorials, letters, review, case report, cohort,
Clinical study, RCT (Only articles with level of evidence of 1b are included) pilot study
C. albicans strains must be tested Algae/Animal/Insects as interventions.
Results must include antifungal assessment/evaluation method using MIC in vitro

Studies in which C. albicans are not tested.
and in vivo. CFU unit is also included in in vivo studies.
Full length article available -
English-language only -
Published between Jan 1,2015 to Feb 23rd, 2019 -
Studies combined natural products with common antifungal drugs are included
-
(Nystatin and azoles)
Table 2. Data extraction table from combination in vivo/in vitro studies investigating the antifungal activity of plant extracts against
C. albicans.
In vivo:
In vitro: MIC
Plant/Organism Country Plant Product MIC /CFU Host
Refs. (mg/mL, Strains Conclusion
(Common Name) of Origin Part(s) (s) (mg/mL, Organism
mg/mL)
mg/mL)
[11] Lawsonia inermis Iran Leaves EE 5-10 mg/mL - Wistar rats C. albicans 4% was more effective
LC201976 than 2% and was as effec-
tive as clotrimazole.
[12] Punica granatum L. Algeria - AC 80 mg/mL 0.090 mg/mL Male mice C. albicans Quercus suber L. show the
C. krusei best and Vicia faba had the
Quercus suber L. 20 mg/mL 0.105 mg/mL
C. guillier- poor antifungal activity.
Vicia faba >100 mg/mL 0.010mg/mL mondii
[13] Camellia sinensis Algeria - AC 40 mg/mL 5 µg /mL C57BL6 C. albicans, AC was more active
(L.) O Kuntze mice C. glabrata,
AQ 60 mg/mL 20 µg /mL
C. tropicalis,
C. krusei
[14] Morinda tomentosa Indonesia Roots ME >32mg/mL - Galleria C. albicans x

mellonella DSY2521
C. albicans
CAF2-1
[15] Melaleuca Brazil - Essential 5.33 Log10 1.95 mg/mL Male mice C. albicans • 12.5% extract concen-
alternifolia oil CFU strain ATCC tration completely inhi-
18804 bited the biofilms
• Protective effect against
oral C. albicans infec-
tions in mice.
[16] Mitracarpus Brazil Aerial ME 400 and 500 µg /mL Female C. albicans • Promising antifungal
frigidus 4000mg kg−1 Wistar rats ATCC activity in vitro and in
CFU: Log 4.68 10231 vivo.
(day one) • In vitro results suggest
its ability to act on the
cellular envelope.
• Better than fluconazole
(MIC value = 10,000µg
/mL)
(Table 2) Contd….
In vivo:
In vitro: MIC
Plant/Organism Country Plant Product MIC /CFU Host
Refs. (mg/mL, Strains Conclusion
(Common Name) of Origin Part(s) (s) (mg/mL, Organism
mg/mL)
mg/mL)
[17] Syzygium cumini Brazil Seeds NaP 100mg/kg - Diabetic - • Nanotechnology impro-
infected ve antioxidant proper-
Wistar rats ties.
• Contain high concentra-
tions of phenols and
flavonoids (gallic acid,
chlorogenic acid, grutin,
quercetin)
• Hypoglycaemic activity
in rat models of DM
[18] Astragalus China Roots Low CFU: 5.87 ± - Sera of mice - Greatly improved against
membranaceus molecular 0.03c -6.05 infected systemic candidiasis by
weight log10 with live strongly enhancing Th1
polysac- C. albicans and Th2 responses in re-
charide cells combinant protein rP-
(LMW- HSP90C, but mechanism is
ASP) unclear.
[19] Jatropha curcas L Mauritius Barks, Crude 350-3290 mg/L 17.80-83.30 Bactrocera C. albicans • Show antifungal activity
roots extracts mg/mL zonata and ATCC 1023 in vivo and in vitro.
leaves, B. cucurbitae • ME of mature leaves
seeds (Diptera fruit show the lowest activity
flies) and bark ME extract
was highest in vivo.
• Contains alkaloid, ste-
roids, tannins, flavo-
noids, phenol and cou-
marins.
Abbreviations: *-: Not specified/Not available, *X: No antifungal effect; *ME: Methanolic extract, * AC: Acetone extract, *AQ: Aqueous extract, *AQE: Aqueous ethanolic extract;
*EtOAc: Ethyl actetate extract, * EE: Ethanol extract, *Dichloromethane extract: DCM , *HE: Hexane extract; *CHL:Chloroform extract , *BA: butanol extract; *NaP: Nanoparti-
cles/Nano formulations.
2.8. Antifungal Activity Measurement lowing the screening of titles and abstracts, 2283 articles
were excluded, leaving 379 full-text articles, which were
Both in vitro and in vivo antifungal activities are meas-
assessed for eligibility. Finally, a total of 131 articles met the
ured by Minimum Inhibitory Concentration (MIC), which is inclusion criteria and were considered suitable for this sys-
defined as the lowest concentration of an antimicrobial drug
tematic review. In total, there were 186 natural products in-
that will inhibit the visible growth of a microorganism after
volved in this systematic review; please see Tables 2 and 3
overnight incubation. Antifungal activities are measured
for further details on each study, [11-19] [20-141]. Plants
either by microdilution assay, tube diffusion method or serial
identified in the review originated in 42 countries, with the
microplate dilution methods. In addition, in vivo studies are
largest percentages in Brazil (20%), India (9%) and Iran
also assessed by quantifying the CFU, which is a measure (7%) (Fig. 2). This geographical distribution and preference
used to estimate the number of viable bacteria or fungal cells
are supported by a study by Kier and coworkers [10].
in a sample.
Most herbal extracts show minimal to moderate antifun-
2.9. Data Quality Evaluation gal effects against C. albicans; however, 27 tested plants
were ineffective against it. In terms of herbal interventions,
The quality of studies was evaluated according to the
seven studies utilized nanotechnology with herbal extracts;
Centre for Evidence-based Medicine Levels of Evidence and
PRISMA guidelines [149,150]. ten articles assessed the synergistic effect of natural products
with common antifungal drugs. Fourteen plants have been
3. RESULTS AND DISCUSSION tested repeatedly in several studies and appear more than
once in this review, which are Salvadora persica, Camellia
3.1. Description of Selected Reports sinensis, Cinnamomum verum, Cuminum cyminum, Law-
Fig. (1) depicts an overview of the study selection proce- sonia inermis, Melaleuca alternifolia, Mentha piperita, Ori-
dure. After the removal of duplicates, a total of 2666 articles ganum vulgare, Paeonia lactiflora, Pelargonium graveolens,
were recovered from three databases, with publication dates Psidium guajava, Syzygium aromaticum and Thymus vulgar-
ranging from January 1, 2015, to February 23rd, 2019. Fol- is.
Table 3. Overview of names, countries of origin, plant part(s), formulation, MIC, strains used and conclusions of the herbal inter-
ventions in vitro.
Country MIC (mg/mL,

