Chemical characterization and antimicrobial activity of propolis in the world.
Abstract
Candida species live as commensal in humans and cause candidiasis in the presence of some predisposing factors. They are the most common among systemic mycosis agents. Currently, existing drugs used in the treatment of Candida infections may develop resistance, especially azole group compounds, and may lead to serious side effects and problems that may occur in therapy. Therefore, alternative natural treatment methods with very low side effects or no side effects should be considered. Propolis is one of the most natural products which has been used as a natural drug in traditional medicine for the treatment of various diseases for thousands of years. Propolis is a sticky resinous substance collected and deposited by bees from plant buds, leaves, and stems. Propolis has a wide spectrum of biological activities such as antibacterial, antifungal, antiviral, antiparasitic, anti-inflammatory, immunomodulatory, and antioxidant. The compounds responsible for the biological activity of propolis are thought to be flavonoids, caffeic acid and esters, phenolic compounds, aromatic acid and esters. In this chapter, I aimed to investigate the antifungal activity of propolis against Candida species. Considering the safety, low cost, and usefulness of propolis, it should be considered as an alternative natural treatment method.
Keywords
- propolis
- antifungal activity
- Candida species
1. Introduction
1.1 Candida species
1.2 Candida virulence factors
The virulence factors of
1.3 Antimicrobial resistance of Candida species
Antimicrobial resistance is a threat worldwide and is a major public health problem. Antifungal selection is very important in several fungal infections, because in universal treatment, various problems such as side effects, drug interaction and toxicity, and antifungal resistance such as azole and polygenic derivatives may occur related to conventional treatments. The rapidly increasing antimicrobial resistance in the world results in an increase in the number of diseases and deaths [5, 7, 9, 13]. Therefore, alternative treatment methods with natural products due to very low side effects or no side effects should be considered. In recent years, the increase in antimicrobial resistance and its side effects and the increase in cancer cases have led scientists to seek alternative natural treatments in modern medicine.
2. Apitherapy
Bee products have been used for treatment in folk medicine for centuries. Apitherapy is a type of alternative therapy that bee products are used that obtained directly from honeybees. Bee products such as honey, royal jelly, beeswax, bee venom, propolis, and pollen are thought to be beneficial to humans due to their biological and pharmacological properties [14, 15, 16]. It has been used all over the world, especially in China, Japan, and Korea in recent years. Apitherapy has been used for thousands of years. Bee venom therapy used since ancient times in Egypt, Greek, China, and Central Asia for various types of pain and arthritis pain and it is anti-inflammatory and helps relieve pain. Clinical studies have shown that bee venom treatment reduces the need for medication and reduces the risk of pain and recurrence. Diseases such as infections, wounds, burn, lupus, arthritis, shingles, pain, and muscle and joint disorders are some of the areas of apitherapy [16, 17]. Modern herbalists recommend propolis for the treatment of gastrointestinal ulcers and to increase the body’s natural defense mechanisms against infections due to its antibacterial, antifungal, antiviral, anti-inflammatory, and liver protective properties [16]. Today, there are extensive apitherapy centers in China, Romania, and some Eastern European countries where diseases are treated with bee products [16]. With the regulation on traditional and complementary medicine practices published in 2014, in Turkey, apitherapy courses have been organized and apitherapy centers have begun to be established.
3. Biological properties of propolis
Propolis is a useful and versatile natural, non-toxic, low-cost bee product that has been used to cure diseases, and only bees can make propolis. It is used in ancient times in Egypt, Greece, Rome, Europe, and North Africa in the treatment of various diseases or to reduce their side effects. The Greeks used propolis as an antiseptic and in wound healing, while the Assyrians used it in wound and tumor treatments. Egyptians used propolis to mummify the dead [16, 18]. Propolis in Greek “pro” means “in defense for” and “polis” means “city” [19]. Propolis is a resinous and waxy substance collected by bees from the leaves, stems, buds, and similar parts of plants, which has a nice and pungent smell and does not dissolve in water. Propolis wax at 15−20°C, at 30−40°C sticky and gum-like. Generally, it melts at 60–70°C, when frozen times take a hard and brittle structure. Propolis gains a strong and sticky property due to the change of the structure of the collected plant resin by the bees [17, 18]. It is extremely rich in antioxidant content. Bees use propolis as an agent with antibacterial, antiviral, and antifungal activities to maintain a sterile environment in the hive and to protect the health of bees. Bee propolis is used the coat the inside of the hive, close the cracks, harden and repair the edges of the honeycombs, make the hive entrance hole easily defendable, and clean and polish the cells before the queen lays her eggs. It is brittle and hard in the cold but can become sticky when in hot environment. The structure of propolis consists of 50% resin and herbal balm, 30% wax, 10% essential and aromatic oils, 5% pollen, 5% protein, and other substances [19, 20, 21, 22, 23] (Figure 1). There are more than 300 compounds in the content of propolis. These are polyphenols (flavonoids, phenolic acid, and its esters), terpenoids, steroids, aromatic acid, and its esters, alcohols, aldehydes, chalcones, hydrocarbons, quinones, amino acids, coumarin, ketones, essential fatty acids, vitamins (B1, B2, B6, A, C, and E), and minerals (calcium, magnesium, potassium, sodium, manganese, selenium, iron, zinc, and copper). Polyphenols and terpenoids are considered the most active compounds. The flavonoids are antimicrobial effect, and they include chrysin, pinocembrin, apigenin, galangin, pinostrobin, quercetin, kaempferol, tectochrysin, and other similarly structured compounds. The beneficial feature of propolis is usually due to the flavonoid groups it contains [19, 20, 23, 24, 25]. Flavonoids are generally found in photosynthesizing cells. Since they are secondary plant metabolites and cannot be synthesized by humans, they are important for human nutrition. Aromatic acids are among the other important components of propolis, and the most important ones are caffeic acid, cinnamic acid, ferulic acid, benzoic acid, and coumaric acid [24, 25]. Propolis has different and richer content than bee pollen. Propolis supports the immune system with its antimicrobial, anti-inflammatory, and antioxidant properties [23]. Propolis can be protective against tumor formation by preventing the structural change of the cell by neutralizing free oxygen radicals with its antioxidant property in cellular damages caused by oxidant. The effects on the cardiovascular system and eye health are also based on this feature [26, 27, 28, 29]. Cinnamic acid and its active ingredients, galangin, pinocembrin, and cumaric acid in propolis are involved in a wide therapeutic spectrum. It shows antimicrobial, antifungal, and antibacterial effects [30, 31, 32]. Propolis and its extracts have numerous procedures in treating various diseases due to its antiseptic, antibacterial, antifungal, antiviral, antiparasitic, antioxidant, anti-inflammatory, antitumor, antiulcer, anticancer, scar-forming, tissue regeneration, local anesthetic, immunomodulatory and cytostatic activity. Therefore, it has been used in foods and beverages for the prevention of cancer, heart diseases, and diabetes [19, 20, 23, 33]. There are also harmful effects of propolis besides the beneficial effects. Sensitive as a result of allergic reactions in humans occurring in different parts of the body such as mouth, tongue, hand, back, feet such as eczema, dermatitis (skin crusting, watery picking, itching, pain, etc.) cough, etc. symptoms can be seen [18, 27].
The structure of propolis varies according to the type of plant it is collected from, the way it is collected and used by the bee, and the methods used. Propolis should not be consumed as it is produced in the hive. Since raw propolis contains unwanted parts such as bee dead, larval remains, and plant parts, it is pre-purified by extraction with suitable solvents before use. In order for people to benefit from this product, it must be processed. Since it is a natural product and has a characteristic smell [19].
Since the chemical structure of propolis changes according to the plant source from which it is collected, different plant species can be propolis sources. Particularly in continental climate regions, mainly Populus spp., Abies spp., Acer spp., Alnus spp., Ulmus spp., Tilia spp., Pinus spp., Betula spp., Salix spp., Corylus spp.,
4. Collection time of propolis
The best time to harvest propolis from the hives is between September and October. Because before the bees enter the winter months, the market holes in the hive should be as small as possible with the help of propolis in order to protect themselves in the best way possible, and they are harvested by beekeepers when the time comes. It is reported that propolis production may be more active with the onset of the rainy season in tropical climates. Phenolic compounds containing flavonoid and cinnamic acid derivatives are predominantly found in propolis obtained from temperate regions. While diterpenes and prenylated compounds are very rare in temperate zone propolis, it has been reported that they are found together with lignans, flavonoids, and other group compounds in tropical propolises obtained from South America [27].
