Browsing by Author "Vale, Nuno"
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- Honeybee venom synergistically enhances the cytotoxic effect of CNS drugs IN HT-29 colon and MCF-7 breast cancer cell linesPublication . Duarte, Diana; Falcão, Soraia; El Mehdi, Iouraouine; Vilas-Boas, Miguel; Vale, Nuno5-fluorouracil (5-FU) and doxorubicin (DOX) are potent anti-tumour agents commonly used for colon and breast cancer therapy, respectively. However, their clinical application is limited by their side effects and the development of drug resistance. Honeybee venom is a complex mixture of substances that has been reported to be effective against different cancer cells. Its active compound is melittin, a positively charged amphipathic peptide that interacts with the phospholipids of the cell membrane, forming pores that enable the internalization of small molecules with cytotoxic activities,. and consequently, causing cell death. Some central nervous system (CNS) drugs have recently demonstrated great anti-cancer potential, both in vitro, in vivo and in clinical trials, being promising candidates for drug repurposing in oncology. The present work evaluated the anti-cancer efficacy of honeybee venom in combination with chemotherapeutic or CNS drugs in HT-29 colon and MCF-7 breast cancer cell lines. The chemical characterization of a Portuguese sample of honeybee venom was done by LC-DAD-ESI/MSn analysis. For single treatments, cells were incubated with increasing concentrations of bee venom. For combination treatments, increasing concentrations of bee venom were first combined with the half-maximal inhibitory concentration (IC50) of 5-FU and DOX, in HT-29 and MCF-7 cells, respectively. Cells were also treated with increasing concentrations of bee venom in combination with the IC50 value of four CNS drugs (fluphenazine, fluoxetine, sertraline and thioridazine). Cytotoxicity was evaluated by MTT and SRB assays. The combination index (CI) value was calculated using CompuSyn software, based on the Chou–Talalay method. Synergy scores of different reference models (HSA, Loewe, ZIP and Bliss) were also calculated using SynergyFinder. The results demonstrate that honeybee venom is active against HT-29 colon and MCF-7 breast cancer cells, having better anti-tumour activity in MCF-7 cells. It was found that bee venom combined with 5-FU and fluphenazine in HT-29 cells resulted in less cytotoxic effects compared to the co-treatment of fluoxetine, sertraline and thioridazine plus bee venom, which resulted in less than 15% of viable cells for the whole range of concentrations. The combination of MCF-7 cells with repurposed drugs plus honeybee venom resulted in better anti-cancer efficacies than with DOX, notably for lower concentrations. A combination of fluoxetine and thioridazine plus honeybee venom resulted in less than 40% of viable cells for all ranges of concentrations. These results support that the combination of honeybee venom with repurposed drugs and chemotherapeutic agents can help improve their anti-cancer activity, especially for lower concentrations, in both cell lines. Overall, the present study corroborates the enormous bioactive potential of honeybee venom for colon and breast cancer treatments, both alone and in combination with chemotherapy or repurposed drugs.
- Improvement of the in vitro cytotoxic effect on HT-29 colon cancer cells by combining 5-fluorouacil and fluphenazine with green, red or brown propolisPublication . Falcão, Soraia; Duarte, Diana; Diallo, Moustapha; Santos, Joana B.; Ribeiro, Eduarda; Vale, Nuno; Vilas-Boas, MiguelCancer is regard as one of the key factors of mortality and morbidity in the world. Treatment is mainly based on chemotherapeutic drugs that, when used in targeted therapies, have serious side effects. 5-fluorouracil (5-FU) is a drug commonly used against colorectal cancer (CRC), despite its side effects. Combination of this compound with natural products is a promising source in cancer treatment research. In recent years, propolis has become the subject of intense pharmacological and chemical studies linked to its diverse biological properties. With a complex composition rich in phenolic compounds, propolis is described as showing positive or synergistic interactions with several chemotherapeutic drugs. The present work evaluated the in vitro cytotoxic activity of the most representative propolis types, such as green, red and brown propolis, in combination with chemotherapeutic or CNS drugs on HT-29 colon cancer cell lines. The phenolic composition of the propolis samples was evaluated by LC-DAD-ESI/MSn analysis. According to the type of propolis, the composition varied; green propolis was rich in terpenic phenolic acids and red propolis in polyprenylated benzophenones and isoflavonoids, while brown propolis was composed mainly of flavonoids and phenylpropanoids. Generally, for all propolis types, the results demonstrated that combing propolis with 5-FU and fluphenazine successfully enhances the in vitro cytotoxic activity. For green propolis, the combination demonstrated an enhancement of the in vitro cytotoxic effect compared to green propolis alone, at all concentrations, while for brown propolis, the combination in the concentration of 100 mu g/mL gave a lower number of viable cells, even when compared with 5-FU or fluphenazine alone. The same was observed for the red propolis combination, but with a higher reduction in cell viability. The combination index, calculated based on the Chou-Talalay method, suggested that the combination of 5-FU and propolis extracts had a synergic growth inhibitory effect in HT-29 cells, while with fluphenazine, only green and red propolis, at a concentration of 100 mu g/mL, presented synergism.
