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

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICALS; v. 17, n. 10, p. 20-pg., 2024-10-01.

Resumo

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)

• Processo FAPESP: 17/04138-8 - Realização de estudos químicos, analíticos, biológicos, farmacológicos e tecnológicos para preenchimento das lacunas no desenvolvimento do setor de própolis brasileiro
• Beneficiário: Jairo Kenupp Bastos
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 24/02434-2 - International Congress On Natural Products Research 2024
• Beneficiário: Sergio Ricardo Ambrosio
• Modalidade de apoio: Auxílio à Pesquisa - Reunião - Exterior
• Processo FAPESP: 22/00659-1 - Avaliação in vitro do metabolismo dos compostos majoritários da própolis marrom de Araucaria sp
• Beneficiário: Victor Pena Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/05080-6 - EMU concedido no processo 2017/04138-8 para sistema de cromatografia líquida de alta pressão semipreparativo modelo LC-20AR
• Beneficiário: Sergio Ricardo Ambrosio
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários