无二苯甲酮红蜂胶提取物的研制及其对结肠癌发生的防治效果评估

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

作者信息

Squarisi Iara Silva, Ribeiro Victor Pena, Ribeiro Arthur Barcelos, de Souza Letícia Teixeira Marcos, Junqueira Marcela de Melo, de Oliveira Kátia Mara, Hayot Gaelle, Dickmeis Thomas, Bastos Jairo Kenupp, Veneziani Rodrigo Cassio Sola, Ambrósio Sérgio Ricardo, Tavares Denise Crispim

机构信息

Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca 14404-600, SP, Brazil.

Institute of Biological and Chemical Systems-Biological Information Processing-Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany.

出版信息

Pharmaceuticals (Basel). 2024 Oct 8;17(10):1340. doi: 10.3390/ph17101340.

DOI:10.3390/ph17101340

PMID:39458981

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11510570/

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--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 μg/mL) along with isoliquiritigenin, medicarpin, neovestitol, and 7-O-methylvestitol. Zebrafish larvae exposed to 40 µg/mL of BFRP exhibited toxicity, higher than the 10 µg/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.

摘要

背景/目的：巴西红蜂胶因其药理特性而备受关注。然而，最近在使用红蜂胶水醇提取物（RPHE）的长期研究中观察到毒性迹象，这可能归因于聚异戊烯化二苯甲酮。本研究旨在开发一种不含二苯甲酮的红蜂胶提取物（BFRP），并验证一种高效液相色谱 - 光电二极管阵列检测法（HPLC - PDA）来定量其主要成分：异甘草素、紫铆醇、新紫铆醇、美迪紫檀素和7 - O - 甲基紫铆醇。

方法

通过振动惊吓反应试验（VSRA）和形态学分析评估BFRP对斑马鱼幼体的毒性。使用啮齿动物微核试验评估遗传毒性，并研究该提取物对大鼠结肠化学诱导的癌前病变的影响。采用HPLC - PDA方法定量BFRP的主要化合物。

结果

BFRP主要含有紫铆醇（128.24 ± 1.01 μg/mL），以及异甘草素、美迪紫檀素、新紫铆醇和7 - O - 甲基紫铆醇。暴露于40 μg/mL BFRP的斑马鱼幼体表现出毒性，高于RPHE的10 μg/mL，但未发现形态学差异。在用BFRP和RPHE处理的幼体中均观察到脊索、鳃弓和口部的荧光染色。在啮齿动物中，高达2000 mg/kg未观察到遗传毒性或细胞毒性作用，对肝毒性或肾毒性标志物无影响。化学预防研究表明，用6 mg/kg BFRP处理的大鼠癌前病变减少了41.6%。