Chemical constituents markers of Brazilian green propolis sample
1. Introduction
Bees are arthropods of Hymenoptera order and are classified into two groups based on their type of life: solitary and social life. Propolis is produced by bees that live socially, from the harvesting of products derived from plants and used to seal and protect the hive against intruders and natural phenomena [1]. Propolis term derives from the Greek Pro, "opposite, the entry" and polis, "city or community" [2,3]. Propolis is a natural substance collected by
Interest in the pharmacological action of natural products has grown and found significant popular acceptance. Among these products, propolis has been highlighted due to its applicability in the food industry and cosmetics, to be used as the active ingredient in several products, among which include toothpastes and skin lotions [13]. Also available in the form of a capsule (pure or combined), extract (hydroalcoholic or glycolic acid), mouthwash (combined with melissa, sage, mallow and / or rosemary), lozenges, creams and powders (for use in or gargling internal use, once dissolved in water) [2].
Regarding the ethnobotanical aspect, propolis is one of the few "natural remedies" that continue to be used for a long period by different civilizations [14]. Propolis is widely used in popular medicine, especially in communities with inadequate public health conditions[15]. It was noticed that it can be more effective and less toxic than certain compounds. Significant decrease in H₂O₂-induced DNA damage in cultures treated with propolis demonstrated antioxidant activity of phenolic components found in propolis may contribute to reduce the DNA damage induced by H₂O₂ [16].
2. History
Propolis is a natural remedy that has been used extensively since antiquity. The Egyptians, who knew very well the anti-putrefactive properties of propolis, used it for embalming [17]. It was recognized for its medicinal properties by Greek and Roman physicians, such as Aristotle, Dioscorides, Pliny and Galen. The drug was used as an antiseptic and healing in the treatment of wounds and as a mouthwash, and its use in the Middle Ages perpetuated among Arab doctors [2]. Also, it was widely used in the form of ointment and cream in the treatment of wounds in battle field, because of their healing effect. This healing propolis property known as "Balm of Gilead," is also mentioned in the Holy Bible [18]. From the pharmacological point of view, propolis has been used as solid; in an ointment based on vaseline, lanolin, olive oil or butter, and in the form of alcoholic extract and hydroalcoholic solution. The proportion propolis/carrier may vary, in order to obtain bacteriostatic or bactericidal results [19]. In the 1980s and 1990s, a great number of publications occurred worldwide, highlighting Japan in number of published papers followed by Brazil and Bulgaria [6]. In Dentistry, there are studies investigating the pharmacological activity of propolissome situations, such as gingivitis, periodontitis, oral ulcers, pulp mummification in dogs' teeth and dental plaque and caries in rats [19]. Also, it has been used in dressings of pre and post-surgical treatment, oral candididosis, oral herpes virouses and oral hygiene. There was also the investigation of antiseptic and healing properties of propolis in subjects admitted to various hospitals and the results were extremely positive [20]. Thus, this natural product revealed great interest for the treatment of oral diseases [21]. Internationally, the first licensed commercial product containing propolis was registered in Romania in 1965. Worldwide, in the same period analyzed, it was found a total of 239 commercial licenses. In the 1980s, commercial licenses were predominant in the former USSR and satellite countries. Currently, 43% of commercial licenses are Japanese origin and 6.2% of them are products for dental treatment. In Japan, the scientific productivity reported for propolis increased 660% between the 1980 and 1990 [22]. The global interest in propolis research increased considerably in relation to its various biological properties [23-27]. Another incentive for conducting research on propolis is a high value on the international market, mainly in Japan, where a bottle of ethanol extract is sold at prices ten times higher than that prevailing in Brazil. Brazil is considered the third largest producer of propolis in the world, behind Russia and China only. Japan’s interest for the Brazilian propolis is due to its therapeutic and organoleptic properties, and also the presence of minor amounts of heavy metals and other environmental pollutants [28,29]. In the last thirty years, various studies and scientific research were performed to clarify the medicinal properties attributed to propolis [30,31].