4.1 Extraction methods of propolis
The composition of the propolis varies according to the type of solvent used and the extraction method. Solvents that do not pose a threat to health should be used in propolis extracts offered for human consumption. There may be variations in the biological effects of different solvents depending on the solubility properties of different components in propolis [35, 36]. Ethanol is the most preferred propolis extract, besides water, methanol, glycerol, methylene chloride, hexane, acetone, olive oil, and propylene glycol are other preferred solvents for the extraction of propolis. One of the solvents in the legislation, water is not preferred because it cannot dissolve the components in propolis sufficiently. Solubility in water-based propolis is only 1%. Like the tween used to dissolve chemicals with detergent, properties are harmful to health. In the case of using water as a solvent, the expected benefits cannot be achieved due to the low rate of penetration of caffeic acid, phenyl ester, and some important flavonoids (chrysin, galangin, pinobanksin, pinocembrin) in the content. Ethanol, glycerol, and propylene glycol alcohol- derived solvents. The reason why ethanol is mostly preferred in propolis extraction is that it dissolves more bioactive substances. High-pressure liquid chromatography (HPLC) with a diode array detector (DAD) (HPLC-DAD), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and many chromatographic methods are used to examine the chemical structure of propolis. It is reported that HPLC-DAD and high-pressure liquid chromatography-mass spectrometry (HPLC-MS) give good results due to the polar nature of propolis (the molecular structure generally contains in OH− groups) [17, 35, 36]. Therefore, when interpreting the results of the studies, which solvent is used should be considered.
5. Studies on the chemical composition and antimicrobial activity of propolis in the world
There are many studies on the chemical structure and antimicrobial effect of propolis in the world [21, 23, 24, 25, 26, 27, 28, 29, 33, 34, 35, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53] (Table 1). Popova et al. [21] searched 114 propolis specimens from different countries to determine the chemical characteristics of poplar propolis and formed two groups according to the data obtained. Central and Southern Europe, Turkey, Syria, and other locations in continental climate (97 samples) first group, in the same zone as colder regions (Northern and mountains regions; Baltic Countries, England, Ukraine, Siberia, Canada, and Sweden) the second group. Groups varied considerably in phenolic and flavonoid content. Northern and mountainous region propolises were found to have lower values of 25% phenolic, 38% flavone and flavonol, and 17% flavonone/dihydroflavonol compared with the first group propolis. However, no significant differences were observed between the antimicrobial activities of all specimens. AL-Ani et al. [23] studied the chemical components, biological activities, and synergistic effects of antibiotics in different plant-derived propolis samples collected from various regions of Europe; Ireland, Germany, and Czech Republic. The chemical components of the ethanol extract of propolis (EEP) and water extract of propolis (WEP) were analyzed by gas liquid chromatography-mass spectrometry (GLC-MS) and high-performance liquid chromatography (HPLC), and more than 100 different phytochemicals were obtained from the ethanol and water extracts. In Irish propolis identified many flavonoids like pinocembrin, chrysin, and galangin were as well as significant amounts of nonacosane, heptacosane, pentacosane, guaiol, alpha-bisabolol, and caffeic acid. German propolis contained several acids such as benzoic acid, cinnamic acid, salicylic acid, myristic acid, 4-methoxyphenyl propanoic acid, hexadecanoic acid, and dodecanoic acid. Also, in Czech propolis detected as dominant compounds flavonoids such as galangin, pinocembrin, and chrysin and phenyl carboxylic acids such as benzoic acid, caffeic acid, cinnamic acid, and
5.1 Studies on the chemical analysis and antimicrobial activity of propolis in Turkey
Numerous studies are carried out on the chemical composition and antimicrobial activity of propolises produced in Turkey [15, 30, 32, 36, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64] (Table 2). Bayram et al. [15] investigated the chemical analysis and antimicrobial action of propolis from Hakkari region (Eastern Anatolia) of Turkey on some pathogens by GC–MS. They detected more the total flavonoid amount than the other compounds such as terpenes, ketones, alcohols, hydrocarbons, aromatic acids, cinnamic acids, and their esters and aliphatic acids and esters. They found pinocembrin (9.16%), pinostrobin chalcone (8.85%), ethyl oleate (8.15%), and chrysin (5.82%) as major flavonoids. Kartal et al. [54] investigated the antimicrobial activities of propolis samples collected from Ankara (Kazan) and