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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 ± 9), were included in a clinical trial`s phase II study of the patients who had a minimum of 20 sound natural teeth, a mean plaque index of at least 1.5 (PI), and a mean gingival index (GI) of at least 1.0. They were instructed to rinse with 10mL of mouthwash test for 1 minute, immediately after brushing in the morning and at night. After 45 and 90 days using mouthwash, the results showed a significant reduction in plaque and in gingival index when compared to samples obtained in baseline. These reductions were at 24% and 40%, respectively (P <0.5). There were no important side effects in soft and hard tissues of the mouth.

Baseline 45 days 90 days Reduction %
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

Table 8.

Mean scores of Gingival Index (DP) and percent reduction between periods (Pereira et al., 2011) [29].∗ Friedman test (ANOVA) P <.05.

Baseline 45 days 90 days Reduction-%
MGP5% n = 22
0.30 (0.17)		 n = 22
0.08 (0.06)		 n = 21
0.07 (0.03)		 Baseline–45 days
73*		 Baseline–90 days
77*		 45 days–90 days
13 (ns)**

Table 9.

Mean scores of Severity Gengival Index (DP) and percent reduction between periods (Pereira et al., 2011) [29]. *Friedman test (ANOVA) P <.05. ∗∗Not significant.

Baseline 45 days 90 days Reduction-%
MGP5% n = 22
2.39 (0.69)		 n = 22
1.77 (0.61)		 n = 21
1.82 (0.62)		 Baseline–45 days
26*		 Baseline–90 days
24*		 45 days–90 days∗
______

Table 10.

Mean scores of Plaque Index (DP) and percent reduction between periods (Pereira et al., 2011) [29].∗Friedman test (ANOVA) P <.05.

Baseline 45 days 90 days Reduction-%
MGP5% n = 22
0.44 (0.19)
 n = 22
0.26 (0.14)		 n = 21
0.26 (0.15)		 Baseline–45 days
41*		 Baseline–90 days
41*		 45 days–90 days
____

Table 11.

Mean scores of Severity Plaque Index (DP) and percent between periods (Pereira et al., 2011) [29].∗ Friedman test (ANOVA) P <.05.

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 Candida albicans strains collected from HIV-seropositive and HIV-seronegative Brazilian patients with oral candidiasis. No significant difference was observed between Nystatin and EPE. But significant differences were observed between EPE and other antifungals. C. albicans showed resistance to antifungal agents. This fact suggests commercial EPE could be an alternative medicine for candidosis treatment from HIV-positive patients (Figure 3) [143]. Brazilian commercial ethanol propolis extract, also formulated to ensure physical and chemical stability, was found to inhibit oral candidiasis in 12 denture-bearing patients with prosthesis stomatitis candidiasis association is show in Table 12 and Figure 4 [144]. Also, denture stomatitis presents as a chronic disease in denture-bearing patients, especially under maxillary prosthesis. Despite the existence of a great number of antifungal agents, treatment failure is observed frequently. So, the clinical efficacy of a Brazilian propolis gel formulation in patients diagnosed with denture stomatitis was evaluated. Thirty complete-denture wearers with denture stomatitis were enrolled in this pilot study. At baseline, clinical evaluation was performed by a single clinician and instructions for denture hygiene provided. Fifteen patients received Daktarin® (Miconazole gel) and 15 received Brazilian propolis gel. All patients were recommended to apply the product four times a day during one week. Clinical evaluation was repeated by the same clinician after treatment. All patients treated with Brazilian propolis gel and Daktarin® had complete clinical remission of palatal candidiasis edema and erythema. [77]. Noronha [31] found the efficacy of a Brazilian green propolis mucoadhesive gel (BPGg) in preventing and treating the oral mucositis and candidiasis in patients harboring malignant tumors and receiving radiotherapy. All patients who used the gel applied 24 hours before the first radiotherapy session, three times a day, during the whole period(six weeks) of radiotherapy, did not develop mucositis and candidosis over the entire period of radiotherapy.

Figure 2.

Periodontitis treatment with mucoadhesive green propolis gel. A) Evidencing of dental plaque with basic fuchsin. B) Confirmation of insertion loss and presence of periodontal pockets with periodontal probe. C) Applying mucoadhesive green propolis gel intra-periodontal pocket. D) Clinical aspect of the periodontium after treatment with gel containing propolis (Cairo do Amaral et al. [142].

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].

Figure 3.

Inhibition zones of in vitro culture of Candida albicans collected from HIV-positive patients exposed to Ethanol Propolis Extract (EPE= P), and antifungal agents: CL= clotrimazole; FL= fluconazole; EC= Econazole; NY =Nystatin; AL= Alcohol; DW= Destiled water. (Martins et al., 2002) [143].

Figure 4.

Clinical aspects of oral candidosis in patients with Total Removable Dental Prothesis (TRDP). A) Before propolis use. B) After propolis use. Source: Prof. Vagner Santos archives (2005) [146].

Patient Age (years) Race Gender Prosthesis Local lesions Antifungal agent Result
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 ++

Table 12.

Clinical aspects of patients with oral candidiasis from Clinic of Semiology and Pathology of Dentistry School UFMG participating in this study and Results of in vivo patients treatment of oral candidiasis with 20% Brazilian green ethanol propolis extract (EPE) and Nystatin (Nys). Use posology: 4 time/day for 7 days, topic application in local lesion and prosthesis surface F, female; M, male; TRDP, total removable dental prosthesis; PRDP, partial removable dental prosthesis; B, black; W, white. (Santos et al., 2005) [146]