Saudi Journal of Biological Sciences 27 (2020) 142–146

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Saudi Journal of Biological Sciences

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Original article

The beneficial effect of Indonesian propolis wax from Tetragonula sp. as a

therapy in limited vaginal candidiasis patients
Siti Farida a,b,d,⇑, Muhamad Sahlan c,d, Etin Rohmatin e, Robiatul Adawiyah d,f,g
a
Department of Medical Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
b
Drug Development Cluster, Indonesia Medical Education and Research Institute, Universitas Indonesia, Jakarta, Indonesia
c
Department of Chemical Engineering, Faculty of Engineering, Universitas Indonesia, Jakarta, Indonesia
d
Research Centre for Biomedical Engineering, Faculty of Engineering, Universitas Indonesia, UI Depok, Indonesia
e
Department of Health Polytechnic Republic of Indonesia’s Health Ministry Tasikmalaya, West Java, Indonesia
f
Parasitology Department, Faculty of Medicine, Universitas Indonesia, Campus UI Salemba, Jakarta, Indonesia
g
Parasitology Clinical Program, Faculty of Medicine, Universitas Indonesia, Indonesia

a r t i c l e i n f o a b s t r a c t

Article history: Vaginal candidiasis characterized by abnormal vaginal discharge and itching usually treated by azole’s
Received 1 May 2019 drug or nystatin; however, some results of treatment are unsatisfied and become recurrent. Propolis con-
Revised 6 June 2019 taining polyphenols and flavonoids is known to have anti-inflammatory and antimicrobial activity. This
Accepted 14 June 2019
study investigated the effect of Indonesian propolis wax from Tetragonula sp. as a therapy in limited vagi-
Available online 15 June 2019
nal candidiasis patients. The subjects were women who came to the Tasik Community Health Centre met
the inclusion criteria such as clinical complaint and laboratory evaluation (positive hyphae/pseudohy-
Keywords:
phae and culture on Sabouraud Dextrose Agar (SDA) medium) from a vaginal swab. Evaluation of anti-
Ovule
Propolis wax
candida effect of propolis was determined by clinical remission and the absence of Candida’s growth
Vaginal candidiasis on SDA medium. Forty subjects were randomly assigned to those receiving treatment by ovule propolis
Vaginal discharge (n = 20) and that treatment by nystatin (n = 20) as a control, once daily, for seven days, respectively. All
methods have been approved by the Ethics Commission of the Faculty of Medicine, Universitas Indonesia.
Our results indicated no significant difference in the laboratory evaluation of patients who have treated
ovule propolis compared to standard therapy. This study suggests that propolis wax has a beneficial effect
to develop as an anti-candida agent for vaginal candidiasis therapy.
Ó 2019 Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access
article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction symptom of an infection of genital organs such as vulvitis, vagini-

tis, cervicitis, and pelvic inflammatory disease. The characteristics
One of the reproductive health concern in women that need to of abnormal (pathological) vaginal discharge include a change of
be observed is reproductive tract infections frequent characterized color, unpleasant odors, and related symptoms such as itching,
by abnormal vaginal discharge. In women, vaginal discharge can burning, or pain during sexual intercourse (Bitew and Abebaw,
arise physiologically due to hormonal or pathological influences 2018). In Indonesia, about 90% of women have the potential to
caused by infection by bacteria or fungi (Mitchell, 2004). Abnormal experience vaginal discharge caused by fungal infection because
(pathological) vaginal discharge is a vulnerable problem for Indonesia is a tropical country, so the fungus is easy to grow
women because it can cause psychological disturbance or as a (Nurul and Qomariyah, 2001). Also, 75% of women are thought at
least once suffered from vaginal candidiasis (Mitchell, 2004). Can-
⇑ Corresponding author at: Department of Medical Pharmacy, Faculty of dida albicans was the most common cause of vaginal candidiasis
Medicine, Universitas Indonesia, Jakarta, Indonesia. (Sobel et al., 2004; Sobel, 2016).
E-mail address: [email protected] (S. Farida). C. albicans is classified as a normal flora colonized in mucosal
Peer review under responsibility of King Saud University. tissue (oral, vaginal and gatrointestinal), nail and skin, where cir-
cumstances changes allow C. albicans transition from yeast-like
to hyphal morphologies growth leads to cause candidal infection
(Haghdoost et al., 2016). Risk factors that can increase the inci-
Production and hosting by Elsevier dence of C. albicans infection include inadequate immune system,