Muğla (Marmaris) regions of Turkey, by GC–MS chromatography method and detected 24 different compounds in the samples. They prepared four different ethanol extracts (using 30%, 50%, 70%, and 96%) from propolis samples and examined the effects of these extracts on seven Gram-positive, four Gram-negative, and fungal culture. They stated that the samples taken from Ankara-Kazan showed stronger antimicrobial activity compared with the Muğla-Marmaris samples, and they stated that the chemical content of Ankara-Kazan propolis was similar to the bud secretions of Populus species. They explained that the observed activity was mostly due to caffeic acid and its esters. Also, the active components of the Mugla-Marmaris samples were determined as isopimaric acid. The other study on the chemical content of Turkish propolis was conducted by Sorkun et al. [55] and in this study, samples from different regions of Turkey (Bursa, Erzurum-Askale, Gumushane-sogutagil and Trabzon-Caglayan) were collected and their chemical analyzes were performed by GC–MS. According to the results of this study, propolis samples taken from Trabzon and Gumushane regions have similar chemical content, and the basic components are aromatic and aliphatic acids and their esters and ketones, Erzurum propolis has a different structure and aromatic acid esters and alcohols are the basic components, and it is better than other samples. It was found to contain more amino acids. In the samples collected from Bursa region, it was determined that flavonones, terpenoids, flavones, aromatic acid esters, and ketones were the main amounts. In the samples from Bursa region, flavones, flavonones, and ketones were detected in very rich amounts. Silici and Kutluca [56] investigated the chemical profile and antimicrobial effect of propolis collected by three different honeybees in the same region and the same season in Erzurum (East Anatolia) with the GC–MS method and 48 compounds were identified 32 being new for propolis. They found high aromatic acid esters and amino acid contents and strong Gram-positive activity in
Region | Main compounds | Activity | References |
---|---|---|---|
First group: Central and Southern Europe, Turkey, Syria, and other locations in continental climate | First group: phenolic, flavone and flavonol, flavonone/dihydroflavonol | Same antimicrobial activity; Gram-positive bacteria | Popova et al. [21] |
Second group: Northern and mountains regions; Baltic Countries, England, Ukraine, Siberia, Canada, and Sweden. | Second group: lower values than first group 25% phenolic, 38% flavone, and flavonol, 17% flavonone/dihydroflavonol | Same antimicrobial activity; Gram-positive bacteria | |
Ireland | Flavonoids, galangin, and caffeic acid | Gram-positive bacterial and antifungal effect | AL-Ani et al. [23] |
Germany | Several acids, benzoic acid, cinnamic acid, and salicylic acid | Gram-positive bacterial and antifungal effect | |
Czech Republic | Flavonoids | Gram-positive bacterial and antifungal effect | |
Germany | All of samples have similar flavonoids and phenolic esters | Highest antimicrobial activity on | Hegazi et al. [33] |
France | Low effect on all pathogens | ||
Austria | Highest activity to | ||
Six different regions of Turkey: | – | Popova et al. [37] | |
Artvin, Erzurum, Adana | Low phenolic and very low flavonoid compounds | ||
İzmir, Kayseri, Yozgat | Very similar phenolic and flavonoid content | ||
Bulgarian propolis Turkish propolis | Similar features: The samples are rich in caffeic acid and ferulic acid | Antibacterial and antifungal | Velikova et al. [38] |
Iran | Pinocembrin, acetate, pinobanksin, pinobanksin-3, pinostrobin flavonones, and flavones | – | Mohammadzadeh et al. [39] |
Iran | Pinocembrin, caffeic acid, kaempferol, galangin, and chrysin | Gram-positive bacterial and antifungal activity | Yaghoubi et al. [40] |
Egypt | – | Antibacterial and high antifungal effect | Gharib et al. [41] |
Lebanon | – | Antibacterial (bacteriostatic) and antifungal (fungicidal) effect | Chamandi et al. [42] |
Brazilian propolis | Cinnamic acid derivatives and flavonoids | Antibacterial effect | Moncla et al. [43] |
Uruguayan propolis | Flavonoids, phenolic acid esters, and aromatic acids | – | Kumazawa et al. [44] |
Japan | Total phenolic compounds | Antioxidant activity | Hamasaka et al. [45] |
Region | Main compounds | Activity | References |
---|---|---|---|
Hakkari | Total flavonoids | Bayram et al. [15] | |
Ankara (Kazan) | Caffeic acid and esters | Higher antimicrobial activity | Kartal et al. [54] |
Muğla (Marmaris) | Isopimaric acid | Antimicrobial activity | |
Bursa | Flavonones, terpenoids, flavones, aromatic acid, and their esters and ketones | – | Sorkun et al. [55] |
Erzurum-Askale | Aromatic acid esters and alcohols | ||
Gumushane-Sogutagil | Aromatic acids, aliphatic acids, and their esters and ketones | ||
Trabzon-Caglayan | Aromatic acids, aliphatic acids, and their esters and ketones | ||
