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Development of a Benzophenone-Free Red Propolis Extract and Evaluation of Its Efficacy against Colon Carcinogenesis

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Squarisi, Iara Silva ; Ribeiro, Victor Pena ; Ribeiro, Arthur Barcelos ; de Souza, Leticia Teixeira Marcos ; Junqueira, Marcela de Melo ; de Oliveira, Katia Mara ; Hayot, Gaelle ; Dickmeis, Thomas ; Bastos, Jairo Kenupp ; Veneziani, Rodrigo Cassio Sola ; Ambrosio, Sergio Ricardo ; Tavares, Denise Crispim
Total Authors: 12
Document type: Journal article
Source: PHARMACEUTICALS; v. 17, n. 10, p. 20-pg., 2024-10-01.
Abstract

Background/Objectives: Brazilian red propolis has attracted attention for its pharmacological properties. However, signs of toxicity were recently observed in long-term studies using the hydroalcoholic extract of red propolis (RPHE), likely due to polyprenylated benzophenones. This study aimed to develop a benzophenone-free red propolis extract (BFRP) and validate an HPLC-PDA method to quantify its main constituents: isoliquiritigenin, vestitol, neovestitol, medicarpine, and 7-O-methylvestitol. Methods: BFRP's toxicity was assessed in zebrafish larvae through a vibrational startle response assay (VSRA) and morphological analysis. Genotoxicity was evaluated using the micronucleus test in rodents, and the extract's effects on chemically induced preneoplastic lesions in rat colon were studied. An HPLC-PDA method was used to quantify BFRP's main compounds. Results: BFRP primarily contained vestitol (128.24 +/- 1.01 mu g/mL) along with isoliquiritigenin, medicarpin, neovestitol, and 7-O-methylvestitol. Zebrafish larvae exposed to 40 mu g/mL of BFRP exhibited toxicity, higher than the 10 mu g/mL for RPHE, though no morphological differences were found. Fluorescent staining in the notochord, branchial arches, and mouth was observed in larvae treated with both BFRP and RPHE. No genotoxic or cytotoxic effects were observed up to 2000 mg/kg in rodents, with no impact on hepatotoxicity or nephrotoxicity markers. Chemoprevention studies showed a 41.6% reduction in preneoplastic lesions in rats treated with 6 mg/kg of BFRP. Conclusions: These findings indicate that BFRP is a safe, effective propolis-based extract with potential applications for human health, demonstrating reduced toxicity and chemopreventive properties. (AU)

FAPESP's process: 17/04138-8 - Attainment of chemical, analytical, biological, pharmacological and technological studies to fill the gaps on the development of Brazilian propolis sector
Grantee:Jairo Kenupp Bastos
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 24/02434-2 - International Congress On Natural Products Research 2024
Grantee:Sergio Ricardo Ambrosio
Support Opportunities: Research Grants - Meeting - Abroad
FAPESP's process: 22/00659-1 - In vitro evaluation of the metabolism of the major compounds of Araucaria sp brown propolis
Grantee:Victor Pena Ribeiro
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 18/05080-6 - Multi-user equipment approved in grant 2017/04138-8 for high pressure semipreparative chromatographic system model LC-20AR
Grantee:Sergio Ricardo Ambrosio
Support Opportunities: Multi-user Equipment Program