- In vitro evaluation of portuguese propolis and floral sources for antiprotozoal, antibacterial and antifungal activityPublication . Falcão, Soraia; Vale, Nuno; Cos, Paul; Gomes, Paula; Freire, Cristina; Maes, Louis; Vilas-Boas, MiguelPropolis is a beehive product with a very complex chemical composition, used since ancient times in several therapeutic treatments. As a contribution to the improvement of drugs against several tropical diseases caused by protozoa, we screened Portuguese propolis and its potential floral sources Populus x Canadensis and Cistus ladanifer against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and Trypanosoma cruzi. The toxicity against MRC-5 fibroblast cells was evaluated to assess selectivity. The in vitro assays were performed following the recommendations of WHO Special Programme for Research and Training in Tropical Diseases (TDR) and revealed moderate activity, with the propolis extracts presenting the relatively highest inhibitory effect against T. brucei. Additionally, the antimicrobial activity against Staphylococcus aureus, Candida albicans, Trichophyton rubrum and Aspergillus fumigatus was also verified with the better results observed against T. rubrum. The quality of the extracts was controlled by evaluating the phenolic content and antioxidant activity. The observed biological activity variations are associated with the variable chemical composition of the propolis and the potential floral sources under study.
- Natural sporopollenin microcarriers: Morphological insights into their functional performance for drug encapsulation and releasePublication . Aylanc, Volkan; Peixoto, Andreia F.; Akyuz, Lalehan; Vale, Nuno; Freire, Cristina; Vilas-Boas, MiguelNatural sporopollenin microcapsules (SMCs) derived from pollen offer versatility and efficiency for different applications, from environmental remediation to food and therapeutics delivery. A critical gap remains in understanding the relationship between SMCs morphologies and their effectiveness in drug loading and delivery. Herein, we encapsulated 5-Fluorouracil (5-FU), a model anticancer drug, into SMCs derived from seven bee monofloral pollens, each exhibiting distinct morphological features, and examined how their loading and release performance correlated with their morphology. Microscopic and particle size analyses revealed that the chemically purified SMCs were hollow, with sizes ranging from 11.0 to 35.6 μm, without significant size changes after drug loading. Encapsulation efficiency achieved through vacuum-assisted loading (18–28 %) generally surpassed that of passive and compression loading techniques. Moreover, there was a trend of increasing encapsulation efficiency with larger SMC sizes, albeit with some exceptions. In a sequential release environment simulating the in vitro gastrointestinal tract and colonic fermentation, smaller SMCs exhibited a faster release profile, whereas larger ones demonstrated a slower sustained release. The quantity and shape of apertures on SMCs walls significantly impacted their drug-loading capacity and release characteristics. Additionally, natural SMCs remained structurally intact even in the presence of digestive enzymes, varying pH levels, and colonic bacteria, indicating minimal degradation under these conditions. Overall, the findings highlight the significant influence of SMCs morphologies on their functional performance and provide a list of SMCs-based microstructures to guide drug release applications.
- Phenolic composition and antioxidant activity assessment of southeastern and south Brazilian propolisPublication . Coelho, Joana C.M.M.; Falcão, Soraia; Vale, Nuno; Almeida-Muradian, Ligia Bicudo; Vilas-Boas, MiguelPropolis is a resinous substance collected by honey bees Apis mellifera from several plant sources and used in the hive to seal the walls, to strengthen the ends of the honey comb or embalm dead invaders. The chemical specificity of propolis is directly determined by the variability of the plant origins and by geographical and climatic features of the collection site. The aim of this work was the quality assessment of 16 south and southeast Brazilian propolis samples through the identification and quantification of phenolic compounds using chromatographic and spectroscopic techniques such as HPLC and LC/DAD/ESI-MS n . Generally, the samples presented a phenolic profile related to Brazilian green propolis with origin in Baccharis spp. leaves, where the caffeoylquinic ac id derivatives as well as dihydrokaempferide and artepillin C were the main compounds. Moreover, DPPH • free radical-scavenging activity, reducing power and differential pulse voltammetry were applied to evaluate the antioxidant activity. Differential pulse voltammetry proved to be a rapid and easy tool for the quantification of the total electroactive species present in the samples. The results revealed a richer phenolic composition and higher bioactivity in Minas Gerais samples rather than the southern ones.