Erzurum | High aromatic acid esters and amino acid contents | Strong Gram-positive effect ( | Silici and Kutluca [56] |
Trabzon | Flavonoids, crysin, apigenin, and flavonones | All of propolis specimens high antibacterial effect on | Katırcıoglu and Mercan [57] |
Erzurum | Flavonoids, crysin, apigenin, and flavonones | ||
Tekirdag | Flavonoids, crysin, apigenin, flavonones, and naringenin | ||
Different geographic region of Turkey | Flavonoids, aromatic alcohols, aromatic acids and esters, terpens, aliphatic carboxylic acids, and esters | High antibacterial activity to | Temiz et al. [58] |
5.2 Antifungal properties of propolis and mechanisms of action
The mechanisms of action of propolis are shown in Figure 2. The studies have reported that compounds such as flavonoids (especially pinocembrin) and phenolic compounds present in honey and propolis are responsible for their antifungal activity by affecting cytoplasmic membrane permeability and resulting in total leakage of cell components and inorganic ions, leading to complete cell death [46, 47, 48]. The ability of
5.3 Studies on the antifungal properties of propolis
Investigation on the antifungal efficacy of propolis is shown in Table 3. Hegazia et al. [33] found the highest antifungal activity of propolis on C. albicans, which was detected in Austrian propolis. Ota et al. [51] investigated the antifungal effect of Brazilian propolis against
Region | Mechanism of action | Activity | References |
---|---|---|---|
Austria | All of propolis specimens inhibit the growth | Perfect effect against | Hegazi et al. [33] |
Germany | Antifungal action | ||
France | Low antifungal activity | ||
Brazilian propolis | – | Highest fungicidal action | Ota et al. [51] |
Iran | – | Higher fungicidal effect | Yarfani et al. [52] |
Brazil | – | Fungicidal activity | Oliveira et al. [53] |
Spain | Inhibit the biofilm formation | Excellent fungicidal activity | Fernandez-Calderon et al. [72] |
Brazil | Inhibit the biofilm formation | Antifungal activity | Capoci et al. [73] |
Brazil | Inhibit the biofilm formation | Predominantly fungistatic effect | Freires et al. [74] |
Thailand | Inhibit hyphal adhesion, invasion, and biofilm formation | Anticandidal effect | Iadnut et al. [75] |
In conclusion, resistance to antifungals used in traditional treatment such as azole groups and also echinocandins in
References
- 1.
Mohandas V, Ballal M. Distribution of Candida species in different clinical samples and their virulence: Biofilm formation, proteinase and phospholipase production: A study on hospitalized patients in Southern India. Journal of Global Infectious Diseases. 2011;3 (1):4-8 - 2.
Brandt ME, Lockhart SR. Recent taxonomic developments with Candida and other opportunistic yeasts. Current Fungal Infection Reports. 2012;6 (3):170-177 - 3.
Pfaller MA, Andes DR, Diekema DJ, Horn DL, Reboli AC, Rotstein C, et al. Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2,496 patients: Data from the Prospective Antifungal Therapy (PATH) registry 2004-2008. PLoS One. 2014;9 :e101510. DOI: 10.1371/journal.pone.0101510 - 4.
Naglik JR, Challacombe SJ, Hube B. Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiology and Molecular Biology Reviews. 2003;67 :400-428 - 5.
Vila T, Romo JA, Pierce CG, McHardy SF, Saville SP, Lopez-Ribot JL. Targeting Candida albicans filamentation for antifungal drug development. Virulence. 2017;8 (2):150-158 - 6.
Kadosh D, Lopez-Ribot JL. Candida albicans : Adapting to succeed. Cell Host & Microbe. 2013;14 :483-485 - 7.
Cleveland AA, Harrison LH, Farley MM, Hollick R, Stein B, Chiller TM, et al. Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008-2013: Results from population-based surveillance. PLoS One. 2015;10 (3):e0120452 - 8.
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study. Clinical Infectious Diseases. 2004; 39 :309-317 - 9.
Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: A persistent public health problem. Clinical Microbiology Reviews. 2007; 20 :133-163 - 10.
Kojic EM, Darouiche RO. Candida infections of medical devices. Clinical Microbiology Reviews. 2004;17 (2):255-267 - 11.
Thompson GR, Patel PK, Kirkpatrick WR, Westbrook SD, Berg D, Erlandsen J, et al. Oropharyngeal candidiasis in the area of antiretroviral therapy. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2010; 109 :488-495 - 12.
Sudbery P, Gow N, Berman J. The distinct morphogenic states of Candida albicans . Trends in Microbiology. 2004;12 (7):317-324 - 13.
Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence. 2013;4 (2):119-128 - 14.
Albayrak S, Albayrak S. Propolis: Natural antimicrobial matter. Ankara Üniversitesi Eczacılık Fakültesi Dergisi. 2008; 37 (3):201-215 - 15.
Bayram S, Bayram NE, Gercek YC, Aydogan MN. Chemical analysis and antimicrobial effect of propolis from Hakkari province of Turkey against some pathogenic microorganisms. European Journal of Biology. 2017; 76 (2):74-78 - 16.
Castaldo S, Capasso F. Propolis an old remedy used in modern medicine. Fitoterapia. 2002; 73 :51-56 - 17.