https://doi.org/10.1016/j.sjbs.2019.06.010
1319-562X/Ó 2019 Production and hosting by Elsevier B.V. on behalf of King Saud University.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 S. Farida et al. / Saudi Journal of Biological Sciences 27 (2020) 142–146 143

hormone imbalance, pregnancy, and poor personal hygiene. In gen- 2.1. Ovule preparations
eral, the treatment of candidiasis infection is treated by Azole med-
ication which works by inhibiting the ergosterol biosynthesis Propolis wax ectract 5% from Tetragonula sp. as an active ingre-
required in the generation of C. albicans cell membrane. Nowadays, dient was mixed with Oleum Cacao and other added ingredients
however, it has been found that some of the Candida species caused that have been melted on a hot plate 60 °C. The mixture was then
vaginal candidiasis are becoming resistant to the Azole group (Dota poured into the ovule mold. After 15 min left at room temperature,
et al., 2011; Lemos, 2009) that influenced by the chemical compo- the ovules were put into the refrigerator 4 °C for 2 h. Then, the
sition of biofilm matrix of Candida species (Al-Fattani and Douglas, ovule propolis was removed from the refrigerator and put at room
2006; Uppuluri et al., 2009). Therefore, it is necessary to find an temperature for 30 min. Furthermore, ovula propolis was then
effective alternative drug for the treatment of vaginal candidiasis. removed from the mold and packaged into aluminum foil which
Propolis is a sap (resin) substance produced/secreted by leaf has been sprayed with alcohol before. The methods of the ovule
buds and also the stem part, which seeps out through the skin of preparations used are the result of the previous study from the
plants collected by bees and mixed with beeswax and wax. Bees research team who has obtained the patent of Intellectual Property
use propolis not only as a nest-building material but also as a Rights.
means of maintaining low levels of bacterial and fungal concentra-
tions in bee hives. Propolis is a bioactive compound in a honey- 2.2. Wet examination of samples
comb containing polyphenols, terpenes and flavonoids (Bankova
et al., 2004, 2014, that have anti-inflammatory, antimicrobial, We collected a vaginal secret using a sterile swab. Then a sterile
antioxidant and antiviral activities (Lotfy, 2006, Farnesi, 2009, swab was inserted into a sterile tube contained 0.9% sterile saline
Cardoso et al., 2010, Kim et al., 2011, Ordonez et al., 2011, fluid. After mixing, the swab containing the sample was applied
Trusheva et al., 2011, Bittencourt et al., 2015, Nina et al., 2016). to the sterile object glass until the sample was shed and then cov-
These compound make propolis have potential anti-fungal therapy. ered with a glass lid. Furthermore, the sample was examined under
Furthermore, an in vitro study conducted by Siqueira et al. (2015), a microscope with a 40 magnification. Positive Candida sp. was
showed that the anti-fungal ability of red propolis against most determined by finding the hyphae/pseudohyphae.
samples of Candida sp. In utilization, propolis obtained must be
purified before further processing. The by-product of the propolis
2.3. Culture examination of samples
purification process is the propolis wax which has so far not been
utilized further because the polyphenolic content in the propolis
The sterile sample from vaginal swab was inserted into a sterile
wax is less than that of pure propolis. However, in such a small
tube contained 0.9% sterile physiological fluid. To identify the spe-
amount, polyphenols in wax propolis were proven to be effective
cies of Candida, all samples were then inoculated onto to culture
in inhibiting C. albicans’ growth reaching 76% in concentrations of
medium, Sabouraud Dextrose Agar (SDA) medium and chro-
79.43 mg/ml (Hudnall, 2007). Furthermore, (Velikova et al., 2000)
mogenic agar medium parallel, respectively. Inoculation on SDA
reported that Brazilian propolis from native stingless bee had
and the chromogenic medium was carried out in Biosafety cabinets
antibacterial effect.
(BSC) II. SDA medium does not need to be wrapped in anything,
Based on the location of the formation, propolis is distinguished
while the chromogenic medium must be package in aluminum foil
over two types, i.e., fine propolis (inside honeycomb) and rough
to avoid light. Furthermore, the samples were then incubated at
propolis (outside of the honeycomb). The compounds of rough
room temperature for SDA medium and to be at 37 °C for chro-
and fine propolis may be different which will have an impact on
mogenic media. Chromogenic medium readings were carried out
the activity of each. Antifungal activity possessed by propolis can
over 48 h while in SDA medium after 72–120 h. Positive of Can-
be used to treat abnormal vaginal discharge.
dida’s growth was determined by the presence of more than 10
This study examined the beneficial effect of the innovation drug
Candida colonies on SDA medium.
containing an effective type and concentration of propolis wax
material could inhibit Candida sp growth as a treatment of vaginal
candidiasis. The novelty of this study is selecting the kind of propo- 3. Results and discussion
lis among fine propolis, rough or fine-rough mixtures based on
their chemical compounds and sufficient concentrations that can Drug preparations in the form of vaginal suppositories (ovules)
inhibit the growth of C. albicans in ovule preparations. was selected because the propolis as an active ingredient can
directly reach the vagina as the target area for treatment to be fas-
ter and more effective. Ovule propolis with dimension size
2. Material and methods 3  1.1  1.1 cm and its specific form are suitable for adult women
(Fig. 1). Compared to using swab of water soluble propolis in vagi-
The research design was a study of the benefits of propolis wax nal track, ovule propolis preparation is easier to use by themselves
implemented to a limited number of vaginal candidiasis patients. and propolis get longer contact with vaginal mucosa. Moreover,
The wax propolis was extracted from Tetragonula sp. propolis from the administration before sleep at night make propolis was kept
Sulawesi island. The research subjects were women who came to in vaginal tract around 6 h and it can be more effective to control
the Tasik Community Health Centre with complained about abnor- candidiasis. Furthermore, the vaginal wall is very well suited for
mal vaginal discharge and itching which fulfilled the inclusion cri- the absorption of drugs, since it contains a vast network of blood
teria and signed the informed consent. The inclusion criteria vessels. But the disadvantage of ovule preparation is make discom-
include (1) there is a clinical complaint of abnormal vaginal dis- fort during intercourse because of molten ovule propolis. There-
charge (2) married women, aged 20–50 years old; (3) positive fore, it is recommended to apply ovules before intercourse or to
hyphae/pseudo hyphae and culture of vaginal swab; (4) not preg- use a condom during intercourse.
nant; (5) not received treatment. Forty subjects were randomly The results of the positive laboratory evaluation included posi-
divided into two groups: the group receiving treatment with ovule tive hyphae/pseudohyphae and culture on Sabouraud Dextrose
propolis (n = 20) and the control group receiving standard treat- Agar medium from a vaginal swab were shown in Fig. 2. The results
ment with nystatin (n = 20) intra vagina, once a day before sleep, of identifying of the Candida species isolated on Sabouraud Dex-
for seven days, respectively. trose Agar medium and chromogenic agar medium from 40
144 S. Farida et al. / Saudi Journal of Biological Sciences 27 (2020) 142–146