Refs. Plant/Organism Plant Part(s) Formulation Used Strains Conclusion
of Origin mg/mL)
[20] Olea europaea Croatia Leaves Extract 46.875 mg/mL C. albicans • Cytotoxic effect on tested
(Olive) ATCC 10231 yeast strains
C. dubliniensis
• Concentration dependent.
CBS 7987
• Contains hydroxytyrosol,
protocatechuic acid, tyrosol,
oleuropein, pinoresinol and
apigenin.
[21] Melaleuca Australia Leaves Tea tree oil Average 0.19% C. albicans ATCC Show antifungal and synergistic
alternifolia (TTO) Fluconazole +TTO: 10231 effect with fluconazole
38.46mg/mL C. albicans strains
resistant to flucona-
zole
[22] Stryphnodendron Brazil Stem barks Dried and 15.6 µg/mL C. albicans Successfully inhibited plankto-
adstringens pulverized ATCC 10231 nic growth and biofilm develo-
(Mart.) Coville pment.
(Leguminosae)
[23] Metasequoia Korea Cone (abietane- EtOAc 250-1000(mg/mL) C. albicans Effective against C. albicans
glyptostroboides type diterpenoid KBN06P00076
taxodone) C. Albicans
KBN06P00074
24] Eugenia dysenteri- Brazil Leaves AQ Cannot be detected C. guilliermondii • No inhibition detected against
ca DC. (Hexach- ATCC 6260, C. Albicans and C. Glabatra.
lamys macedoi C. tropicalis
• AQ show significant inhibi-
Legrand) ATCC 28707
tory activity against C. Para-
Pouteria ramiflora C. parapsilosis
psilosis, C. Guilliermondii, C.
(Mart.) Radlk, ATCC 22019
Tropicalis, C. Krusei and C.
Pouteria torta C. albicans Famat.
(Mart.) Radlk, ATCC 90028,
Bauhinia rufa C. Glabrata
(Bong.) Steud, ATCC 2001,
Erythroxylum C. Famata
subrotundum A ATCC 62894
C. krusei
ATCC 34135
[25] Piper guineense Nigeria Fruits and AQ AQ: NA C. albicans ME, EE, CHL and HE show
leaves EE EE:78 µg/mL ATCC 10231 antifungal efficacy, whereas AQ
ME ME:39 µg/mL C. Glabrata is not effective.
CHL CHL:78 µg/mL ATCC 2001
HE HE:78 µg/mL C. Tropicalis
ATCC 750
C. Parapsilosis
ATCC 7330
[26] Pelargonium USA Purchased Geranium oil GO:1.82 µg/mL C. albicans • NGE was twice higher uv
graveolens (GO) NGE:3.64 µg/mL ATCC 14053 the GO and uve le to redu-
Nanoemulsion C. Tropicalis ce the amount of biofilm in
geranium oil ATCC 66029 the catheter.
(NGE) C. Glabrata
• Eliminate biofilm formation.
ATCC 66032
C. Krusei
ATCC 6258
[27] Swartzia simplex Panama Root and bark DCM 32 µg/mL C. albicans DSY2621 Show antifungal activity
Parent wild-type
CAF2-1
[28] Bursera Mexico Stems Ramirez 0.062 – 0.25 mg/mL C. albicans Germ uve inhibition and dimi-
morelensis essential Oil ATCC 14065 nish the transcription of the gene
C. Albicans INT1.
ATCC 32354
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[29] Aeollanthus Cameroon Hexane ethyl 0.625 - 5 mg/mL C. albicans Biofilm inhibition by blocking
cucullathus acetate extract C. glabrata. the filamentation process and by
reducing the biofilm thickness.
[30] Leguminosae Brazil Leaves ME - C. albicans None of them show antifungal
family species C. krusei activity.
C. glabrata
C. tropicalis
C. parapsilosis,
[31] Ricinus communis Ghana leaves AQ 3.13 - 25.0 mg/mL C. albicans. • All are effective against C.
ME albicans,
EE
• ME show higher antifungal
activity than other extract.
may be due to the presence of
high amount of tannins,
flavonoids, and terpenoids.
[32] Cochlospermum Brazil Pilger roots EtOAc 250 mg/mL C. albicans 10231 Effective due to the presence of
regium C. krusei 34135 tannins and gallic acid.
C. glabrata 2001
C. tropicalis 28707
[33] Salvia adenophora Italy Aerial Isolated - C. albicans clinical X
Fernald (Lamia- compounds strain.
ceae)
[34] Olea africana South Leaves HE Average C. albicans All are effective however C.
Africa CHL 0.37 mg/mL neoformans and E. faecalis were
DCM, the most sensitive test orga-
EtOAc nisms.
EE
ME
BA
AQ
35] Helichrysum Turkey - EE All are 8 µg /mL C. albicans H. arenarium is the most remar-
species: C. parapsilosis kable among other tested ex-
H. armenium DC, tracts.
H. arenarium L.
(Moench)
[36] Antidesma mada- Mauritius Leaves AQ 4.00 mg/mL C. albicans Show antifungal activity and
gascariense Lam. AC ATCC 10231 show antioxidant, anti-
(Euphorbiaceae) inflammatory activity and serve
as AChE inhibitors.
[37] Lavandula Iran Aerial parts Essential oils 7.91 mg/ mL C. albicans isolates • Effective against C. albicans.
binaludensis
• Antifungal are attributed to g-
Cuminum cyminum terpinene and 1,8-cineole
through destroying cell walls
8.00 mg/mL and proteins, interfering in
the work of membrane enzy-
mes and affecting DNA and
RNA replication.
[38] Lawsonia inermis India Leaves ME ME:2.8 mg/mL C. albicans W. somnifera, C. longa, Euphor-
EE bia hirta, Echinophora platybo-
Withania somnife- ME: 3.2 mg/mL la, Zingiber officinale, L. iner-
ra EE: 3.1 mg/mL mis, Adenocalymma alliacum,
Curcuma longa ME:5.0 mg/mL P. parviflorus and Swertia chira-
EE: 2.81 mg/mL ta effective against C. albicans
at MIC 5 mg/mL without any
Euphorbia hirta ME:1.5 mg/mL toxic effect.
EE: 2.75 mg/mL
Pogostemon parvi- ME: 4.3 mg/mL
florus EE: 4.25 mg/mL
Adenocalymma ME: 3.15 mg/mL
alliacum, EE: 3.85 mg/mL
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
Echinophora EE: 2.3 mg/mL