Silici S. Honeybee products and therapy. Turkish Journal of Agriculture-Food and Science Technology (TURJAF). 2019; 7 (9):1249-1262 - 18.
Bankova VS, Castro DLS, Marcucci MC. Propolis: Recent advances in chemistry and plant origin. Apidologie. 2000; 31 :3-15 - 19.
Przbylek I, Karpinski TM. Antibacterial properties of propolis. Molecules. 2019; 24 :2047. DOI: 10.3390/molecules24112047 - 20.
Pasupuleti VR, Sammugam L, Ramesh N, Honey GSH. propolis and royal jelly: A comprehensive review of their biological actions and health benefits. Oxidative Medicine and Cellular Longevity. 2017:21. DOI: 10.1155/2017/1259510 - 21.
Popova MP, Bankova VS, Bogdanov S, Tsvetkova I, Naydenski C, Marcazzan GL, et al. Chemical characteristics of poplar type propolis of different geographic origin. Apidologie. 2007; 38 :306-311 - 22.
Stepanovic S, Antic N, Dakic I, Svabic-Vlahovic S. In vitro antimicrobial activity of propolis and synergism between propolis and antimicrobial drugs. Microbiological Research. 2003; 158 :353-357 - 23.
AL-Ani I, Zimmermann S, Reichling J, Wink M. Antimicrobial activities of European propolis collected from various geographic origins alone and in combination with antibiotics. Medicine. 2018; 5 (2):1-17 - 24.
Kedzia B. Pochodzenie propolisu w’swietle teori i bada’n naukowych. The origin of propolis in the theories and scientific research. Herba Polonica. 2008; 54 :179-186 - 25.
Zabaiou N, Fouache A, Trousson A, Baron S, Zellagui A, Lahouel M, et al. Biological properties of propolis extracts: Something new from an ancient product. Chemistry and Physics of Lipids. 2017; 207 :214-222 - 26.
Bufalo MC, Candeias MG, Sforcin JM. In vitro cytotoxic effect of Brazilian green propolis on human laryngeal epidermoid carcinoma (HEp-2) cells. Evidence-Based Complementary Alternative Medicine (eCAM). 2009; 6 (4):483-487 - 27.
Banskota AH, Nagaoka T, Sumioka LY, Tezuka Y, Awale S, Midorikawa K, et al. Antiproliferative activity of the Netherlands propolis and its active principles in cancer cell lines. Journal of Ethnopharmacology. 2002; 80 :67-73 - 28.
Orsolic N, Terzic S, Mihaljevic Z, Sver L, Basic I. Effect of local administration of propolis and its polyphenolic compounds on tumor formation and growth. Biological & Pharmaceutical Bulletin. 2005; 28 (10):1928-1933 - 29.
Demestre M, Messerli SM, Celli N, Shahhossini M, Kluwe L, Mautner V, et al. CAPE (Caffeik Acid Phenethyl Ester)-based propolis extract (Bio 30) suppresses the growth of human Neurofibromatosis (NF) tumor xenografts in mice. Phytotherapy Research. 2009; 23 :226-230 - 30.
Kartal M, Yıldız S, Kaya S, Kurucu S, Topçu G. Antimicrobial activity of propolis samples from two different regions of Anatolia. Journal of Ethnopharmacology. 2003; 86 :69-73 - 31.
Tawata S, Taira S, Kobamoto N, Zhu J, Ishihara M, Toyama S. Synthesis and antifungal activity of cinnamic acid esters. Biotechnology and Biochemistry. 1996; 60 :909-910 - 32.
Duran GG. Investigation of antibacterial, antifungal, and Leishmaniacidal effects of propolis in vitro conditions. [Master Thesis], Hatay, Turkey: Mustafa Kemal University, Institute of ScienceTechnology, 2007 - 33.
Hegazi AG, Abd El Hady FK, Abd Allah FAM. Chemical composition and antimicrobial activity of European propolis. Zeitschrift für Naturforschung. 2000; 55 :70-75 - 34.
Pietta PG, Gardana C, Pietta AM. Analytical methods for quality control of propolis. Fitoterapia. 2002; 73 (1):S7-S20 - 35.
Cunha IBS, Sawaya ACHF, Caetano FM, Shimizu MT, Marcucci MC, Drezza FT, et al. Factors that influence the yield and composition of Brazilian propolis extracts. Journal of the Brazilian Chemical Society. 2004; 15 (6):964-970 - 36.
Bakkaloglu Z, Arici M. Effect of propolis extraction with different solvents on total phenolic content, antioxidant capacity and antimicrobial activity. Akademik Gıda. 2019; 17 (4):538-545 - 37.