Table 1
Identification of Candida species isolated from vaginal swab.

Organism Number of Group therapy Group therapy

patients (percent) Propolis Nystatin
C. albicans 38 (95%) 19 (95%) 19 (95%)
C. glabrata 1 (2.5%) – 1 (5%)
C. crusei 1 (2.5%) 1 (5%) –

Table 2
The number of dropped out subjects between groups.

Group Number of Number of dropped out (DO) subjects

therapy subjects
Propolis 20 2 (one DO subject was caused by C. crusei)
Nystatin 20 3 (all DO subjects were caused by C. albicans)

Fig 1. Vaginal suppository (ovule) containing propolis wax 5%.

Table 3
patients are shown in Table 1. Those isolates showed that 38 (95%) Laboratory evaluation (culture of vaginal swab) before and after therapy.
were identified as C. albicans, 1 (2.5%) as C. krusei, and 1 (2.5%) as Group therapy Culture test before therapy Culture test after therapy
Candida glabrata. The results were similar to a multicenter study Propolis (n = 18) (+) ( )
by Sobel et al. (2004), Sobel (2016) who reported that C. albicans Nystatin (n = 17) (+) ( )
was the most common cause of vaginal candidiasis (>90%), fol-
lowed by 3% as C. glabrata, 0.2% as C. krusei, although the 5 most
common pathogens causing of superficial candidiasis were C. albi- out. The finding of this study was supported by Dota et al., 2011,
cans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis (Berkow Berkow et al., 2015, Gavanji et al., 2011; Gavanji and Larki, 2017;
and Lockhart, 2017). However, the distribution patterns of Candida Soekanto et al., 2018 who showed the antifungal activity of Propo-
species was different from the study on Ethiopia’s women by Bitew lis. This finding was also supported by Al-Waili et al., 2012 who
and Abebaw (2018) who reported that the most frequent isolate reported the propolis from Saudi and Egypt that combined with
was C. albicans for 58.6%, followed by C. krusei 17.2%, and C. glab- honey had the synergistic effect toward drug multi-resistant of C.
rata 3.4%. albicans. This study also demonstrated that 100% C. albicans was
The number of dropped out subject during treatment observa- susceptible to Indonesian Propolis wax of stingless bee Tetragonula
tion was shown in Table 2. Five subjects dropped out and loss to sp. from Sulawesi-Indonesia, while the study by Bitew and Abebaw
follow up because they did not come for laboratory evaluation (2018) demonstrated that 2% of C albicans was resistant to flucona-
(culture and vaginal swab) after seven days of treatment, two sub- zole and 33.3% of C. krusei was resistant to fluconazole. This anti-
jects from the propolis group and three subjects from the nystatin candida effect of propolis wax due to polyphenols compounds in
group. One dropped out subject from group therapy of propolis propolis wax which has proven effective in inhibiting C. albicans
was caused by infection of C. crusei isolate, while all dropped out reaching 76% in concentrations of 79.43 mg/ml (Hudnall, 2007).
subject from nystatin group were caused by infection of C. albicans Moreover, in such a small amount, polyphenols in wax propolis
isolate. of Tetragonula sp. have antioxidant activity (Pratami et al., 2018,
The evaluation of seven days of treatment by ovule containing Christina et al., 2018). Our results also showed that Tetragonula
propolis wax 5% compared to standard therapy in inhibiting C. albi- sp. propolis from Sulawesi has different properties compared with
cans’ growth are shown in Table 3. The results of this study showed others propolis (Miyata et al., 2019, Alqarni et al., 2019). Several
no significant difference in culture evaluation (culture of C. albi- new compounds was found in the propolis, such as Sulawesin A
cans’s growth on Sabouraud Dextrose Agar medium) from vaginal and B that not found in other propolis (Miyata et al., 2019).
candidiasis patients who have treated ovule propolis wax 5% com- The finding of this study was supported by Mahadewi et al.
pared to standard therapy nystatin, respectively. (2017) that showed the level of flavonoid compounds of the Tetra-
The results of this study indicated the effectivity of ovule propo- gonula propolis wax from Sulawesi was higher than propolis from
lis wax 5% from Tetragonula sp. to inhibit the growth of C. albicans, Rumania, Taiwan, Brazil, China (Huang, 2002). The bioactive com-
but the effect of propolis on C. krusei did not evaluate due to drop pound in propolis containing polyphenols, terpenes and flavonoids