platybola
Zingiber officinale ME: 2.10 mg/mL
EE: 4.25 mg/mL
39] Thymus capitatus Tunisia Aerial parts Essential oils 125 µg/mL C. albicans 328, • C. verum exhibited the best
C. albicans 247, activity; S aromaticum
Pelargonium 250-1000 µg/mL C. albicans 311, showed moderate. activity;
graveolens C. albicans 249, P. graveolens EO was less
Cinnamomum 31.25-62.5 µg/mL C. riferii 648, active.
verum C. tropicalis,
• Affect ergosterol biosynthesis
C. glabrata 239,
and disturb fatty acid ho-
Syzygium 125-250 µg/mL C. glabrata 113
meostasis.
aromaticum
[40] Sideroxylon Brazil leaves Hydro alco- 62.5 mg/mL C. albicans Show antifungal activity in the
obtusifolium holic extracts ATCC 10231 presence of flavonoid and sapo-
nins.
Syzygium cumini
125 mg/mL
[41] Polyscias fulva Cameroon Stem bark Crude 12.5 µg/mL C. albicans Show antifungal activity due to
(Hiern) DCM 50 µg/mL ATCC 1663 the presence of terpernoid and
C. Krusei saponins
ME 100 µg/mL ATCC 6258
C. Parapsilosis
ATCC 22019
C. Lucitaniae
ATCC 200950
C. Glabrata
IP 35
C. Guilliermondii
clinical isolate
[42] Ficus drupacea Egypt Stem bark 7 isolated 7-7521µg/mL C. albicans • Isolate compounds show
compounds ATCC 26555 better antifungal activity than
and extract.
n-Hexane 4–15 µg/mL • Compounds 5-O-
extract methyllatifolin) and 7
(epilupeol acetate) exhibited
the highest antifungal
ctivety.
[43] Tamarix gallica Tunisia Leaves and ME 0.292 mg/mL C. parapsilosis, • Show antifungal activity.
flowers ATCC 22019 • Flower presence flavonoids
C. Albicans,
and leaves showed quercetin
ATCC 90026;
3-O-glucuronide these sug-
C. Krusei gest antifungal activity.
ATCC 6258;
C. Glabrata
ATCC 90030
44] Carissa opaca Pakistan Root ME ME: 20 mg/mL C. albicans ME showed moderate to high
Ethyl Acetate EA: 7.8 mg/mL ATCC 10231 antimicrobial activities and EA
(EA) displayed especially notable
efficacy.
[45] Helichrysum Italy - Essential oils 750 µg/mL C. albicans • Chitosan formulations in-
microphyllum (ESO) ATCC 10231 creased antifungal activity
subsp. Tyrrheni- against C. albicans.
cum
ESO with 94.5 µg/mL • Terpenes and alcohols such
Chitosan as c-curcumene and lina- ex-
amined is responsible for the
antifungal effect
[46] Rhaphiodon echi- Brazil Leaves Essential oils >1024 µg/mL C. albicans, X
nus (Nees and C. Krusei
Mart) C. Tropicalis
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[47] Carya illinoensis Brazil Leaves AE AE: 0.78 - 25 C. tropicalis • AE and EE were effective at
EE mg/mL ATCC 66029 all concentrations by inactiva-
EE:1.56 - 25 mg/mL C. parapsilosis ting germ tube production.
ATCC 22019
• Presence of phenolics acids
C. albicans
(gallic acid and ellagic acid),
ATCC 14053
flavonoids (rutin) and con-
densed tannin (catechin and
epicatechin).
[48] Buchenavia tetra- Brazil Leaves HE HE 156 - 2500 C. albicans strains ME showed the best activity
phylla CHL mg/mL F01, F02,F03,F08, which inhibit cell division and
EE CHL: 156-1250 F11,F14,F22,F23,F2 able enhance the action of flu-
ME mg/mL. 7,UFPEDA 1007 conazole
ME: 625-1250
mg/mL
EE :625-2500
mg/mL
[49] Corymbia inter- Australia Stem and leaves AQE 500 µg/mL, C. albicans • 80% AQEt of S. glomulifera
media was the most active.
Lophostemon 125 µg/mL • The leaves of S. glomulifera
suaveolens contain antibacterial compo-
nents: α-pinene, aromaden-
Syncarpia glomu- 31 µg/mL drene and globulol, eu-
lifera calyptin, and compounds be-
tulinic acid, oleanolic acid-3-
acetate and ursolic acid-3-
acetate
[50] Ocimum basilicum Italy - Essential oils 0.09 - 4.58 mg/mL C. albicans • T. vulgaris and O. vulgare
C. famata essential oils showed the best
Origanum vulgare 0.018 - 3.6 mg/mL activity against all the tested
Salvia sclarea No activity pathogens.
• Rich in monoterpenes, car-
Thymus vulgaris 0.09 – 1.87 mg/mL vacrol and thymol, there to-
Illicium verum 0.19 - >19.5 mg/mL gether can completely block
ergosterol synthesis and ma-
king porous the membrane
• S. sclarea showed no antifun-
gal effect
[51] Plumbago rosea India - Plumbagin 5 µg/mL C. albicans Show antifungal activity by
ATCC2091, disrupting biofilm.
C. tropicalis clinical
isolate
C. parapsilosis
clinical isolate
[52] Scabiosa arenaria Tunisia Flowers, fruits, BA 0.02 mg/mL C. ATCC reference • Show antifungal activity.
stems, leaves strains,
• Present of oleanolic acid and
and roots C. albicans
luteolin-7-O-glucoside show
ATCC 90028, good antimicrobial effect.
C. glabrata
ATCC 90030,
C. krusei
ATCC 6258,
C. parapsilosis
ATCC 22019.
[53] Bersama Ethiopia Leaves and EE 512 mg/mL C. albicans • 74% of the medicinal plant
abyssinica, roots extracts tested exhibited an-
Embelia schimperi, 512 mg/mL timicrobial effect against
Ocimum more of the 12 different mi-
lamiifolium, 512 mg/mL crobial strains.
R. steudneri
• E. schimperi, O. lamiifolium,
R. nepalensis 512 mg/mL
and R. steudneri was found to
Z. scabra 512 mg/mL
be the most promising plants
512 mg/mL
against microbes.
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[54] Euphorbia para- Tunisia Stems and CHL 0.015 – 5 mg/mL C. albicans Could be great potential as new
lias L leaves ATCC 90028 antimicrobial agents.
[55] Eucalyptus globu- Brazil Purchased Essential oil 0.219 mg/mL C. albicans • Nanoemulsion was more
lus (EO) C. tropicalis efficient for two of the three
C. glabrata C. species when compared to
Nanoemulsion 0.7 mg/mL free oil.
(NE)
• EO-NE protect the compo-
nents through nanoencapsula-
tion and increase of the con-
tact area due to the reduced
size of the nanoemulsion
may favor antibiofilm
activity.
[56] Cyclopia interme- South Purchased AQ 150 mg/mL C. albicans. ME show most effective against
dia Africa ME 7.5 mg/mL ATCC 10231; C. albicans
fermented AQ 150 mg/mL
57] Erythrina stricta India Stem bark DCM 7.8 mg/mL C. albicans. Both show significant antifungal
Roxb. EtOAc 125 mg/mL activity against C. albicans.
n-Hexane 125 mg/mL Present flavonoids and phenolics
[58] Matricaria recutita Egypt - Pharmacopeia 160 to 320 µg/mL. C. albicans • Combination of essential oil
(PhEur) grade ATCC 90028 with fluconazole and nystatin
essential oil showed synergic inhibitory
effects.
• Show the best when combi-
ning to tetracycline.
[59] Piper hispidum Brazil Leaves Crude extract 62.5 mg/mL C. albicans, Show antifungal activity against
C. parapsilosis C. albicans, by inhibition bio-
C. tropicalis. film formation. Presents antimi-
crobial properties of chalcones
[60] Justicia glauca USA Leaves Green synthe- 12.5 ± 0.3 (µg/mL ± C. albicans NPs greatly increased J. glauca
sis of gold SD) against C. albicans by interfe-
nanoparticals rence with growth-signaling
(AuNPs) pathway inside the cell via mo-
extract dulating tyrosine phosphoryla-
tion of growth essential peptides
substrate
[61] Funtumia africana South Leaves Isolated Methyl ursolate: 63- C. albicans • CHL show strongest syner-
Africa methyl ursola- µg/mL ATCC 10231 gistic activities with methyl
te HE:40 µg/mL ursolate low toxicity which
HE CH:80 µg/mL may support the use of this
CHL plant.
• Antimicrobial and anti-
inflammatory activities of the
crude extract provide some
support for the traditional use
of the plant.
[62] Pappea capensis South Leaves HE 0.39 - 0.78 mg/mL C. albicans Show antifungal activity
Africa. DCM
EtOAc
BA extracts
[63] Equisetum hye- Japan Stems Crude extract 6.5 - 52.4 mg/mL C. albicans Show antifungal activity and
male DCM C. kefyr negligible cytotoxicity. It con-
EtOAc C. geochares tains epicatechin and β-carotene-
C. krusei linoleic acid
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[64] Croton limae Brazil Leaves Essential oil >1024 (mg/mL) C. albicans • Show antifungal activity
ATCC 40006 against C. albicans, however
C. krusei antagonist effect was seen
ATCC 2538 when combine with benzoyl-
C. tropicalis metronidazole.
ATCC 40042
• Cedrol, eucalyptol, a-pinene,
b-pinene and linalool may be
responsible for the antibacte-
rial activity
[65] Citrus sinensis USA Peels Essential Oils 1.68 µg /mL C. albicans • Moderate activity
C. tropicalis • Can be used in oral hygiene
0.4 µg /mL C. glabrata products
Citrus latifolia C. guilliermondii,
C. lusitaniae, • Less toxic alternative to am-
photericin B.
[66] Haplophyllum Tunisia Leaves, Essential oils 0.30 mg/mL C. albicans • Effective and has potential to
tuberculatum stems ATCC 90028; prevent cancer development.
(Forssk.) A. Juss. C. glabrata
• Significant correlation existed
ATCC 90030;
between the concentrations of
C. parapsilosis
the essential oils.
ATCC 27853
C. krusei • Antifungal activity may be
ATCC 6258. attributed to R-(+)-limonene,
S-(−)-limonene and octanol.
[67] Camellia sinensis Brazil Leaves Green tea 16-33 µg/mL C. albicans • Antifungal activity was
(L.) O Kuntze ATCC 14053 highest in black tea> green
While tea 16-135 µg/mL C. albicans tea >white tea
Red tea >270 µg/mL ATCC 64548
• Suggesting no direct rela-
C. krusei
tionship with the concentra-
Black tea 16-33 µg/mL ATCC 6258
tion of total phenols.
[68] Leucaena leuco- Malaysia Leaves ME 3.15 - 25.0 mg/mL C. albicans • Significant antifungal activity
cephala C. tropicalis through inhibition of cell pro-
liferation and induced apop-
tosis in MCF-7.
• Contained condensed tannins
and phenols.
[69] Trametes hirsuta Serbia Dried mycelia EE 32.0 mg/mL C. albicans Showed low antifungal potential
Trametes gibbosa and fruiting BEOFB 811m in comparison with ketoconazo-
Trametes versico- bodies C. krusei le.
lor BEOFB 821m
C. parapsilosis
BEOFB 831m
[70] Artemisia Jordan Aerials Essential oils 1.25 mg/mL C. albicans Show antifungal and anti-
herba-alba ATCC 10231 inflammatory activities and
C. parapsilosis without detrimental effects.
ATCC 90018 Revealed an important inhibitory
C. tropicalis effect on germ tube formation
ATCC 13803
[71] Avicennia marina U.A.E. - EE - C. albicans L. inermis and P. oleracea
SC5314 showed significant anti-C. acti-
Fagonia indica - vity and against biofilm forma-
Lawsania inermis 10 µg/mL tion Lower cytotoxicity and
higher selectivity indices, both
Portulaca oleracea 10 µg/mL plant extracts represent promi-
sing area of future research.
Salvadora persica 25 µg/mL
Asphodelus -
tenuifolius
Ziziphus spina- -
Christi
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[72] Aster yomena Korea Aerial ME and ME: - C. albicans ME show no antifungal effect.