Popova M, Silici S, Kaftanoglu O, Bankova V. Antibacterial activity of Turkish propolis and its qualitative and quantitative chemical composition. Phytomedicine. 2005; 12 (3):221-228 - 38.
Velikova M, Bankova V, Sorkun K, Popov S, Kujumgiev A. Chemical and biological activity of propolis from Turkish and Bulgarian origin. Mellifera. 2001; 1 :57-59 - 39.
Mohammadzadeh S, Shariatpanahi M, Hamedi M, Ahmadkhaniha R, Samadi N, Ostad SN. Chemical composition, oral toxicity and antimicrobial activity Iranian propolis. Food Chemistry. 2007; 103 :1097-1103 - 40.
Yaghoubi MJ, Ghorbani GH, Soleimanian Zad S, Satari R. Antimicrobial activity of Iranian propolis and its chemical composition. DARU. 2007; 15 (1):45-48 - 41.
Gharib AA, Omnia YAE, Taha M. Antimicrobial activity of propolis against some bacteria and fungi. The Zagazig Veterinary Journal. 2013; 41 (1):81-97 - 42.
Chamandi G, Olama Z, Holail H. Antimicrobial effect of propolis from different geographic origins in Lebanon. International Journal of Current Microbiology and Applied Sciences. 2015; 4 (4):328-342 - 43.
Moncla BJ, Guevara PW, Wallace JA, Marcucci MC, Nor JE, Bretz WA. The inhibitory activity of typified propolis against Enterococcus species. Zeitschrift für Naturforschung. 2012;67 :249-256 - 44.
Kumazawa S, Hayashi K, Kajiya K, Ishii T, Hamasaka T, Nakayama T. Studies of the contituents of Uruguayan propolis. Journal of Agricultural and Food Chemistry. 2002; 50 :4777-4782 - 45.
Hamasaka T, Kumazawa S, Fujimoto T, Nakayama T. Antioxydant activity and constituents of propolis collected in various areas of Japan. Food Science and Technology Research. 2004; 10 (1):86-92 - 46.
Shehu A, Ismail S, Rohin MAK, Harun A, Aziz AA, Haque M. Antifungal properties of Malaysian tualang honey and stingless bee propolis against Candida albicans andCryptococcus neoformans . Journal of Applied Pharmaceutical Science. 2016;6 (2):44-50 - 47.
Montero JC, Mori GG. Assessment of ion diffusion from a calcium hydroxidepropolis paste through dentin. Brazilian Oral Research. 2012; 26 (4):318-322 - 48.
Farnesi AP, Aquino-Ferreira R, De Jong D, Bastos JK, Soares AE. Effects of stingless bee and honey bee propolis on four species of bacteria. Genetics and Molecular Research. 2009; 8 (2):635-640 - 49.
Mello AM, Gomez RT, Lara SR, Silva LG, Alves JB, Cortes ME, et al. The effect of Brazilian propolis on the germ tube formation and cell wall of Candida albicans . Pharmacology. 2006;3 :352-358 - 50.
Santos VR, Pimenta FJGS, Aguiar MCF, do Carmo MAV, Naves MD, Mesquita RA. Oral candidiasis treatment with Brazilian ethanol propolis extract. Phytotherapy Research. 2005; 19 :652-654 - 51.
Ota C, Unterkircher C, Fantinato V, Shimizu MT. Antifungal activity of propolis on different species of Candida . Mycoses. 2001;44 :375-378 - 52.
Yarfani R, Khosravi AR, Shokri H. The antifungal activity of Iranian propolis samples against fluconazole-resistant Candida albicans strains isolated from HIV+ patients with oropharyngeal candidiasis. Journal of ApiProduct and ApiMedical Science. 2010;2 :161-166 - 53.
Oliveira ACP, Shinobu CS, LonghiniR FSL, Svidzinski TIE. Antifungal activity of propolis extract against yeast isolated from onychomycosis lesions. Memórias do Instituto Oswaldo Cruz. 2006; 101 (5):493-497 - 54.
Kartal M, Kaya S, Kurucu S. GC-MS analysis of propolis samples from two different regions of Turkey. Zeitschrift für Naturforschung. 2002; 57 :905-909 - 55.
Sorkun K, Süer B, Salih B. Determination of chemical composition of Turkish propolis. Zeitschrift für Naturforschung. 2001; 56c :666-668 - 56.
Silici S, Kutluca S. Chemical composition and antibacterial activity of propolis collected by three different races of honeybees in the same region. Journal of Ethnopharmacology. 2005; 99 :69-73 - 57.