Fig 2. Positive hyphae/pseudohyphae (A); positive of Candida’s growth on Chrom Agar medium (B); positive of Candida’s growth on SDA medium (C).
 S. Farida et al. / Saudi Journal of Biological Sciences 27 (2020) 142–146 145

have anti-inflammatory, antimicrobial, antioxidant and antiviral cells via inhibition of purine nucleoside phosphorylase. Metab. 9 (4). https://doi.
org/10.3390/metabo9040075.
activities (Cardoso et al., 2010, Kim et al., 2011, Odonez et al.,
Alves de Lima, N.C., Ratti, B.A., Souza Bonfim Mendonça, P., Murata, G., Araujo
2011). Furthermore, Mahadewi et al., also reported that Indonesian Pereira, R.R., Nakamura, C.V., et al., 2018. Propolis increases neutrophils
propolis wax contained anti-fungal marker compounds such as response against Candida albicans through the increase of reactive oxygen
thymol, curcumene, tetraline, and E-p-coumaric acid that had species. Future Microbiol. 13, 221–230. https://doi.org/10.2217/fmb-2017-
0112.
potential as anti-candida. This result was also supported by Da Bankova, V., Castro, S. De, Marcucci, M., 2000. Propolis: Recent advances in
Silva et al. 2015 that showed terpenes compound in thymol had chemistry and plant origin. Apidologie 31 (1), 3–15. https://doi.org/10.1051/
MIC to C. albicans 64 mg/ml. Unfortunately, we cannot evaluate apido:2000102.
Bankova, V., Popova, M., Trusheva, B., 2014. Propolis volatile compounds: chemical
the effectivity of ovule propolis to inhibit the growth of C. krusei diversity and biological activity: a review. Chem. Cent. J. 8 (1), 28. https://doi.
because the subject did not come to laboratory evaluation (culture org/10.1186/1752-153X-8-28.
and vaginal swab) after seven days of treatment. The recent studies Berkow, E.L., Lockhart, S.R., 2017. Fluconazole resistance in Candida species: a
current perspective. Infect Drug Resist. 10, 237–245.
reported that the mechanism of action of propolis wax as an anti- Bitew, A., Abebaw, Y., 2018. Vulvovaginal candidiasis: species distribution of
candida by inhibition the production of biofilm matrix (Capoci Candida and their antifungal susceptibility pattern. BMC Women’s Health 18,
et al., 2018) and germ tube formation as virulence attribute 94. https://doi.org/10.1186/s12905-018-0607-z.
Bittencourt, M.L.F., Ribeiro, P.R., Franco, R.L.P., Hilhorst, H.W.M., de Castro, R.D.,
(Haghdoost et al., 2016) of C. albicans. Moreover, Alves de Lima Fernandez, L.G., 2015. Metabolite profiling, antioxidant and antibacterial
et al., 2018 showed that propolis can improve the immune activities of Brazilian propolis: Use of correlation and multivariate analyses to
response againts C. albicans by increasing the microbial activity identify potential bioactive compounds. Food Res. Int. 76 (3), 449–457. https://
doi.org/10.1016/j.foodres.2015.07.008.
of neutrophils. To ensure the effectivity of anti-candida effect of
Cardoso, R.L., Maboni, F., Machado, G., Alves, S.H., de Vargas, A.C., 2010.
propolis wax in vaginal candidiasis patients, we will continue the Antimicrobial Activity of Propolis Extract against Staphylococcus coagulase
clinical study with enough sample size. positive and Malassezia pachydermatis of canine otitis. Vet. Microbiol 142,
432–434.