Isolated AP: 2.5 µg/mL ATCC 90028 Only isolated apigenin has the
compound antifungal activity.
apigenin (AP)
[73] Artemisia vulgaris Brazil Leaves Essential oils 100 µg /mL C. albicans All three are able to inhibit the
ATCC14057 growth of the C. genus yeasts.
Biden pilosa 64 µg /mL C. glabrata Differences in the contents of the
Sphagneticola 100 µg /mL ATCC2301 chemical components in the
trilobata C. krusei essential oils significantly in-
ATCC6258 fluence antifungal activity ac-
C. parapsilosis tion.
ATCC22018
[74] Muntingia cala- Philippi- Stem and dried EE Leaf: 0.625 mg/mL C. albicans Show antifungal activity. Pre-
bura L. nes leaf Stem: 2.5 mg/mL sence of sterols, flavonoids,
alkaloids, saponins, glycosides
and tannins
[75] Ixora megalophyl- Thailand Leaves Petroleum Leaf C. albicans EtOAc extract from the leaves
la stems ether (Pet), Pet:1250 mg/mL and the EtOAc and EE from the
EtOAc EtOAc:78 mg/mL stems possessed antifungal acti-
EtOH EtOH:156 mg/mL vities.
Stems
Pet:1250 mg/mL
EtOAc:78 mg/mL
EtOH:78 mg/mL
[76] Siegesbeckia China - EE, petroleum EE:2.50 µg/mL C. albicans EE showed the strongest antimi-
orientalis ether fraction PE-SO:4.0 µg/mL ATCC 1023 crobial, antioxidant and cytoto-
(PE-SO), EtOAc :1.25 µg/mL xic activities.
EtOAc, BA BA:2.50 µg/mL
and water WE-SO:2.50 µg/mL
fraction (WE-
SO).
[77] Berberis lycium India Roots Berbarine BE:41.6 ± 18.04 C. albicans Pure berberine found more ef-
Royle (BE), mg/mL SKUAST- TAM-1 fective than crude extract, fo-
ME ME: 187.5 ± 62.5 llowed by methanolic and
HE mg/mL aqueous extracts.
AQ HE: NA
AQ: 8 mg/mL
[78] Calamus leptospa- India Shoots Saponin 80 mg/mL C. albicans Significant amount of saponin
dix Griff. MTCC 3007 possesses antimicrobial proper-
ties.
[79] Sapindus sapona- India Trees Hydro alcoho- 390-1560 µg/mL C. albicans Show antifungal activity by
ria L. lic extract C. glabrata acting on cell membrane causing
C. tropicalis cell lysis within 60min.
C. parapsilosis
[80] Ziziphus nummu- India Leaves Zinc oxide >10mg/mL C. albicans ZnO NPs exhibited very good
laria nanoparticles ATCC2091 antifungal activity, even better
(ZnO NPs) NP: 1.25mg/mL C. glabrata than standard antibiotic Ampho-
and leaf NCIM3448 tericin B attributed to the small
extract size of synthesized ZnO NPs.
[81] Juniperus commu- Portugal Mature berries Essential oils 0.039-0.16 % C. albicans • Against all the tested organ-
nis ESAB. isms, support the use of tradi-
tional medication usage of
this species.
• Inhibited by morphological
changes in the cell mem-
brane. Also, antimicrobial
activity may due to monoter-
penes, such as terpinen-4-ol
and 1,8-cineol.
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[82] Artemisia judaica Jordan Aerial Essential oil 1.25 µg/mL C. albicans • Significantly inhibited germ
L. ATCC 10231 tube formation and disrupted
C. parapsilosis preformed biofilms of C. al-
ATCC 90018 bicans.
C. tropicalis
• It contains piperitone,
ATCC 13803
camphor and ethyl cinnamate
[83] Ipomoea procum- Brazil Leaves, Hydro- >250 µg/ /mL C. krusei X
bens stem and roots methanol C. parapsilosis
extracts C. albicans
[84] Brazil Leaves Essential oil 4,096 µg/mL. C. albicans • The oil caused the inhibition
C. krusei of C. albicans and C. tropica-
C. tropicalis lis by disrupting morphologi-
cal transition.
• Related to selena-1,3,7(11)-
trien-8-one and selina-1,3,
7(11)-trien-8-one epoxide,
[85] Cinnamomum Iran Leaves and Essential oils 125 to 175 mg/mL C. albicans Could be applied as supplemen-
verum bark C. Tropicalis tary agents along with conven-
C. Krusei tional antifungal drugs.
Caryophillium 700 to 1000 mg/mL C. Glabrata
aromaticus C. Parapsilosis
Artemisia dracun- 1000 to 2000 C. Famata.
culus mg/mL
Origanum vulgare 173 to 350 mg/mL
Cymbopogon 125 to 175 mg/mL
citratus
[86] Baccharis trinervis Brazil Aerial Essential oil X C. albicans, X
(Lam.) C. Parapsilosis
C. Tropicali
[87] Sedum sediforme Turkey - Petroleum PE:8 ± 0.4 µg/mL C. albicans • ME most active one.
ether (PE), AC:1 ± 0.2 µg/mL • Contains 4 phenolic acids
AC
ME:1±0.3 µg/mL (protocatechuic acid, p-
ME
coumaric acid, caffeic acid,
and chlorogenic acid and
flavonoids(quercetin)
[88] Mentha piperita Saudi Aerial Essential oil 1.50 ± 0.16 mg/mL C. albicans • Show significant antifungal
Arabia ATCC 26790 activity and potential to per-
form better an amphotericin
B.
• Presence of high menthol and
menthone components.
[89] Curcuma aerugi- Thailand - Essential oils 250 mg/mL C. albicans • Major components are
nosa Roxb ATCC 90028 oxygenated monoterpenes,
1,8- cineole and camphor
Curcuma glans K.
Larsen
Curcuma cf. xant-
horrhiza Roxb
[90] Thymus vulgaris Iran - ME 68 µg/mL C. albicans • C. Zeylanicum show better
ATCC10231 antifungal activity compared
Caryophillim 48 µg/mL to other.
aromaticus
• Antifungal activity may due
Echinophora 27 µg/mL to eugenol, cinnamic aldehy-
platyloba de, saponin, alkaloid and
flavonoid.
Allium cepa 75 µg/mL
Cinnamomum 18 µg/mL
zeylanicum
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[91] Cuminum cyminum Iran Seeds Alcoholic 578 mg/L C. albicans • Both show strong to moderate
extract ATCC 14053 activity.
Salvadora persica C. dubliniensis ATCC
• C. cyminum characterized by
4.9 mg/mL CD60, C. glabrata
high amounts of a-pinene, li-
ATCC 90030
monene and 1,8-cineole.
C. krusei
ATCC 6258
C. parapsilosis
ATCC 22019.
[92] Paeonia lactiflora USA Roots EE 49 mg/mL C. albicans Show antifungal activity associa-
SC5314 ted with cell membrane integrity
and permeability on (1.3)- β-D-
196 mg/mL C. albicans glucan synthase.
ATCC 18804
[93] Isodon flavidus China Twigs and Crude extract 62.5 mg/mL C. albicans. Show antifungal activity Fladin
(Hand. -Mazz.) leaves A and lophanic acid can break-
down the formed biofilm of
C. albicans.
[94] Rubus idaeus France Ripe and unripe n-hexane, > 1000 µg/mL C. albicans • HE and EtOAc have signifi-
fruits EtOAc C. glabrata cant anti-adhesion activity
BA C. parapsilosis. against C. albicans
• Contains high condensed
tannins.
[95] Pogostemon hey- India Leaves Patchouli 0.6-1 mg/mL C. albicans Inhibited the key virulent pro-
neanus essential oil ATCC-90028 perty of C. Albicans, the transi-
C. Glabrata tion from yeast cells towards
Cinnamomum 0.6 mg/mL MTCC 6507 hyphal formation of C. Albicans.
tamala C. Tropicalis
Camphor 1 mg/mL MTCC 310
[96] Pluchea dioscori- USA Leaf EE 30 mg/mL C. albicans strains Exhibited high antifungal activi-
dis ty which cause changes in
phospholipase, hemolysin, and
secreted aspartyl proteinase gene
expression could completely
collapse the yeast cell and inhibit
the growth.
[97] Equisetum tel- Iran Aerial Superfical SFE:32 mg/mL C. albicans • SFE method show more
mateia fluid extracti- MC&F: >128 appropriate for extraction
on (SFE), cold mg/mL against C. albicans.
maceration
• Antimicrobial attributed to
(CM) and
the phenolic substances iden-
Fractionation
tified such as catechin,
extracts (F)
kaempferol derivatives and p-
OH-benzoic acid.
[98] Pogostemon cablin India Purchased Patchouli PC: NA C. albicans • PH exhibited better antifungal
essential oil PH:25 mg/mL activities than the other two.
(PC, PH and PP:50 mg/mL
PP)
[99] Succisa pratensis Poland Leaves or ME 0.11 mg/mL C. albicans • Show antifungal activity.
flowers T. mentagrophytes
• The compounds 10-
(acetylmethyl) -(+), 3-carene,
methyl linolenate, hexadeca-
noic acid, pentacosane, hexa-
cosane, heptacosane and
thymol having strong antimi-
crobial activity.
[100] Tritomaria quin- China - Crude extract >128 mg/mL C. albicans wild Show antifungal activity
quedentata (Huds.) strain SC5314 and
four mutant strains
DSY448, DSY653,
DSY465, DSY654
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[101] Citrullus colocynt- Iran Fruits Hydroalcoho- 1.56 -12.5 mg/mL C. albicans Show antifungal activity
his lic extracts
[102] Salvia rhytidea Iran. - ME. 3.125 to > 100 C. albicans Show antifungal activity
Benth(Mint) mg/mL C. glabrata
C. tropicalis
C. krusei
C. parapsilosis
C. Lusitania
C. guilliermondii
[103] Allium hushidari, Iran - Essential oil 0.25- 2 mg/mL C. albicans • Show antifungal activity.
Allium sativum
• Antimicrobial activity is
related to alkaloids, tannins,
saponins, flavone and glyco-
sides.
[104] Laserpitium spp. Macedo- Roots and Extract 1.25 mg /mL C. krusei • Inhibition of biofilm.
nia rhizomes
• Major components are iso-
montanolide, laserpitine and
montanolide. All showed a
more pronounced effect than
fluconazole.
[105] Anthemis nobilis, Egypt Purchased Essential oils Fennel oil :0.78% C. albicans • Fennel essential oil had signi-
Foeniculum vulga- Others: NA ATCC 10231 ficantly higher antifungal ac-
re, C. Glabrata tivities compared with other
Simmondsia chi- tested.
nensis, C. tropicalis
Nigella sativa,
• Fennel essential oil alone or
Trigonella
in combination with flucona-
foenumgraecum,
zole could provide a promi-
Gadus morhua,
sing approach in management
Mentha piperita, of vulvovaginal candidiasis.
Syzygium aroma-
tic,
Zingiber officinale
[106] Cocos nucifera Brazil Purchased NaP 6.25 µg/mL C. albicans • Exhibited high antifungal
C. glabrata, activity against pathogenic
Candida spp.
• The nano-capsules formula-
tions prolonged storage, and
increased photostability of
clotrimazole and prolonged
drug release.
[107] Lycium barbarum Romania Leaves Phenolic oil 0.031-0.062 mg/mL C. albicans • Show antifungal activity.
ATCC 10231,
• The leaves contain higher
C. parapsilosis
amounts of chlorogenic acids
ATCC 22019
and flavonoid glycosides.
[108] Garcinia xantho- Brazil Fruits Xanthochy- 1 to 3 µg/mL C. albicans • Show antifungal activity and
chymus mol and can also potentiate the activi-
garcinol, ty of fluconazole.
isoprenylated • inhibited development of
benzopheno-
hyphae and subsequent bio-
nes
film maturation, inducing cell
death
[109] Spondias tuberosa Brazil Leaves HE 2.0 mg/mL C. albicans URM • Show antifungal activity by
5901, from ungual disrupting cell membrane.
scales
• It contains flavonoids,
hydrolysable tannins, sapo-
nins, terpenes and unsaturated
fatty acids
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[110] Holothuria scabra, Iran - Crude extract NA C. albicans X