Katircioglu H, Mercan N. Antimicrobial activity and chemical compositions of Turkish propolis from different region. African Journal of Biotechnology. 2006; 5 (11):1151-1153 - 58.
Temiz A, Sener A, Ozkok Tuylu A, Sorkun K, Salih B. Antibacterial activity of bee propolis samples from different geographical regions of Turkey against two foodborne pathogens, Salmonella enteritidis andListeria monocytogenes . Turkish Journal of Biology. 2011;35 :503-511 - 59.
Ozcan M. Antifungal properties of propolis. Grasas y Aceites. 1999; 50 (5):395-398 - 60.
Ozcan M, Ceylan A, Unver A, Yetişir R. Antifungal effect of polen and propolis extracts collected from different regions of Turkey. Uludağ Arıcılık Derg. 2003; 3 :33-36 - 61.
Koc AN, Silici S, Ayangil D, Ferahbas A, Cankaya S. Comparison of in vitro activities of antifungal drugs and ethanolic extract of propolis against Trichophyton rubrum andT. mentagrophytes by using a microdilution assay. Mycoses. 2005;48 :205-210 - 62.
OzbilgeH KEG, Albayrak S, Silici S. Anti-leishmanial activities of ethanolic extract of Kayseri propolis. African Journal of Microbiology Research. 2010; 4 (7):556-560 - 63.
Duran N, Muz M, Culha G, Duran G, Ozer B. GC-MS analysis and antileishmanial activities of two Turkish propolis type. Parasitology Research. 2011; 108 (1):95-105 - 64.
Kanbur M, Eraslan G, Silici S. Antioxidant effect of propolis against exposure to propetamphos in rats. Ecotoxicology and Environmental Safety. 2009; 72 (3):909-915 - 65.
Seleem D, Pardi V, Murata RM. Review of flavonoids: A diverse group of natural compounds with anti- Candida albicans activity in vitro. Archives of Oral Biology. 2017;76 :73-83 - 66.
Herrera CI, Alvear M, Barrientos I, Montenegro G, Salazar IA. The antifungal effect of six commerical extracts of Chilean propolis on Candida spp. Ciencia e Investigación Agraria. 2010;37 :75-84 - 67.
Mulaudzi RB, Ndhlala AR, Kulkarni MG, Van Staden J. Pharmacological properties and protein binding capacity of phenolic extracts of some Venda medicinal plants used against cough and fever. Journal of Ethnopharmacology. 2012; 143 :185-193 - 68.
Serpa R, Franca EJ, Furlaneto-Maia L, Andrade CG, Diniz A, Furlaneto MC. In vitro antifungal activity of the flavonoid baicalein against Candida species. Journal of Medical Microbiology. 2012;61 :1704-1708 - 69.
Dalleau S, Cateau E, Berges T, Berjeaud JM, Imbert C. In vitro activity of terpenes against Candida biofilms. International Journal of Antimicrobial Agents. 2008; 31 :572-576 - 70.
Nobile CJ, Joshson AD. Candida albicans biofilms and human disease. Annual Review of Microbiology. 2015;69 (1):71-92 - 71.
Bisvas C, Chen SCA, Halliday C, Martinez E, Rocket RJ, Wang Q , et al. Whole genom sequencing of Candida glabrata for detection of markers of antifungal drug resistance, e5674. Journal of Visualized Experiments. 2017;130 - 72.
Fernandez-Calderon MC, Hernandez-Gonzales L, Gomez-Navia C, Blanco-Blanco MT, Sanchez-Silos R, Lucio L, et al. Antifungal and anti-biofilm activity of a new Spanish extract of propolis against C. glabrata . BMC Complementary Medicine and Therapies. 2021;21 :147 - 73.
Capoci IRG, Bonfim-Mendonca PS, Arita GS, Pereira RRA, Consolaro MEL, Bruschi ML, et al. Propolis is an efficient fungicide and inhibitor of biofilm production by vaginal Candida albicans . Evidence-Based Complementary and Alternative Medicine. 2015, 2015:287693. DOI: 10.1155/2015/287693 - 74.
Freires IA, Queiroz VCPP, Furletti VF, Ikegaki M, de Alencar SM, Duarte MCT, et al. Chemical composition and antifungal potential of Brazilian propolis against Candida spp. The Journal of Medical Mycology. 2016;26 :122-132 - 75.
Iadnut A, Mamoon K, Tammasit P, Pawichai S, Tima S, Preechasuth K, et al. In vitro antifungal and antivirulence activities of biologically synthesized ethanolic extract of propolis-loaded PLGA nanoparticles against Candida albicans . Evidence Based Complementary and Alternative Medicine. 2019, 2019:3715481. DOI: 10.1155/2019/3715481