Christina, D., Hermansyah, H., Wijanarko, A., Rohmatin, E., Sahlan, M., Pratami, D.K.,
Mun’im, A., 2018. Selection of propolis Tetragonula sp. extract solvent with
4. Conclusion flavonoids and polyphenols concentration and antioxidant activity parameters.
In: AIP Conference Proceedings, Vol. 1933. http://doi.org/10.1063/1.5023967.
Based on these results, the ovule propolis wax from Tetragonula da Silva, L.A., Pezzini, B.R., Soares, L., 2015. Spectrophotometric determination of the
total flavonoid content in Ocimum basilicum L. (Lamiaceae) leaves. Pharmacogn
sp. at concentration 5% has a beneficial effect of being imple- Mag. 11 (41), 96–101. https://doi.org/10.4103/0973-1296.149721.
mented and developed as an anti-candida agent for vaginal can- Dota, D., Consolaro, L., Svidzinski, E., Bruschi, M.L., 2011. Antifungal activity of
didiasis therapy. The anti-candida effect of propolis wax due to brazilian propolis microparticles against yeast isolated from vulvovaginal
candidiasis. Evidence-Based Complement and Alternative Med. Article ID
their phytochemical compounds. 201953, 8 pages http://doi.org/10.1093/ecam/neq029.
Farnesi, A.P., 2009. Effects of stingless bee and honey bee propolis on four species of
Ethical approval bacteria. Genet Mol Res. 635–640. https://doi.org/10.7324/JAPS.2016.60206.
Gavanji, S., Asgari, M.J., Vaezi, R., Larki, B., 2011. Antifungal effect of the extract of
propolis on the growth of three species of Epidermophyton flucosum,
All research methods used have been approved by the Ethics Trichophyton violaseum and Trichophytontonsorans in laboratory
Commission of the Faculty of Medicine, Universitas Indonesia, environment. Afr. J. Pharm. Pharmacol. 5, 2642–2646.
Gavanji, S., Larki, B., 2017. Comparative effect of propolis of honey bee and some
Jakarta, Indonesia, with approval number No. 810/UN.2.FI/ETIK/ herbal extracts on Candida albicans. Chin. J. Integr. Med. 23 (3), 291–1207.
2017. https://doi.org/10.1007/s11655-015-2074-9. Epub 2015 Jul 7.
Haghdoost, N.S., Salehi, T., Khosravi, Z.A., Sharifzadeh, A., 2016. Antifungal activity
and influence of propolis against germ tube formation as a critical virulence
Acknowledgment attribute by clinical isolates of Candida albicans. J. Mycol. Med. 26 (4), 298–305.
https://doi.org/10.1016/j.mycmed.2015.11.004. Epub 2016 Oct 24.
Hudnall, A.M., 2007. United State Patent No. US 7294351.
The authors are very grateful to the Head of Tasikmalaya Health Kim, M.J., Kim, C.S., Kim, B.H., Ro, S.B., Lim, Y.K., Park, S.N., Cho, E., Ko, J.H., Kwon, S.S.,
Service (Dinas Kesehatan Tasikmalaya) and the Head of Commu- Ko, Y.M., Kook, J.K., 2011. Antimicrobial effect of Korean Propolis against the
mutans Streptococci isolated from Korean. J Microbiol. 49, 161–164.
nity Health Center (Puskesmas) Tawang-Tasikmalaya for arranging Lemos, J.A., 2009. Susceptibility testing of Candida albicans isolated from
the subjects of this study. The financial funding of this research oropharyngeal mucosa of HIV+ patients to flukonazol, amphotericin B and
was supported by the Directorate of Research and Community Ser- caspofungin. Braz. J. Microbiol. 163–169. https://doi.org/10.1590/S1517-
838220090001000028.
vice Grant Universitas Indonesia and The Ministry of Research,