3. Classification / rating
There was an attempt to classify the Brazilian propolis into twelve types according to physical-chemical properties and geographical reports. However, to date, only three types of propolis had their botanical origin identified. The main types of botanical origin are South (three), Northeast (six) and Southeast (twelve), and they were reported as resins from
4. Chemical composition
Table 1 and Table 2 show the chemical markers constituents of green and red Brazilian propolis, respectively, while Table 3 shows the chemical composition of various types of world propolis. The highest concentration of phenolic compounds was obtained using solvents with lower concentrations of ethanol and higher concentrations of crude propolis, but the highest concentration of flavonoids in the extract was obtained with higher concentrations of ethanol in the solvent [11]. Over 300 chemical compounds are described in various propolis origins [22]. Among the chemicals constituents, we can include waxes, resins, balsams, oils and ether, pollen and organic material. The proportion of these substances varies and depends on the place and period of collection [5,37]. The collected propolis in a bee hive, also known as crude propolis, in its basic composition, contains about 50% of plant resins, 30% of beeswax, 10% essential oils, 5% pollen, 5% debris of wood and earth [7,14,6]. Propolis also contains various organic acids, considerable amount of minerals (including, manganese, zinc, calcium, phosphorus, copper), vitamins B1, B2, B6, C and E, acids (nicotinic acid and pantothenic acid) and aminoacids [5,7,11,38]. These constitutive features may vary by region and period of the year [39, 40].
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1 | Coumaric acid | 3.56 |
2 | Cinnamic acid | 1.66 |
3 | Quercetin | 1.38 |
4 | Kaempferol | 1.77 |
5 | Isorhamnetin | 0,91 |
6 | Sakuranetin | 5.57 |
7 | Pinobanskin-3-acetate | 13.92 |
8 | Chrysin | 3.51 |
9 | Galangin | 9.75 |
10 | Kaempferide | 11.60 |
11 | Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) |
82.96 |
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01 | Rutin | 0.7 |
02 | Liquiritigenin | 1.8 |
03 | Daidzein | 0.3 |
04 | Pinobanksin | 1.7 |
05 | Quercetin | 0.5 |
06 | Luteolin | 1.2 |
07 | Dalbergin | 0.4 |
08 | Isoliquiritigenin | 4.8 |
09 | Formononetin | 10.2 |
10 | Pinocembrin | 3.3 |
11 | Pinobanksin-3-acetate | 1.7 |
12 | Biochanin A | 0.5 |
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Fatty and aliphatic acids (24–26%) | Flavonoids (18–20%) | Microelements (0.5–2.0%) | Burdok et al. [7] Maciejewicz et al [43] Park et al. [32] Kumazawa et al.[44] Salatino et al. [3] Ozkul et al.[45] Eremia et al.[46] Machado et al.[47] Vandor-Unlu et al.[48] Wang et al.[49] |
Butanedioic acid (Succinic acid) | Astaxanthin | Aluminum (Al) | |
Propanoic acid (Propionic acid) | Apigenin | Copper (Cu) | |
Decanoic acid (Capric acid) | Chrysin | Magnesium (Mg) | |
Undecanoic acid | Tectochrysin | Zinc (Zn) | |
Malic acid | Pinobanksin | Silicon (Si) | |
D-Arabinoic acid | Squalene | Iron (Fe) | |
Tartaric acid | Pinostrobin chalcone | Manganese (Mn) | |
Gluconic acid | Pinocembrin | Tin (Sn) | |
α-D-Glucopyranuronic | acid Genkwanin | Nickel (Ni) | |
Octadecanoic acid (Stearic acid) | Galangin | Chrome (Cr) | |
β-D-Glucopyranuronic acid | Acacetin | ||
9,12-Octadecadienoic acid | Kaemferide | ||
Tetradecanoic acid | Rhamnocitrin | ||
Pentanedioic acid | 7,4’-dimethoxyflavone | ||
Glutamic acid | 5-hydroxy-4’7-dimethoxyflavone | ||
2,3,4-trihydroxy butyric acid | 5,7-dihydroxy-3,4’dihydroxyflavone | ||
Phosphoric acid | 3,5-dihydroxy-7,4’-dimethoxyflavone | ||
Isoferulic acid | |||
Sugars (15–18%) | Others (21–27%) | ||
Sorbopyranose | Cyclohexanone | ||
D-Erythrotetrofuranose | 3-methyl,antitricyclo undec-3-en 10-one | ||