- Phenolic profiling of portuguese propolis by LC–MS spectrometry: uncommon propolis rich in flavonoid glycosidesPublication . Falcão, Soraia; Vale, Nuno; Gomes, Paula; Domingues, Maria R.M.; Freire, Cristina; Cardoso, Susana M.; Vilas-Boas, MiguelPropolis is a chemically complex resinous substance collected by honeybees (Apis mellifera) from tree buds, comprising plant exudates, secreted substances from bee metabolism, pollen and waxes. Its chemical composition depends strongly on the plant sources available around the beehive, which have a direct impact in the quality and bioactivity of the propolis. Being as Portugal is a country of botanical diversity, the phenolic characterisation of propolis from the different regions is a priority. Objective Extensive characterisation of the phenolic composition of Portuguese propolis from different continental regions and islands. Method Forty propolis ethanolic extracts were analysed extensively by liquid chromatography with diode-array detection coupled to electrospray ionisation tandem mass spectrometry (LC-DAD-ESI-MSn). Results Seventy-six polyphenols were detected in the samples and two groups of propolis were established: the common temperate propolis, which contained the typical poplar phenolic compounds such as flavonoids and their methylated/esterified forms, phenylpropanoid acids and their esters, and an uncommon propolis type with an unusual composition in quercetin and kaempferol glycosides - some of them never described in propolis. Conclusion The method allowed the establishment of the phenolic profile of Portuguese propolis from different geographical locations, and the possibility to use some phenolic compounds, such as kaempferol-dimethylether, as geographical markers. Data suggest that other botanical species in addition to poplar trees can be important sources of resins for Portuguese propolis. Copyright (c) 2012 John Wiley & Sons, Ltd.
- Phenolic quantification and botanical origin of Portuguese propolisPublication . Falcão, Soraia; Tomás, Andreia; Vale, Nuno; Gomes, Paula; Freire, Cristina; Vilas-Boas, MiguelThe production of propolis by honeybees results from a selective collection of exudates from leaf buds and plants present in the hive neighborhood leading to a resin with many potentialities in the pharmaceutical industry. This study aims to quantify the phenolic content in propolis from different Portuguese regions and in the potential floral sources, Populus x Canadensis Moench buds and Cistus ladanifer L., in order to establish links with geographical and botanical origin. The Portuguese propolis revealed a phenolic profile with marked differences in concentrations: the richness in flavonoids is common in all regions, but more evident in propolis from central interior, south and Madeira. The composition of poplar type propolis common in temperate zones was observed in the north, central coast and Azores, while the central interior and south samples, with a composition rich in kaempferol derivatives, resemble the C. ladanifer exudates, a spontaneous bush widespread in the Mediterranean. The compound kaempferol-3,7-dimethyl-ether, absent in the poplar type propolis, can be regard as a possible marker for the discrimination of these two types of propolis. (C) 2013 Elsevier B.V. All rights reserved.
- Screening of portuguese propolis and its plant sources for inhibitory activity against pathogenic protozoaPublication . Vale, Nuno; Falcão, Soraia; Batista, Vânia; Freire, Cristina; Maes, Louis; Vilas-Boas, MiguelPropolis is a beehive product with a very complex chemical composition, widely used in folk medicine because of its several therapeutic activities. Its biological properties and chemical composition may vary according to the geografic location and to the different plant sources. Recently, we reported the mechanism for extration and propolis sample preparation (Falca˜o et al, Anal. Bioanal. Chem., 2010, 396: 887-897). After that, we developed a new study for Portuguese propolis and plant samples found around the hive, and we present in this study the activity of these samples against pathogenic protozoa. Two different raw propolis samples from the northeast and centre of Portugal, both acquired from local beekeepers, were analysed in the present work. For the plant samples we collect the buds exudates and surface material present on the leaves, stems of Populus nigra male and female specimens and Cistus lanadifer. These samples were screened for in vitro activity against the pathogenic protozoa Plasmodium falciparum, Leishmania infantum, Trypanosoma cruzi and Trypanosoma bruci. To assess selectivity of action, cytodoxicity against MRC-5 fibroblast cells was also evaluated. We present in this communication interesting results, according to criteria set up by the WHO Special Programme for Research & Training in Tropical Diseases.
- Sporopollenin-based bio-microcapsules as green carriers for controlled delivery of pharmaceutical drugsPublication . Aylanc, Volkan; Peixoto, Andreia F.; Vale, Nuno; Freire, Cristina; Vilas-Boas, MiguelThe production and design of innovative in-body microcarrier platforms for the controlled delivery of bioactive substances to predefined sites continue to hold substantial promise for biotechnology and medicine by increasing their therapeutic benefits. In this scope, plant pollen-based biocapsules, sporopollenin structures, have emerged as an alternative to synthetic ones due to their low-cost, highly uniform size distribution, resistance to physical and chemical conditions, and renewable green sources. Sporopollenin-based microcarriers, acting as a cargo and protective system, can be engineered to tune the biodistribution and therapeutic efficacy of encapsulated pharmaceuticals. Despite these benefits, the attained biocapsules directly from the plant, which have been the subject of research for nearly two decades, face several challenges and limitations, such as their availability without disrupting their layer integrity for all pollen species, dosage tuning, and the exact control of their responses on the immune system. Recent reports of successful oral administration seem, nevertheless, to bring them one step closer to clinical applications. Herein, we discuss the challenges, possible solutions for broadening natural resources and access to pollen, their further development towards the improvement of controlled release and prolonging the residence time in the intestinal lumen, and promising applications in the in vivo models and clinical trials, focusing on progress in biocapsule technology and the main events occurring along the way.