Lotfy, M., 2006. Biological activity of bee propolis in health and disease. Asian Pac. J.
Technology and Higher Education of the Republic of Indonesia Cancer Prev. 7, 22–31.
[grant numbers 464/UN2. R3.1/HKP05.00/2018]. This article’s pub- Mahadewi, A.G., Christina, D., Hermansyah, H., Wijanarko, A., Farida, S., Adawiyah,
lication is partially supported by the United States Agency for R., et al., 2017. Selection of discrimination marker from various propolis for
mapping and identify anti Candida albicans activity. AIP. Conf. Proc. 1933 (1),
International Develpoment (USAID) through the Sustainable 20005. https://doi.org/10.1063/1.5023939.
Higher Education Research Alliance (SHERA) Program for Universi- Mitchell, H., 2004. ABC of Sexulally transmitted infections: vaginal discharge-
tas Indonesia’s Scientific Modelling, Application, Research and causes, diagnosis, and treatment. BMJ. 328 (7451), 1306–1308. https://doi.org/
10.1136/bmj.328.7451.1306.
Training for City-centered innovation and Technology (SMART Miyata, R., Sahlan, M., Ishikawa, Y., Hashimoto, H., Honda, S., Kumazawa, S., 2019.
CITY) Project, Grant #AID-497-A-1600004, Sub Grant #IIE- Propolis components from stingless bees collected on south sulawesi,
00000078-UI-1. indonesia, and their xanthine oxidase inhibitory activity. J. Nat. Prod. 82 (2),
205–210. https://doi.org/10.1021/acs.jnatprod.8b00541. Epub 2019 Feb 5.
Nina, N., Quispe, C., Jiménez-Aspee, F., Theoduloz, C., Giménez, A., Schmeda-
Hirschmann, G., 2016. Chemical profiling and antioxidant activity of Bolivian
References propolis. J. Sci. Food Agric. 96 (6), 2142–2153. https://doi.org/10.1002/jsfa.7330.
Nurul, Qomariyah, S., 2001. Infeksi Saluran Reproduksi (ISR) pada Perempuan
Al-Fattani, M.A., Douglas, L.J., 2006. Biofilm matrix of Candida albicans and Candida Indonesia.. Depok : Pusat Komunikasi Kesehatan Perspektif Gender.
tropicalis: chemical composition and role in drug resistance. J. Med. Microbiol. Ordonez, R.M., Zampini, I.C., Moreno, M.I., Isla, M.I., 2011. Potential application of
55, 999–1008. nothern argentine propolis to control some phytopathogenic bacteria.
Al-Waili, N., Al-Ghamdi, A., Ansari, M.J., Al-Attal, Y., Salom, K., 2012. Synergistic Microbiol. Res.
effects of honey and propolis toward drug multi-resistant Staphylococcus Pratami, D.K., Mun’im, A., Sundowo, A., Sahlan, M., 2018. Phytochemical profile and
aureus, Escherichia coli and Candida albicans isolates in single and antioxidant activity of propolis ethanolic extract from tetragonula bee.
polymicrobial cultures. Int. J. Med. Sci. 9 (9), 793–800. https://doi.org/ Pharmacognosy J. 10 (1), 128–135. https://doi.org/10.5530/pj.2018.1.23.
10.7150/ijms.4722. Epub 2012 Oct 26. Siqueira, A.B., Rodriguez, L.R., Santos, R.K., Marinho, R.R., Abreu, S., Peixoto, R.F.,
Alqarni, A.M., Niwasabutra, K., Sahlan, M., Fearnley, H., Fearnley, J., Ferro, V.A., et al., Gurgel, B.C., et al., 2015. Antifungal activity of propolis against Candida species
2019. Propolis exerts an anti-inflammatory effect on PMA-Differentiated THP-1 isolated from cases of chronic periodontitis. Braz Oral Res. 29. https://doi.org/
146 S. Farida et al. / Saudi Journal of Biological Sciences 27 (2020) 142–146