D-Altrose | Cyclohexane | ||
D-Glucose | Cyclopentene | ||
Arabinopyranose | 5-n-propyl-1,3 dihydroxybenzene | ||
d-Arabinose | Butane | ||
α-D-Galactopyranose | 2(3H)-Furanone | ||
Maltose | L-Proline | ||
α-D-Glucopyranoside | 2-Furanacetaldehyde | ||
D-Fructose | 2,5-is-3-phenyl-7-pyrazolopyrimidine | ||
Aromatic acids (5–10%) | Esters (2–6%) | Cliogoinol methyl derivative | |
Benzoic acid | Caffeic acid phenethyl ester | Fluphenazine | |
Caffeic acid | 4,3-Acetyloxycaffeate | 4,8-Propanoborepinoxadiborole | |
Ferulic acid, | Cinnamic acid | 1,3,8-Trihydroxy-6-methylanthraquinone | |
Cinnamic acid | 3,4 dimethoxy-trimethylsilyl ester | 1-5-oxo-4,4-diphenyl-2-imidazolin-2-yl guanidine | |
3-Methoxy-4-cinnamate | 3,1,2-Azaazoniaboratine/Piperonal | ||
Cinnamic acid | 4 methoxy 3 TMS ester 3-Cyclohexene | ||
2-propenoic acid methyl ester | 1H-Indole | ||
Alcohol and terpens (2–3.3%) 1H- | Vitamins (2–4%) | Indole-3-one | |
Glycerol | A, B1, B2, E, C, PP | 2-Furanacetaldehyde | |
Erythritol | Guanidine | ||
α-Cedrol | 2(3H)Furanone | ||
Xylitol | 1,3,8-trihydroxy-6-meyhylanthraquinone | ||
Germanicol | |||
Stigmast-22-en-3-ol | |||
Pentitol | |||
Ribitol | |||
Vanilethanediol | |||
Bicyclohept-3-en-2-ol | |||
Farneso |
However, the plant determines the chemical composition of propolis [4,39,40]. Today there are various substances known in propolis with distinct chemical structures from following classes: alcohols, aldehydes, aliphatic acids, aliphatic esters, amino acids, aromatic acids, aromatic esters, flavonoids, hydrocarbohydrates esters, ethers, fatty acids, ketones, terpenoids, steroids and sugars [21].The first studies to identify the active elements of propolis were performed in 1911 by researchers in Germany [50]: vanillin, cinnamic acid and alcohol. In the 1970s, [51] succeeded in isolating and identifying eleven elements, especially the most important type flavonoids, mainly flavones, flavonols and flavonones, terpenes, alpha-aceto butilenol and isovanillin. At the same time, [52] it was identified the unsaturated aromatic acids such as caffeic and ferulic acids. In the same decade, Kadakov et al.[53] reported the presence of thirteen amino acids in samples of propolis. The therapeutic effects are attributed to various phenolic compounds whichmake up the green propolis, which are widely distributed in plant kingdom. These flavonoids can be considered the main compounds [7,8], and also some phenolic acids and their esters, phenolic aldehydes, alcohols and ketones [54]. Flavonoids and caffeic acid phenethyl ester (CAPE) are phenolic compounds which have the ability to inhibit the growth and cell division and to increase membrane permeability interfering with microbial cell motility [13]. Despite being the most studied components of propolis, flavonoids are not solely responsible for the pharmacological properties. Several other components have been related to the medicinal properties of propolis [55]. Propolis from Europe and China contains many flavonoids and phenolic acids esters. Flavonoids are present only in small quantities in Brazilian propolis. The major components of propolis of Brazilian origin are terpenoids and ñ-coumarin prenylated acid derivatives [39]. In Southeastern Brazil there is plenty of the botanical species for production of green resin, which is the
5. Therapeutic properties of propolis
Currently, it is known that Brazilian propolis shows several biological activities, such as antimicrobial, antiinflammatory, immunomodulatory, among others [12]. The composition of propolis is very complex. We can observe the following: antibacterial activity, conferred by the presence of flavonoids, aromatic acids and esters in its composition; bactericidal action resulting from the presence of cinnamic acid and coumarin;
5.1. Anti-inflammatory activity