Holothuria parva, ATCC 10231
Holothuria leucos-
pilota
[111] Glycyrrhiza glabra Spain Rhizomes and Phenolic >1.5 mg/mL C. glabrata, X
roots extract C. parapsilosis
C. albicans.
[112] Myracrodruon Brazil Bark EE 4-512 µg/mL (topi- C. albicans Show antifungal activity which
urundeuva cal) C. krusei contains flavonoids and tannins.
C. tropicalis
[113] Ficus elastica Cameroon Aerial roots ME 4.9 µg/mL; C. albicans ME show antifungal activity.
Roxb. ex Hornem. The most active antimicrobial
components are elastiquinone
and ficusosid
[114] Daucus virgatus Tunisia Aerial EtOAc 625 µg /mL C. albicans Exhibited moderate activity
(Poir.) Maire ME
[115] Pistacia vera L., Italy Hulls Essential oil 2.5-5 mg/mL C. albicans Show antifungal activity.
Bronte ATCC 64550
4 clinical strains of
C. albicans,
[116] Anisophyllea Guinea Pulp seed ME 500-1000 µg/mL C. albicans Both ethanol and methanol are
laurina R. Br. ex EE very effective to extract pheno-
lics and show antifungal activity.
[117] Thymus vulgaris, Poland Purchased Essential oils Cinnamon C. albicans and 76 • Cinnamon oil is the most
Citrus limonum, oil:0.002–0.125% isolates of C. glabra- active against C. albicans.
Pelargonium (v/v) ta
• All of the tested oils demons-
graveolens, Others: 0.005% or trated the ability to inhibit the
Cinnamomum less to 2.5% (v/v). transition of yeast to myce-
cassia,
lium form. Thyme, lemon,
Ocimum basilicum,
and clove oils affected cell
Eugenia caryop-
membranes by influencing
hyllus
potassium ion efflux, which
was not seen in the lemon oil.
• No synergistic interactions
between antifungal drugs;
possible synergism was bet-
ween amphotericin B and ge-
ranium oil.
[118] Lippia sidoides Brazil Purchased Essential oil 156 and 312 µg/mL C. albicans • Show antifungal activity
Cham ATCC 64548 against C. albicans
[119] Mentha piperita Brazil Purchased Essential oil 1.875 µg/mL C. albicans Show antifungal activity and
INCQS 40277 inactivate potentially spoilage
C. tropicalis yeasts in fruit juices through
ATCC 28707 disturbance of different physio-
logical functions in yeast cells.
[120] Hippophae rham- Poland Twigs and Extract 250 mg/mL (twig), C. albicans, Significant antifungal activity by
noides L leaves 31.5 mg/mL (leaf) ATCC 10231 fluco- inhibited morphogenesis such as
nazole-sensitive and germ tube and hyphae formation.
clinical,
C. glabrata G1
[121] Paeonia lactiflora Korea Root EE 196 µg/mL C. albicans, EE show good inhibitory effects
ATCC 188040 against biofilm formation by
C. albicans KCCM impeding cell adhesion and
50235 obstructing the morphological
transition of hyphae. Also inhib-
ited the cell wall synthesis and
damages cell membrane func-
tions which lead to cell swelling
and lysis.
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[122] Psidium guajava Brazil Leaves AQ and >8192 mg/mL C. albicans X

