Brazilian Red Propolis: Extracts Production, Physicochemical Characterization, and Cytotoxicity Profile for Antitumor Activity.

Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity and high cytotoxic profile from red propolis, in this work, we proposed a new solvent accelerated extraction method. A complete 23 factorial design was carried out to evaluate the influence of the independent variables or factors (e.g., temperature, number of cycles, and extraction time) on the dependent variable or response (i.e., yield of production). The extracts were analyzed by gas chromatography coupled with mass spectrometry for the identification of chemical compounds. Gas chromatography analysis revealed the presence of hydrocarbons, alcohols, ketones, ethers, and terpenes, such as lupeol, lupenone, and lupeol acetate, in most of the obtained extracts. To evaluate the cytotoxicity profile of the obtained bioactives, the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide colorimetric assay was performed in different tumor cell lines (HCT116 and PC3). The results show that the extract obtained from 70 °C and one cycle of extraction of 10 min exhibited the highest cytotoxic activity against the tested cell lines. The highest yield, however, did not indicate the highest cytotoxic activity, but the optimal extraction conditions were indeed dependent on the temperature (i.e., 70 °C).

Innovative nanocompounds for cutaneous administration of classical antifungal drugs: a systematic review.

Nanomedicine manipulates materials at atomic, molecular, and supramolecular scale, with at least one dimension within the nanometer range, for biomedical applications. The resulting nanoparticles have been consistently shown beneficial effects for antifungal drugs delivery, overcoming the problems of low bioavailability and high toxicity of these drugs. Due to their unique features, namely the small mean particle size, nanoparticles contribute to the enhanced drug absorption and uptake by the target cells, potentiating the therapeutic drug effect. The topical route is desirable due to the adverse effects arising from oral administration. This review provides a comprehensive analysis of the use of nano compounds for the current treatment of topical fungal infections. A special emphasis is given to the employment of lipid nanoparticles, due to their recognized efficacy, versatility, and biocompatibility, attracting the major attention as novel topical nanocompounds used for the administration of antifungal drugs.

Antioxidant, antimicrobial, antiparasitic, and cytotoxic properties of various Brazilian propolis extracts.

Propolis is known for its biological properties and its preparations have been continuously investigated in an attempt to solve the problem of their standardization, an issue that limits the use of propolis in food and pharmaceutical industries. The aim of this study was to evaluate in vitro antioxidant, antimicrobial, antiparasitic, and cytotoxic effects of extracts of red, green, and brown propolis from different regions of Brazil, obtained by ethanolic and supercritical extraction methods. We found that propolis extracts obtained by both these methods showed concentration-dependent antioxidant activity. The extracts obtained by ethanolic extraction showed higher antioxidant activity than that shown by the extracts obtained by supercritical extraction. Ethanolic extracts of red propolis exhibited up to 98% of the maximum antioxidant activity at the highest extract concentration. Red propolis extracts obtained by ethanolic and supercritical methods showed the highest levels of antimicrobial activity against several bacteria. Most extracts demonstrated antimicrobial activity against Staphylococcus aureus. None of the extracts analyzed showed activity against Escherichia coli or Candida albicans. An inhibitory effect of all tested ethanolic extracts on the growth of Trypanosoma cruzi Y strain epimastigotes was observed in the first 24 h. However, after 96 h, a persistent inhibitory effect was detected only for red propolis samples. Only ethanolic extracts of red propolis samples R01Et.B2 and R02Et.B2 showed a cytotoxic effect against all four cancer cell lines tested (HL-60, HCT-116, OVCAR-8, and SF-295), indicating that red propolis extracts have great cytotoxic potential. The biological effects of ethanolic extracts of red propolis revealed in the present study suggest that red propolis can be a potential alternative therapeutic treatment against Chagas disease and some types of cancer, although high activity of red propolis in vitro needs to be confirmed by future in vivo investigations.

In Vivo Anti-Tumor Activity and Toxicological Evaluations of Perillaldehyde 8,9-Epoxide, a Derivative of Perillyl Alcohol.

Recent studies have revealed the high cytotoxicity of p-menthane derivatives against human tumor cells. In this study, the substance perillaldehyde 8,9-epoxide, a p-menthane class derivative obtained from (S)-(-)-perillyl alcohol, was selected in order to assess antitumor activity against experimental sarcoma 180 tumors. Toxicological effects related to the liver, spleen, kidneys and hematology were evaluated in mice submitted to treatment. The tumor growth inhibition rate was 38.4%, 58.7%, 35.3%, 45.4% and 68.1% at doses of 100 and 200 mg/kg/day for perillaldehyde 8,9-epoxide, perillyl alcohol and 25 mg/kg/day for 5-FU intraperitoneal treatments, respectively. No toxicologically significant effect was found in liver and kidney parameters analyzed in Sarcoma 180-inoculated mice treated with perillaldehyde 8,9-epoxide. Histopathological analyses of the liver, spleen, and kidneys were free from any morphological changes in the organs of the animals treated with perillaldehyde 8,9-epoxide. In conclusion, the data suggest that perillaldehyde 8,9-epoxide possesses significant antitumor activity without systemic toxicity for the tested parameters. By comparison, there was no statistical difference for the antitumor activity between perillaldehyde 8,9-epoxide and perillyl alcohol.

Evaluation of the cytotoxicity of structurally correlated p-menthane derivatives.

Compounds isolated from essential oils play an important role in the prevention and treatment of cancer. Monoterpenes are natural products, and the principal constituents of many essential oils. The aim of this study was to investigate the cytotoxic potential of p-menthane derivatives. Additionally, analogues of perillyl alcohol, a monoterpene with known anticancer activity, were evaluated to identify the molecular characteristics which contribute to their cytotoxicity, which was tested against OVCAR-8, HCT-116, and SF-295 human tumor cell lines, using the MTT assay. The results of this study showed that (-)-perillaldehyde 8,9-epoxide exhibited the highest percentage inhibition of cell proliferation (GI = 96.32%-99.89%). Perillyl alcohol exhibited high cytotoxic activity (90.92%-95.82%), while (+)-limonene 1,2-epoxide (GI = 58.48%-93.10%), (-)-perillaldehyde (GI = 59.28%-83.03%), and (-)-8-hydroxycarvotanacetone (GI = 61.59%-94.01%) showed intermediate activity. All of the compounds tested were less cytotoxic than perillyl alcohol, except (-)-perillaldehyde 8,9-epoxide (IC50 = 1.75-1.03 µL/mg). In general, replacement of C-C double bonds by epoxide groups in addition to the aldehyde group increases cytotoxicity. Furthermore, stereochemistry seems to play an important role in cytotoxicity. We have demonstrated the cytotoxic influence of chemical substituents on the p-menthane structure, and analogues of perillyl alcohol.