As an anti-inflammatory agent, green propolis is known to inhibit the prostaglandin synthesis, activate the thymus gland, help the immune system by promoting the phagocytic activity, stimulating cellular immunity, and increasing healing effects on epithelial tissue. Additionally, the propolis contains elements such as iron and zinc, which are important for the synthesis of collagen [63,35]. Recently it was reported that Artepillin C has an inhibitory effect on nitric oxide and prostaglandin E2 by modulating NF-êâ using the macrophage cell line RAW 264.7 [64]. The anti-inflammatory activity observed in green propolis seems to be due to the presence of prenylated flavonoids and cinnamic acid. These compounds have inhibitory activity against cyclooxygenase (COX) and lipooxygenase. It also appears that the caffeic acid phenethyl ester (CAPE) has anti-inflammatory activity by inhibiting the release of arachidonic acid from cellular membrane, removing the activities of COX-1 and COX-2 [65, 66]. Propolis also exhibits anti-inflammatory effects against models of acute and chronic inflammation (formaldehyde and adjuvant-induced arthritis, carrageenin and PGE 2, induced paw edema and granuloma pellete cotton). The exact mechanism of anti-inflammatory action of propolis is still unclear [2]. Treatment with 50 µM CAPE significantly reduced the levels of leptin (p<0.05), resistin (p<0.05) and tumor necrosis factor (TNF)-alpha (p<0.05) which are known to aid adipocytokines production in adipocytes. CAPE has inhibitory effects on 3T3-L1 mouse fibroblast differentiation to adipocytes. In 3T3-L1 cells, treatment of CAPE decreased the triglyceride deposition similar to resveratrol, which is known to have an inhibitory effect on 3T3-L1 differentiation to adipocytes. In conclusion, we found that CAPE suppresses the production and secretion of adipocytokines from mature adipocytes in 3T3-L1 cells [67]. The crude hexane and dichloromethane extracts of propolis displayed antiproliferative/cytotoxic activities with IC50 values against the five cancer cell lines ranging from 41.3 to 52.4 μg/ml and from 43.8 to 53.5 μg/ml, respectively. Two main bioactive components were isolated, one cardanol and one cardol, with broadly similar in vitro antiproliferation/cytotoxicity IC(50) values against the five cancer cell lines and the control Hs27 cell line, ranging from 10.8 to 29.3 μg/ml for the cardanol and < 3.13 to 5.97 μg/ml (6.82 - 13.0 μM) for the cardol. Moreover, both compounds induced cytotoxicity and cell death without DNA fragmentation in the cancer cells, but only an antiproliferation response in the the non-transformed human foreskin fibroblast cell line
(Hs27, ATCC No. CRL 1634) used as a comparative control.However, these compounds did not account for the net antiproliferation/cytotoxic activity of the crude extracts suggesting the existence of other potent compounds or synergistic interactions in the propolis extracts. This is the first report that
5.2. Antimicrobial activity
5.2.1. Antibacterial and antifungal activity
Previous studies have shown that green propolis extracts inhibit the
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20-50 | 100-300 | 16.3±0.52 |
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20-50 | 100-300 | 12.3±0.08 |
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20-50 | 100-300 | 15.6±0.50 |
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20-50 | 100-400 | 28.3±0.15 |
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20-50 | 100-400 | 18.6±0.08 |
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20-50 | 100-400 | 12.6±0.57 |
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25-50 | 200-400 | 18.3±1.15 |
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25-50 | 200-400 | 28.6±0.57 |
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20-50 | 200-400 | 17.5±2.50 |