Hydroethano- C. tropicalis
lic extract
[123] Kedrostis africana South Dried tubers AcE Ac:0.312 mg/mL C. albicans • Show antifungal activity.
Africa AQ Aq: >5 mg/mL ATCC 10231
• The flavonoid, proanthocya-
EE Eth:0.325 mg/mL
nidin and total phenolic con-
centrations were higher in
AcE compared to the aqueous
and EE.
[124] Eucalyptus micro- Australia Leaves AQ 1250 µg/mL. C. albicans • Show antifungal activity and
corys ATCC 10231 was found to be a good sour-
ce of TPC, TFC, proant-
hocyanidins and saponins.
[125] Psiadia punctulata Saudi Leaves Extract 50 µg/mL C. albicans. • Show antifungal activity
(DC.) Vatke Arabia against C. albicans.
• Isolated 3′,4′,5,7-
tetramethoxyflavone, displa-
yed the ability to reduce bio-
film formation of C. albicans
by 90%
[126] Camellia sinensis Korea Seed Green tea seed 938 µg/mL C. albicans • Active compounds: theasapo-
(L.) O Kuntze extract ATCC 10231 nin E1, assamsaponin A and
assamsaponin B
• GTS extract can be used as a
safe and strong natural anti-
yeast.
[127] Psidium guajava, India Leaves Hydroethano- 8,192 µg/mL, C. albicans • Show antifungal activity
Psidium brownia- lic extracts C. tropicalis strains against C. albicans and are
num Mart. Ex DC effective on potentiating the
effect of fluconazole.
• Presence of phenols, flavo-
noids and tannins.
[128] Murraya koenigii India Leaves Hydro- 12.5-100 µg/mL C. albicans strain Show antifungal activity against
(L.) Spreng distillate MTCC 3017 C. albicans inhibited by the
essential oil compound mk309
[129] Melaleuca alterni- - - Essential oils 0.25-2% v/v C. albicans ATCC • All strains show antifungal
folia 10231, activity
C. glabrata,
Mentha piperita 0.03-0.25% v/v • Peppermint oil demonstrated
C. tropicalis,
the lowest antifungal activity.
Thymus vulgaris 0.25-2% v/v C. parapsilosis
C. krusei,
Syzygium aroma- 0.06-0.25 % v/v C. guilliermondii,
ticum C. lusitaniae,
C. dubliniensis,
[130] Combretum South Leaves AQ 1.25 mg/mL C. albicans • Antifungal activity followed
erythrophyllum Africa AcE by AQ > AcE >DCM> HE
DCM
• Provide some indication for
HE
the traditional use of the
plant.
[131] Strychnos spinosa Nigeria Leaves AcE 1.25 or >1.25 C. albicans Show antifungal activity and
Lam. ME mg/mL ATCC 10231 support the traditional use of this
DCM plant as treatment of infectious.
[132] Aloe trigonantha Ethiopia leaf latex Aloesin, 8-O- 400 µg/mL. C. albicans Show weak antifungal activity
L.C. Leach Methyl-7- ATCC 10231
hydroxyaloin
(Table 3) Contd….
Country MIC (mg/mL,