10.1590/1807-3107BOR-2015.vol29.0083, pii: S1806-83242015000100278. Trusheva, B., Popova, M., Koendhori, E.B., Tsvetkova, I., Naydenski, C., Bankova, V.,
Epub 2015 Jul 3. 2011. Indonesian propolis: Chemical composition, biological activity and
Sobel, J.D., Wiesenfeld, H.C., Martens, M., Danna, P., Hooton, T.H., Rompalo, A., et al., botanical origin. Natural product research. Nat Prod Res. 25 (6), 606–613.
2004. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. https://doi.org/10.1080/14786419.2010.488235.
N. Engl. J. Med. 351, 876–883. Uppuluri, P., Pierce, C.G., Lopez-Ribot, J.L., 2009. Candida albicans biofilm formation
Sobel, J.D., 2016. Recurrent vulvovaginal candidiasis. Am. J. Obst. Gynecol., 15–22 and its clinical consequences. Future Microbiol. 4, 10e.
Soekanto, S.A., Bachtiar, E.W., Ramadhan, A.F., Febrina, R., Sahlan, M., 2018. The Velikova, M., Bankova, V., Tsvetkova, I., Kujumgiev, A., Marcucci, M.C., 2000.
effect of propolis honey candy on C. Albicans and clinical isolate biofilms Antibacterial ent-kaurene from Brazilian propolis of native stingless bees.
viability (in-vitro). In: AIP Conference Proceedings. AIP Publishing, p. 30004. Fitoterapia 71 (6), 693–696. https://doi.org/10.1016/S0367-326X (00)00213-6.