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30-60 | 300- 500 | 14.0±0.00 |
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25-50 | 300-500 | 15.3±1.15 |
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25-50 | 200-400 | 16.3±2.08 |
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30-50 | 200-400 | 14.0±0.00 |
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30-60 | 200-400 | 15.2±0.26 |
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30-60 | 200-400 | 17.3±0.57 |
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30-60 | 200-400 | 14.6±0.57 |
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14.00 | 16.00 | _ | _ |
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14.00 | 16.00 | _ | _ |
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28.00 | _ | 8.00 |
1.00 |
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14.00 | _ | 32.00 | 4.00 |
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1.75 | _ | 32.00 |
4.00 |
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7.00 | _ | - 16.00 |
2.00 |
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3.50 | _ | 8.00 | 1.00 |
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5% | 10% | 15% | 20% | 5% | 10% | 15% | 20% | |||||
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13.33±3.09 | 19.00±2.00 | 19.66±2.08 | 23.33±1.52 | 9.66±1.52 | 15.66±2.58 | 14.33±2.08 | 18.33±1.52 | 14.33±0.57 | 9.33±1.52 | ||
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13.00±1.00 | 17.66±2.08 | 18.66±2.08 | 21.66±0.57 | 9.66±0.57 | 12.33±1.15 | 14.00±1.00 | 15.00±2.00 | 18.33±2.51 | 11.00±1.53 | ||
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12.00±1.00 | 14.66±2.08 | 15.00±2.08 | 21.66±2.51 | 7.33±1.15 | 9.66±2.08 | 11.66±2.08 | 13.66±1.52 | 14.00±1.73 | 10.00±1.00 | ||
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14.66±1.15 | 18.33±0.57 | 21.00±1.00 | 24.00±1.00 | 9.66±0.57 | 11.00±1.00 | 12.66±0.57 | 15.00±1.00 | 9.66±2.08 | 7.66±1.15 | ||
A.a |
14.33±1.52 | 18.00±2.00 | 21.66±2.08 | 25.33±2.08 | 8.66±2.51 | 11.00±2.00 | 14.33±1.52 | 13.66±1.52 | 18.00±2.00 | 12.00±1.00 |
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5% | 10% | 15% | 20% | 5% | 10% | 15% | 20% | |||
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16.33±1.52 | 21.66±1.57 | 23.00±1.00 | 26.00±1.00 | 12.33±1.52 | 17.00±1.00 | 16.66±1.52 | 20.66±0.57 | 12.00±2.00 | 8.66±1.52 |
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16.66±2.51 | 24.33±2.03 | 23.00±2.00 | 26.00±2.00 | 13.33±2.08 | 19.33±0.57 | 17.66±0.57 | 19.00±1.00 | 14.66±1.52 | 10.66±1.52 |
5.2.2. Antiviral activity
There are many reports on the antiviral activity of propolis. In a study performed in Ukraine compared the efficacy of ointment with propolis Canadian ointments acyclovir and placebo (vehicle) in treating subjects with type 2 Herpes applicant. The preparation of propolis containing flavonoids found to be more effective than the other two in wound healing and reduction of local symptoms [98]. The cytotoxic and antiherpetic effect of propolis extracts against HSV-2 was analysed in cell culture, and revealed a moderate cytotoxicity on RC-37 cells. However both propolis extracts exhibited high anti-herpetic activity when viruses were pretreated with these drugs prior to infection. Selectivity indices were determined at 80 and 42.5µg/mL for the aqueous and ethanolic extract, respectively, thus propolis extracts might be suitable for topical therapy in recurrent herpetic infection [99]. Huleihel & Isanu [100] reported potent antiviral activity of propolis against Herpes simplex-1 infection
5.3. Antioxidative activity