of Origin mg/mL)
[133] Nigella sativa India Leaves Hydro-steam 15.62 µg/mL C. albicans Ajwain and Black Cumin leaf
distilled 250 µg/mL MTCC-183, oils showed better antifungal
Murraya koienigii essential oils C. tropicalis activity by inhibition of cell
Trachiyspirum MTCC-184, membrane synthesis, specifically
ammi C. glabrata by extracting the sterols from the
MTCC-3019 membrane or inhibiting steroid
Piper betel synthesis.
[134] Carpolobia lutea Nigeria Leaves EE 25 mg/mL C. albicans • EE show significant antifun-
ME gal effect.
AQ
• Both AQ and HE show no
HE
inhibitory effect.
[135] Zuccagnia puncta- Argentina Aerial parts DCM 27.33-31µg/mL C. albicans • Show antifungal activity.
ta Cav. C. glabrata ZpE-LnE have synergistic ef-
fect, support the proper joint
Larrea nitida Cav. use of both antifungal herbs
in traditional medicine.
[136] Tetraglochin Argentina Leaves and Hydroalcoho- 12.5 and 25 µg/mL C. albicans • Show antifungal activity and
cristatum (Britton) aerial lic dry extract 144783, 134333, give support to their traditio-
Roth 2089; nal use for treating infections.
C. glabrata
• It contains hydrolysable and
031646, 042030, condensed tannins
031982;
C. tropicalis
1841;
[137] Satureja Khuzista- Iran Aerial EE 299.4 mg/mL C. albicans Show synergistic effect with
nica ATCC 10231 amphotericin B and ketoconazo-
C. albicans le, while this extract had no
ATCC 66506 a effect on clotrimazole activity.
[138] Alchemilla vulgar- Serbia Root ME >20 µg/mL C. albicans X
is L. ATCC 10259,
[139] Ferula assa- Iran oleo-gum-resin Essential oil 0.19 (0.12-0.25) C. albicans Show remarkable antifungal
foetida µg/mL CBS 5982, 1905 and activities
1949
[140] Thymus vulgaris Brazil Leaves Extracts 50 mg/mL C. albicans Show antifungal activity by
ATCC 18804, acting on the biofilm formation.
S. aureus It contains thymol, carvacrol,
ATCC 6538 linalool, geranoil, citral, tannins,
organic acids, flavonoids, mine-
rals.
[141] Eugenia leitonii, Brazil Leaves Dry extracts Barks: 15.62 ->2000 C. albicans The seeds of E. leitonii and the
Eugenia brasilien- pulps µg/mL ATCC 90028 seeds and leaves of E. brasilien-
sis, seeds E. leitonii (seed) sis were found to have strong
Eugenia myrciant- barks :15.62 µg/ mL) antifungal activity against C.
hes E.brasiliensis(leaf) albicans by acting on matu-
Eugenia involucra- :31.25 µg/ mL re biofilms. However, Bark
te E. brasiliensis show no antifungal effect.
(seed) :5.62 µg/ mL Phenolic compounds epicatechin
and gallic acid were the major
constituents in the extracts.
Abbreviations: *-: Not specified/Not available, *X: No antifungal effect.; *ME: Methanolic extract, * AC: Acetone extract, *AQ: Aqueous extract, *AQE: Aqueous ethanolic extract;
*EtOAc: Ethyl acetate extract, * EE: Ethanol extract, *Dichloromethane extract: DCM , *HE: Hexane extract, *CHL:Chloroform extract , *BA: butanol extract, *NaP: Nanoparti-
cles/Nano formulation.
The most common source types investigated were the membrane potential and permeability; disrupting transcrip-
aerial parts of the plants. Methanolic and ethanolic extraction, cell division and inhibition of virulence factors.
tions exhibited higher antifungal efficacy, amongst other
extracts. A total of 30 articles investigated the mechanisms Overall, the presented evidence shows that natural prod-
of the herbal extracts against C. albicans, which they exert ucts may be employed effectively as an alternative therapy
antifungal effects through inhibiting biofilm formation, hy- against C. albicans. Among the tested plants, common plants
phal transformation, germ tube inhibition; alteration of with a long history and well-known beneficial effects such as
Fig. (1). Flowchart of search strategy and study selection procedure. (A higher resolution/colour version of this figure is available in the elec-
tronic copy of the article).
tea (C. sinensis), tea tree oil (M. alternifolia), cinnamon (C. 3.2. Herbal Interventions In Vivo
verum), cumin (C. cyminum), henna (L. inermis), mint (M.
When investigating the in vivo effects of herbal extracts
piperita), and thyme (T. vulgaris), whose antifungal activity on C. albicans, 9 articles that matched the search criteria
was confirmed in several studies of this review, support the with a total of 11 plants were examined (Table 2). Most stud-
traditional use of these plants. Furthermore, several novel ies used rats as the host organism by infecting them with C.
natural herbs have been discovered as potential adjunctive albicans in which, only Vicia faba and Morinda tomentosa
treatments against C. albicans. show no antifungal activity against C. albicans [12, 14]. The
Fig. (2). Distribution of the geographical locations of the origins of plants cited in this review, per source country. (A higher resolu-
tion/colour version of this figure is available in the electronic copy of the article).
most active plants were C. sinensis with MIC values of 40 herbal extracts with antifungal drugs in which, M. alternifo-
µg/mL [13]. Topical applications of 4% L. innermis show lia, Buchenavia tetraphylla, Foeniculum vulgare, G. xantho-
similar or better effect than clotrimazole and Mitracarpus chymus, P. guajava, Psidium brownianum Mart. ex DC and
frigidus presents antifungal activities greater than flucona- Satureja khuzistanica showed a synergistic effect with flu-
zole against candidiasis [11, 16]. M. alternifolia inhibited conazole. Matricaria recutita showed an additive effect with
biofilm formation [15] Syzygium cumini and Jatropha cur- nystatin and fluconazole. P. graveolens showed synergism
cas, which contained a high amount of phenols and flavo- with amphotericin B. S. khuzistanica potentiated the effect of
noids are responsible for the inhibitory effect against C. albi- amphotericin B and ketoconazole. However, five tested ex-
cans [17, 19]. Nano-formulations of the seeds of S. cumini tracts, which are T. vulgaris, Citrus limonum, Cinnamomum
exhibited an improved antioxidant activity of the plant ex- cassia, Ocimum basilicum and Eugenia caryophyllu showed
tract as compared to other formulations [17]. When compar- little or no enhancement. The antagonist effect of Croton
ing all the in vivo herbal interventions, L. innermis and M. limae with benzoyl metronidazole was observed.
alternifolia seem to have the most significant antifungal ac-
Three herbal interventions demonstrated greater antifun-
tivity with the MIC values as low as 5-10 mg/mL in vivo and
gal effect than common antifungal drugs in which, Z. num-
CFU value 5.33 Log10 [10, 15]. Nano formulations of all sev-
mularia presented better antifungal activities over Ampho-
en herbal extracts that were included in this review (P. graveo-
lens, Eucalyptus globulus, Justicia glauca, Ziziphus nummu- tericin B, due to the incorporations of synthesized zinc nano-
particles that help to enhance plant properties [80]. The pres-
laria, Pogostemon cablin and Cocos nucifera) demonstrated
ence of isomontanolide, leserpitine and montanolide in La-
increasing plants properties and better antifungal effects than
serpitium species exhibited a more pronounced effect than
traditional extraction methods (Tables 2 and 3).
fluconazole by inhibiting the hyphae and subsequent biofilm
maturation [104]. In a study of the aerial parts of M. piperita,
3.3. Herbal Interventions In Vitro
the MIC value of the extracts (1.5 µg/mL) [88] was smaller
Table 3 summarizes the herbal interventions in vitro, than the Amphotericin B (MIC: 5 µg/mL), implying that it
where 122 studies were included explaining the effects of has the potential to perform better antifungal activities than
175 herbal interventions [20-141]. Most of the herbal ex- the synthetic drugs.
tracts examined demonstrate activities against C. albicans in
which, the most active were C. sinensis, Citrus sinensis, Cit- 3.4. Preparation of Herbal Extracts
rus latifolia, C. nucifera, Ficus elastica Roxb. Ex Hornem,
M. piperita , Garcinia xanthochymus, M. alternifolia, P. Differences in parts of plants extracted and extraction
graveolens, Siegesbeckia orientalis, Sedum sediforme and L. methods on the same plant greatly influenced its antifungal
inermis with MIC values ranging from 0.0945 µg/mL to 10 activities. In the study of Piper guineense, the fruits and leaves
µg/mL. A total of 25 natural extracts were ineffective against were prepared in five different extracts. Among these, aqueous
C. albicans. Twelve articles assessed the synergistic effect of extraction shows no inhibitory effect, while methanolic
Fig. (3). Chemical structures of (a) Catechins, (b) Gallic acid, (c) Thymol, and (d) condensed Tannins, as described in the systematic review.
extracts present the most significant activity with MIC of 39 through nanoencapsulation and increase the contact area due
µg/mL and the rest with MIC of 78 µg/mL [24]. In another to the reduced size of the formulations, which improves anti-
study investigating Leguminosae family species, the authors biofilm activity. In the study of J. glauca against C. albicans,
examined the leaves of 8 plants which were prepared in both the nanoparticles greatly inhibited bacterial growth by inter-
methanolic and ethanolic extracts, showing that Withania fering with the growth-signaling pathway inside the cell via
somnifera, Echinophora platybola and Zingiber officinale modulating tyrosine phosphorylation of growth essential
demonstrated better effect in ethanolic extracts, while Cur- peptides substrate [60]. In addition, in the study of C. nucif-
cuma longa and Pogostemon parviflorus present better effect era, the nano-capsule formulations exhibit favourable prop-
in methanolic extracts [28]. Another study, using hexane and erties after 60 days of storage and in prolonged drug release
chloroform extracts of the leaves of B. tetraphylla, exhibited [106].
significantly greater inhibition as compared to ethanolic and
Several studies have examined the significant antifungal
methanolic extracts [48]. It appears that it is difficult to gen-
effects of these herbs more than once, which are S. persica,
eralise and select an extraction method that preserves the
C. sinensis, C. verum, E. uniflora, L. inermis, M. alternifolia,
greatest activity of the plant extract that is valid for all
M. piperita, P. lactiflora, P. graveolens, S. cumini and T.
plants. It is equally difficult, given the range of plant types
and parts used in the studies, to generalise about the specific vulgaris. Two studies [71, 91] revealed that S. persica (MIC:
25 µg/mL and 4.8mg/mL) had strong to moderate activity
part of a plant, which would give the highest concentration
against different pathogenic Candida species. Both use the
of the active substance. It can, therefore, be concluded that
alcoholic extraction methods and the results are in accord-
the extraction method and selection of the part of the plant to
ance with each other.
be used must be individualised on a plant-by-plant basis.
Three studies demonstrated the activity of C. sinensis [13,
However, when comparing common extraction methods
such as methanol and aqueous extracts with nano-formulated 58, 118] in which, the leaf extracts (MICs ranging from 16-
135 µg/mL) exhibited higher antifungal activities than the
extracts, the use of nanotechnology greatly improves the
seeds (MIC: 938 µg/mL). Also, studies revealed that green
plant’s properties and the antifungal effects remain active for
and black leaves present better activities than white and red
a longer period of time. The increase in antifungal activity
tea leaves, which may be due to different fermentation meth-
may be attributed to its small size (200nm), which may acti-
ods. What’s more, a higher percentage of catechins are found
vate the passive transport mechanism across the cell mem-
brane. The study of P. graveolens, revealed that nano- in green tea leaves, which are well known for their antioxi-
dant activity. Catechins are reducing agents or chelating
formulations of geranium oil (MIC: 1.82 µg/mL) are twice as
metal ions, which are able to inhibit both DNA damage and
active as crude extracts (MIC: 3.64 µg/mL) and the former
lipid peroxidation, ultimately cause membrane integrity
are sufficiently active to reduce the amount of biofilm on
[142]. The final study showed that C. sinensis was effective
catheters [117]. The nanoparticles protect the components
both in vivo and in vitro against C. albicans [13]. All three tivity in 11 herbal extracts [18, 31, 47, 75, 95, 104, 109, 113,
studies demonstrate a significant effect of tea tree against C. 128, 136, 140].
albicans.
Saponins are phytochemicals, which can be found most
When comparing two studies using cinnamon [37], the in peas, soybeans and herbs. In this review, multiple studies
aerial parts of the plant with the MIC values of 31.25 to 62.5 reveal the potential antifungal activities against C. albicans
µg/mL exhibited greater fungicidal effects than the leaves in the presence of saponins [40, 41, 75, 79, 80, 91, 104, 110,
and bark (MIC: 127-175 µg/mL) [95]. Both studies revealed 125, 127]. However, in this review, the detailed mechanisms
the importance of cinnamaldehyde and cinnamaldehyde di- of action of saponins have not been well investigated. Pre-
methyl-acetate against microorganisms. In other studies, all vious research demonstrated that saponin is able to interfere
five studies investigating T. vulgaris exhibited significant with sterols, leading to inhibition of yeast-hyphal transition
antifungal activities of this plant against C. albicans [50, 91, and biofilm formations [144].
118, 129, 140]. The results demonstrated the importance of
Flavonoids are metabolites widely present in most vege-
thymol as an active agent inhibiting biofilm formation, pro-
tables, particularly green and red vegetables. Traditional and
moting high cell viability, having anti-inflammatory effects
local communities used these plants due to their anti-
and presenting no genotoxicity [140].
inflammatory, antioxidant, anti-depressant and anti-infective
effects. The mechanism of action has not been elucidated
3.5. Active Compounds
completely, even though it is believed to interfere with the
Phenolic compounds have been studied extensively of cell wall and/or the ergosterol synthesis [145]. In this present
their wide range of antioxidants and beneficial effects on the review, several articles exhibited the importance of flavo-
human body for decades. In this systematic review, numer- noids in against microorganisms [17, 19, 21, 31, 40, 43, 47,
ous active compounds have been identified to be active 58, 75, 88, 91, 108, 110, 113, 124, 128, 140]. In the study of
against C. albicans. Compounds that stand out for their S. cumini, stating that plants containing high flavonoids were
marked antifungal activity include phenols such as gallic found to have strong inhibitory effects on the formation and
acid, thymol, and flavonoids (especially catechin – Fig. 3a), metabolic activity of C. albicans biofilms or planktonic cells
polyphenols such as tannins, terpenoids and saponins. [40]. Catechin is a flavan-3-ol type natural phenol commonly
found in oolong and green tea. Its anti-oxidant, anti-
Gallic acid is a trihydroxybenzoic acid with antioxidant, hypertensive, anti-inflammatory, anti-proliferative, anti-
anti-inflammatory, and antimicrobial properties (Fig. 3b). In thrombogenic, and anti-hyperlipidemic activities have been
this review, four articles reveal the antifungal effectiveness clearly illustrated through various in vitro and in vivo stud-
of gallic acid [17, 31, 46, 141]. Particularly in the study of ies. It was found that catechin can induce the generation of
Cochlospermum regium, it has been demonstrated that the reactive oxygen species (ROS). ROS are implicated in the
antifungal mechanism of gallic acid is either by binding to disruption of molecular mechanisms such as angiogenesis,
ergosterol on the cell membrane that leads to pore formation extracellular matrix degradation and have been shown to
or by distrusting the enzymes responsible for the ergosterol lead to cell apoptosis [146]. The antifungal effect of cate-
synthesized, thereby causing membrane damage [32]. chins is demonstrated across several of the articles included
Thymol (2-isopropyl-5-methylphenol) isomeric with car- in this review, all supporting the role played by catechin as
vacrol (Fig. 3c) is the main monoterpene phenol isolated an antifungal against C. albicans [47,68,98,141]. In addition
from plants belonging to the Lamiaceae, Verbenaceae, to catechin, green tea seeds extract contain theasaponin E1,
Scrophulariaceae, Ranunculaceae, and Apiaceae families. It assamsaponin A and assamsaponin B, all of which were ac-
has been used for treatment due to its antioxidant, anti- tive against C. albicans and may have applications in food
inflammatory, local anaesthetic, antinociceptive, antiseptic, preservation against yeast contamination [127].
antibacterial, and antifungal effects as well as for their bene- Terpenoids, sometimes called isoprenoids, can be found
ficial effects on the cardiovascular system [143]. The studies in the leguminous plant, turmeric and mustard seed. In this
of T. vulgaris and Succisa pratensi revealed that thymol is review, a number of investigations report that plant extracts
able to block ergosterol synthesis and ultimately caused pore like Helichrysum and Juniperus communis containing terpe-
formation in the membrane [49,99]. noids exhibited antifungal activity against C. albicans [22,
Tannins (Fig. 3d) are known for their potent antioxidant, 31, 45, 82, 90, 110]. The proposed mechanism of action is
cytotoxic and antimicrobial activities. The study of Ricinus that terpenoids have a fungistatic effect on Candida by mod-
communis suggests that the potential fungicidal activity oc- ulating specific signaling pathways (TOR pathway or calci-
curs by the targeting of surface-exposed adhesins, cell wall um signalling), rather than by creating nonspecific mem-
polypeptides and membrane-bound enzymes of the fungal brane lesions. The result of this is the alteration of gene
cell. The proposed mechanism involves complex formation transcription and stasis [147].
between tannins and flavonoids with nucleophilic amino Other similar active compounds have been identified,
acids in proteins, leading to the inactivation of the proteins such as g-terpinene and 1,8-cineole in Lavandula binaluden-
and loss of function. The methanolic extracts show greater sis and C. cyminum [37,91]; 5-O-methyllatifolin; epilupeol
antifungal effective over aqueous and ethanolic extracts, due acetate in Ficus drupacea L. [42]; α-pinene, aromadendrene,
to the higher preservation of the tannins, flavonoids and ter- globulol, betulinic acid, oleanolic acid-3-acetate and ursolic
penoid compounds in the extracts. In this systematic review, acid-3-acetate present in S. glomulifera, C. cyminum and S.
tannins were found to be present and showed antifungal ac- persica [49]; a-pinene, limonene and 1,8-cineole, oleanolic
acid and luteolin-7-O-glucoside in Haplophyllum tubercula- postulated that a longer period of treatment and higher con-
tum (Forssk.) A. Juss. [66]; vepicatechin and β-carotene- centrations could lead to an overestimation of positive out-
linoleic acid in Equisetum hyemale [63]; and selena- comes.
1,3,7(11)-trien-8-one in E. uniflora [63]. Further studies are
required in order to characterize their antifungal activity The parts of the plants collected are also different such as
against C. albicans, since their mechanisms of action are not bark, roots, leaves, flowers, hulls and seeds. A difference in
yet well established. concentrations used between in vivo and in vitro studies
could lead to variation in response mechanisms towards the
extracts. One drawback relates to this review is that majority
2.6. Strengths
of the studies were the very first study of examining the ac-
Only clinical studies, clinical trials and RCTs are includ- tivity of the extracts or in the early phase of trials. Several
ed in this systematic review in order to reduce experimental studies did not illustrate the antifungal mechanisms and ac-
bias. Most trials used placebos or standard antifungal agents tive components. Another concern is that the safety measure
in the control group. Overall, the majority of herbal interven- of the studies and their potential interactions with other
tions reviewed indicate the antifungal effect and the major drugs were not investigated. Further studies are needed to
bioactive compounds responsible for the antifungal activity ensure the effectiveness, determine the mechanisms of action
against C. albicans. as well as efficacy, safety and intrinsic toxicity of the active
compounds in vivo. During the data collection process, only
2.7. Limitations English studies are included; therefore, language bias could
be another restriction of this study.
This systematic review highlights the lack of consensus
and standardization of MIC values defining the strength of
CONCLUSION
antifungal activity specifically for C. albicans. Each investi-
gator and study determine its own scale regarding what is The results show that a wide range of plant extracts are
significant inhibition and what is not. For example, the stud- able to inhibit C. albicans in vitro. The most active extracts
ies of Glycyrrhiza glabra (MIC:1500 µg/mL) and Rhaphio- were M. alternifolia, Cit. sinensis, C. latifolia, C. nucifera,
don echinus (MIC:1024 µg/mL) are reported inactive [111, F. elastica Roxb. Ex Hornem, M. piperita, G. xanthochymus,
46], on the contrary, in the case of M. tomentosa with MIC P. graveolens, Sedum sediforme, L. inermis and S. orientalis.
value as low as >32 µg/mL is considered ineffective by the The least active extracts were R. echinus, and G. glabra. The
investigator [14]. However, in general, most authors consid- most active extract in vivo was C. sinensis.
ered MIC values below 100 µg/mL as significant; between
The most common source types investigated were the
100-1000 µg/mL as moderate; and above 1000 µg/mL as
aerial parts. Most plants with methanolic and ethanolic ex-
inactive.
traction exhibited high antifungal efficacy, amongst others.
The majority of studies utilized methanolic and ethanolic This could be due to the increased solubility of non-polar
extracts, whereas other extraction methods such as aqueous, compounds in such solvents [151]. The most crucial compo-
hexane, ethyl-acetate, acetone and dichloromethane. Other nents that have proved to have antifungal activities were the
formulations studies used essential oils. Some drawbacks of phenols such as gallic acid, thymol, and flavonoids (especial-
essential oils have been identified, such as chemical com- ly catechin), polyphenols such as tannins and terpenoids. The
plexity, high volatility, susceptibility to degradation and oxi- incorporation of nanotechnology shows promising results in
dation, insolubility in aqueous systems and low bioavailabil- the use of natural compounds against bacterial infections.
ity [148]. These characteristics hinder their direct use of
products, although all studies established the extraction pro- LIST OF ABBREVIATIONS
cess and methods thoroughly and in detail. Several factors,
like temperature, pH, particle size and solvent, may affect DNA = Deoxyribonucleic acid
the outcomes. RNA = Ribonucleic acid
Furthermore, the difference in concentrations, quantities, BCE = Before Common Era
incubation time and treatment duration are not equivalent,
which will greatly influence the outcomes and make it diffi- CFU = Colony Forming Units
cult to compare. Most of the in vitro studies are incubated MIC = Minimum Inhibitory Concentration
mostly for 24 hours; however, in some studies, it may extend
to 48 to 72 hours, allowing the formation of the biofilm. The TTO = Tea Tree Oil
incubation temperatures range from 30-37ºC, and a variety PRISMA = Preferred Reporting Items for Systematic Re-
of culture methods are used across the studies, for example, views and Meta-Analyses
agar, microwell, and sabouraud dextrose agar plates. As for
the treatment duration, in vivo studies using C. sinensis and CONSENT FOR PUBLICATION
M. alternifolia, the mice were treated for 5 days, whereas, in
the study using S. cumini, the rats were treated for 21 days Not applicable.
[13, 15]; and the treatment period was 2 weeks in the study
of Astragalus membranaceus [18]. Several herbal and ex- FUNDING
traction solvent concentrations were used in which it can be None.
CONFLICT OF INTEREST http://dx.doi.org/10.1016/j.phytochem.2014.06.004 PMID:

