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| Author(s): |
Bruno Dias Nani
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba |
| Defense date: | 2020-02-17 |
| Examining board members: |
Pedro Luiz Rosalen;
Masaharu Ikegaki;
Patricia Correa Dias;
Karina Cogo Müller;
Antônio Pedro Ricomini Filho
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| Advisor: | Pedro Luiz Rosalen; Marcelo Franchin |
| Abstract | |
Brazilian organic propolis (BOP) is produced in the Brazilian Atlantic Rainforest in the states of Santa Catarina and Paraná. BOP is produced and internationally certified organically and can be grouped into 7 different chemical profiles with antibacterial and antioxidant activities. Among these profiles, BOP profile 6 (PO6) is hightlighted as the only BOP profile with anti-inflammatory activity. Therefire, this research aimed to (1) elucidate the anti-inflammatory mechanisms of action of BOP6; (2) to evaluate BOP6 antifungal activities; (3) to identify potentially bioactive molecules from BOP6; and (4) to verify the biological activities and toxicity of gibberellins (class of terpenoids identified in BOP6). The results showed that the crude PO6 extract has a potent anti-inflammatory activity, reducing the activation of NF-kB, the release of TNF-'alfa' and neutrophil migration. We also showed that the crude extract of BOP6 has antifungal activity in vitro against the species Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, and Candida parapsisolis (MIC and CFM values less than 200 µg / mL; antibiofilm activity in concentrations 10 and 100 times the MIC value, and reducing the adhesion of Candida species to human keratinocytes at concentrations lower than the MIC values). Our results also showed that antifungal doses of BOP6 have low toxicity in an in vivo model with Galleria mellonella larvae. The compounds gibberiline A7, A9 and A20; cafeoiltartaric acid, 3,4-dicafeoiltartaric acid and quercetin were identified at BOP6 by the Precise Mass Liquid Chromatography technique. This was the first report of the presence of gibberellins in propolis samples. Gibberilins A4 and A7 (GA4 and GA7) have distinct anti-inflammatory and antifungal activities: GA4 reduces the activation of NF-kB in macrophages and has no antifungal activity; while GA7 has antifungal activity against the species C. albicans (MIC value of 94 mM, MFC value of 188 mM and antibiofilm activity at a concentration of 100 times the MIC value), but it does not have anti-inflammatory activity. Both GA4 and GA7 have free radical scavenging antioxidant activity against ROO¿ free radical and low toxic profile in the G. mellonella model. Thus, we conclude that: (1) BOP6 has a potent anti-inflammatory activity through the reduction of NF-kB activation; TNF-'alfa' release and neutrophil migration; (2) BOP6 has a potent antifungal activity against the most prevalent species of Candida; (3) the molecules gibberillins A7, A9 and A20; cafeoiltartaric acid, 3,4-tipfeoiltartaric acid and quercetin may be responsible for such biological effects; and (4) GA4 has anti-inflammatory activity, reducing the activation of NF-kB without antifungal activity; whereas GA7 has anti-fungal activity against C. albicans, without showing anti-inflammatory activity; both GA have antioxidant activity against the peroxyl radical and low toxic profile. Our results show that BOP6 is a source of bioactive molecules with great potential, in addition to being a natural product that can be used in the prevention of inflammatory, fungal and oxidative diseases and that the class of gibberillins can be responsible for these effects (AU) | |
| FAPESP's process: | 15/26864-7 - Bioprospection of active compounds from organic propolis with activity on neutrophil migration in inflammatory process. |
| Grantee: | Bruno Dias Nani |
| Support Opportunities: | Scholarships in Brazil - Doctorate |