The antioxidative activity deserves special interest because propolis could be topically applied successfully to prevent and treat skin damaged [85, 86, 87]. Phenolic compounds found in high concentrations in Brazilian green propolis, including Artepillin C, have a wide range of biological properties including the ability to act as an anti-oxidizing free radicals and nitric oxide radicals and also the ability to interfere with the inflammatory response through inhibition of iNOS and COX-2 activities [88]. Although studies of propolis ethanol extracts are very common, it is reported that the aqueous extract has good antioxidant activity, associated with high content of phenolic compounds [89,90,91, 92]. Some studies have indicated propolis inhibiting superoxide anion formation, which is produced during autoxidation of â-mercaptoethanol [93,2]. The antioxidative activity of propolis and its main phenolic compounds, caffeic acid, p-coumaric acid, ferulic acid, and caffeic acid phenethyl ester, were investigated in yeast
5.4. Antitumoral activity
Several researchers reported the antitumoral property of propolis
5.5. Immunomodulatory activity
The immunomodulatory activity of propolis is one of the most studied areas in conjunction with its anti-inflammatory property [116-120]. The immunomodulatory action of propolis seems to be limited to macrophages, with no influence on the proliferation of lymphocytes [121]. The inhibitory effect of green propolis (5-100µg/mL) on splenocyte proliferation was observed
6. Toxicity
It must be emphasized that propolis has the advantage of being a natural product, with a higher molecular diversity. It has many therapeutic substances compatible with the metabolism of mammals in general, which reduces the possibility of causing adverse reactions to oral tissue as compared to industrial products tested [13]. The aqueous and alcoholic extracts of propolis do not cause irritation to the tissues [17] and are considered relatively toxic [7]. Experimental mouthwash solutions containing propolis showed no significant inhibitory activity of microorganisms as effective as chlorhexidine, but found lower cytotoxicity on human gingival fibroblasts; propolis is relatively non-toxic and studies have exhibited a no-effect level in a mice study of 1400 mg/kg weight/day leading the authors to propose that a safe dose in humans would be 1.4 mg/kg weight/day, or approximately 70 mg/day [63]. On other hand, Pereira et al. [29] demonstrated high effectiveness of mouthwash containing propolis in control of dental plaque and gingivitis in humans and not observed no toxic or side effects in the administration of the rinse during 90 days. Propolis is considered safe in small doses. Therefore, adverse effects are common at doses above 15g/day. The most commonly experienced adverse effects are allergic reactions, as well as irritation of the skin or mucous membranes [129]. Caution should be used in the treatment of individuals with asthma and eczema and nettle rash [2].
7. Standardization
A universal chemical standardization of propolis would be impossible. Therefore, a detailed investigation of its composition, botanical origin and biological properties is significant [6]. It was postulated that different propolis may have different chemical and pharmaceutical properties. In this sense, standardization of propolis is required. Most studies on the chemistry of propolis include those directed to the European propolis composed of
8. Oral clinical studies
Several clinical studies have demonstrated propolis efficacy in clinical trials, but the majority of studies involve topical application [20, 136-138]. The great diversity and the complexicity of chemical components makes difficult to standardize and to research the mechanisms of action. It is known the propolis anti-inflammatory, anti-microbial, analgesic, antioxidant, and antitumorproperties. Recently, some authors have demonstrated the properties of some components, however, one can not consider when using propolis but as a whole. The antimicrobial activity, for example, may be effective when considering the synergism between the components. Moreover, there was always the concern of several authors to develop oral mouthwashes- based propolis to control oral microbiota [138-140]. Koo et al.