24984572
The authors declare no conflict of interest, financial or [15] de Campos Rasteiro, M.M.; da Costa, A.C.; Araújo, C.F.; de Ba-
otherwise. rros, P.P.; Rossoni, R.D. Essential oil of Melaleuca alternifolia for
the treatment of oral candidiasis induced in an immunosuppressed
mouse model. BMC Complement. Altern. Med., 2014, 14, 489.
ACKNOWLEDGEMENTS http://dx.doi.org/10.1186/1472-6882-14-489 PMID: 25510285
[16] Campos, L.M.; de Melo, L.; Lemos, A.S.O.; Guedes, M.C.M.R.;
Declared none. Silva, T.P.; Figueiredo, G.F.; Reis, J.L.; Rocha, V.N.; Melo,
R.C.N.; Araújo, M.G.F.; Apolônio, A.C.M.; Scio, E.; Fabri, R.L.
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Herbal Extracts with Antifungal Activity against Candida albicans: A Sys-

Hsuan Hsu1, Chirag C. Sheth2 and Veronica Veses3,*

1. INTRODUCTION Candida tropicalis, Candida parapsilosis, and Candida

1389-5575/20 $65.00+.00 © 2020 Bentham Science Publishers

Table 1. List of inclusion and exclusion criteria.

Inclusion Criteria Exclusion Criteria

C. albicans strains must be tested Algae/Animal/Insects as interventions.

Results must include antifungal assessment/evaluation method using MIC in vitro

Full length article available -

Published between Jan 1,2015 to Feb 23rd, 2019 -

[14] Morinda tomentosa Indonesia Roots ME >32mg/mL - Galleria C. albicans x

Country MIC (mg/mL,

Country MIC (mg/mL,

Country MIC (mg/mL,

Echinophora EE: 2.3 mg/mL

Country MIC (mg/mL,

Country MIC (mg/mL,

Country MIC (mg/mL,

Country MIC (mg/mL,

Country MIC (mg/mL,

Country MIC (mg/mL,

Country MIC (mg/mL,

Country MIC (mg/mL,

[110] Holothuria scabra, Iran - Crude extract NA C. albicans X

Country MIC (mg/mL,

[122] Psidium guajava Brazil Leaves AQ and >8192 mg/mL C. albicans X

Country MIC (mg/mL,

CONFLICT OF INTEREST http://dx.doi.org/10.1016/j.phytochem.2014.06.004 PMID:

delivery of clotrimazole. Colloids Surf. B Biointerfaces, 2014, 116, http://dx.doi.org/10.1016/j.indcrop.2018.10.064

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