[141] demonstrated the effect of a mouthrinse containing selected propolis on 3-day dental plaque accumulation and polysaccharide formation and observed the Dental Plaque Index(PI) for the experimental group was 0.78 (0.17), significantly less than for the placebo group, 1.41 (0.14). On other hand, the experimental mouthrinse reduced the PI concentration in dental plaque by 61.7% compared to placebo (p < 0.05). The clinical efficacy of an alcohol-free mouthwash containing 5.0% (W/V) Brazilian green propolis (MGP 5%) for the control of plaque and gingivitis were demonstrated by Pereira et al.[29] (Tables 8, 9, 10, and 11). Twenty five subjects, men and women aging between 18 and 60 years old (35
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MGP5% | N=22 1.17 (0.20) |
N=22 0.64 (0.24) |
N=21 0.70 (0.18) |
Baseline- 45 days 45* |
Baseline- 90 days 40* | 45 days – 90 days |
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MGP5% |
0.30 (0.17) |
0.08 (0.06) |
0.07 (0.03) |
Baseline–45 days 73* |
Baseline–90 days 77* |
45 days–90 days 13 (ns)** |
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MGP5% |
2.39 (0.69) |
1.77 (0.61) |
1.82 (0.62) |
Baseline–45 days 26* |
Baseline–90 days 24* |
45 days–90 days∗ ______ |
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MGP5% |
0.44 (0.19) |
0.26 (0.14) |
0.26 (0.15) |
Baseline–45 days 41* |
Baseline–90 days 41* |
45 days–90 days ____ |
In this study, the MGP 5% showed evidence of its efficacy in reducing PI and GI. However, it is necessary to perform a clinical trial, double-blind, randomized to validate such effectiveness [29]. Regression of 95% gingivitis and suppuration in all the teeth irrigated with Brazilian Green Propolis gel (BGPg), as well as a pocket depths and all treated patients with the BGPg showed periodontitis/gingivitis regression. This result suggest that 10% BGPG used could be used as an adjuvant therapeutic method assigned for the treatment of periodontal disease (Figure 2) [142]. Ethanol Propolis Extract (EPE) inhibited all the
The prevalence of candidosis in denture wearers is as well established as its treatment with antifungal agents (AAs). However, little research has been done regarding the effects of AAs on denture base surfaces. Then, da Silva et al.[150] evaluate the effects of fluconazole (FLU), nystatin (NYS) and propolis orabase gel (PRO) on poly (methyl-methacrylate) (PMMA) surfaces. So, PRO was able to induce changes in PMMA surface properties, such as roughness, which could be related to microbial adhesion [146]. Recurrent aphthous stomatitis (RAS) is a common, painful, and ulcerative disorder of the oral cavity of unknown etiology. No cure exists and medications aim to reduce pain associated with ulcers through topical applications or reduce outbreak frequency with systemic medications, many having serious side effects. Propolis is a bee product used in some cultures as treatment for mouth ulcers. A randomized, double-blind, placebo-controlled study, patients were assigned to take 500 mg of propolis or a placebo capsule daily. Subjects reported a baseline ulcer frequency and were contacted biweekly to record recurrences. Data were analyzed to determine if subjects had a decrease of 50% in outbreak frequency. The data indicated a statistically significant reduction of outbreaks in the propolis group (Fisher's exact test, one sided, p = 0.04). Patients in the propolis group also self-reported a significant improvement in their quality of life (p = 0.03). This study has shown propolis to be effective in decreasing the number of recurrences and improve the quality of life in patients who suffer from RAS [145].
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ISS Hard | 29 | B | F | TRDP | palate/soft palate | Nys | + |
SVCL | 34 | W | F | TRDP | Hard palate | Nys | + |
AFF | 36 | W | M | TRDP | Hard palate | Nys | + |
GMR | 37 | W | M | TRDP | Hard / soft palate | Nys | ++ |
MIC | 39 | B | F | TRDP | Hard palate | NYS | + |
AFS | 71 | B | F | TRDP | Hard palate | Nys | ++ |
EGSM | 29 | W | F | TRDP | Hard /soft palate | EPE | + |
TMS | 31 | B | F | TRDP | Hard palate | EPE | ++ |
LMC | 33 | W | M | TRDP | Hard palate | EPE | + |
HL | 38 | W | M | TRDP/PRDP | Hard palate/ alveolar mucosa | EPE | + |
SFS | 39 | W | F | TRDP | Hard /soft palate | EPE | ++ |
MCTS | 43 | W | M | TRDP/PRDP | Hard palate/ alveolar mucosa | EPE | + |
MJNM | 46 | W | F | TRDP | Hard palate | EPE | ++ |
46 | B | F | TRDP | Hard palate | EPE | + | |
HBS | 48 | B | M | TRDP | Hard palate | EPE | + |
JJAF | 50 | W | F | TRDP | Hard palate | EPE | + |
GRA | 56 | W | F | TRDP | Hard palate | EPE | ++ |
NMBA | 63 | W | F | TRDP | Hard palate | EPE | ++ |
9. Future perspectives
The potential pharmacological activity investigation of natural products, especially antimicrobial activity, has attracted the attention of several researchers. Increase of bacterial resistance to traditional antimicrobial agents and side effects are often seen [147, 28]. Many mouthwashes with alcohol are used as adjuvants in the control of dental plaque and gingivitis, but undesirable side effects are observed, despite its efficacy. This stimulates the research of alternative products, such as the use of toothpastes and mouthwashes based on natural products, because there is the need for prevention and treatment options that are safe, effective and economical. Mouthwash based on herbal extracts and propolis are for sale in the Brazilian and world market, without, however, have undergone clinical studies proving their effectiveness and documenting possible undesirable side effects. Previous studies have demonstrated the efficacy of propolis extracts as an antimicrobial agent useful for dental caries and periodontal pathogens microorganisms in
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Green Propolis extract | Apoptosis and cell propliferation | Giertsen et al, 2011 [153] |
Moronic acid | Epstein-Barr virus suppresion | Chang et al., 2010 [154] |
Polyphenols | Neurological diseases | Farooqui and Farooqui, 2012 [15] |
Red propolis extract | Adipocyte differentiation | Iio et al., 2010 [155] |
Caffeic acid phenethyl ester Cardanol, cardol |
Antitumoral / anticancer, citotoxicity | Chuu et al., 2012 [156] Sawaya et al., 2011 [39] Chan et al., 2012 [152] Watanabe et al., 2011 [159] Teerasripreecha et al, 2012 [68] |
epicatechin, |
Antioxidant | Guimaraes et al., 2012 [95] Guo et al., 2011 [87] Sawaya et al, 2011 [39] |
3-prenyl-4-hydroxycunnamic acid, 2,2-dimethyl-6-carboxyethenyl,2H-1-benzopyran; 3,5-diprenyl-4-hydroxycinnamic acid derivative 4 (DHCA4) 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyran (DCBEN |
Antiparasitic |
Sawaya et al., 2011 [39] Salomao et al., 2008 [160] Salaomao et al., 2011 [161] |
Green, red and brown propolis extracts; Artepillin C; Crysin |
Anti-inflamatory | Marcucci et al., 2000 [11] Ha et al., 2010 [158] Sawaya et al., 2011 [39] Moura et al., 2011 [57] Orsatti et al., 2012 [128] |
Green, Red, Brown propolis extract; p-coumaric acid (PCUM), 3-(4-hydroxy-3-(oxo-butenyl)-phenylacrylic acid (DHCA1); Caffeic acid, caffeoylquinic acid, diterpenic acids, flavonoids | antimicrobial | Martins et al., 2002 [143] Paula et al., 2006 [59]; Santos et al., 2007 [71] Dias et al., 2012 [162]; Mattigatti et al., 2012 [163] Sawaya et al., 2011 [39] Choudhari et al., 2012 [157] |
Acknowledgments
Research Foundation of Minas Gerais State (FAPEMIG), National Council of Scientific and Tecnologic Development (CNPq) for financial support in all of our research group and also for supporting the publication of this chapter. Special thanks to Gustavo Araujo and Rafael Tomaz.References
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