Pharmacology (medical), Agricultural and Biological Sciences, Biochemistry, Genetics and Molecular Biology
9
Scopus Publications
Scopus Publications
Orodispersible films containing chestnut shell phenolics for buccal delivery: a preclinical approach for oral mucositis prevention Ana Sofia Ferreira, Ana Margarida Silva, Catarina Macedo, Emily P. Laveriano-Santos, Julián Lozano-Castellón, Rosa M. Lamuela-Raventós, Jaroslava Švarc-Gajíc, Paulo C. Costa, Cristina Delerue-Matos, Francisca Rodrigues Frontiers in Medical Technology, 2025 IntroductionOral mucositis (OM) is a prevalent complication of cancer treatment that causes painful erythematous and ulcerated lesions in oral mucosa. Current treatments lack efficacy, being natural compounds explored as alternatives. Chestnut shells (CS) are rich in (poly)phenols with antioxidant, anti-inflammatory, and antitumor properties. This study aims to develop orodispersible films (OFs) with CS extract as active ingredient to manage OM.MethodsOFs, prepared by solvent casting and incorporating the CS extract, were characterized regarding physicochemical, antioxidant/antiradical, and anticancer properties, as well as bioactive compounds permeation through in vitro and ex vivo buccal models.ResultsOFs revealed excellent features: thickness (125 µm), tensile strength (43.05 MPa), elongation (75.28%), weight (19 mg/cm2), moisture content (4.25%), and disintegration time (20.43 min). Significant antioxidant/antiradical activities were observed (TPC = 37.05 mg GAE/g film; DPPH = 143.42 mg TE/g film; FRAP = 0.142 µmol FSE/g film). LC-ESI-LTQ-Orbitrap-HRMS analysis confirmed the high permeation of sebacic acid, epicatechin, isorhamnetin, protocatechuic acid, and L-tyrosine across both models, while cytotoxicity assays in oral epithelial cell lines (HSC3 and TR146) demonstrated the cytocompatibility.ConclusionCS-OFs offers a promising approach for preventing and treating OM, enhancing efficacy and patient comfort by delivering bioactive compounds directly to the oral mucosa.
Design of advanced buccal films with kiwiberry extract to prevent oral mucositis: From in vitro buccal models to ex vivo studies Filipa Teixeira, Ana Margarida Silva, Catarina Macedo, Berta Estevinho, Stefania Sut, Stefano Dall’Acqua, Cristina Delerue-Matos, Paulo C. Costa, Francisca Rodrigues Journal of Drug Delivery Science and Technology, 2024 Oral mucositis (OM) is a common side effect of cancer treatments characterized by disruption of the oral mucosa integrity, inflammation, and pain. The treatment strategies to prevent and treat OM are still unsatisfactory, leading to the search of new active compounds, particularly from natural sources, such as Actinidia arguta fruits. A. arguta is a perennial vine and its fruit, commonly known as kiwiberry, has been associated with different therapeutic properties and pro-healthy benefits, particularly antioxidant, anti-inflammatory and anticancer effects. These bioactive properties are due to the fruit outstanding content in phenolic compounds, vitamins, and organic acids, which attracted the researcher's attention for potential application in pharmaceutical industry. The aim of this study is to develop buccal films with A. arguta fruit extract as active ingredient to prevent OM symptoms. The films were prepared by solvent casting after placing 50 g of a buccal film mixture prepared with 1% of HPMC K100 LV EP, 2.5% glycerin, and 100 mL of A. arguta extract as solvent. Different films parameters were assessed, namely physical features (weight: 194.8 mg; thickness: 0.37 mm; disintegration time: 15.05 min; moisture content: 10.53%; swelling capacity: 55.95%), mechanical properties (resistance to extension: 10.11 N; percent of elongation: 36.10%; Young's modulus: 0.0034 MPa) and antioxidant/antiradical activities (TPC = 6.46 mg GAE/g film; FRAP = 49.45 μmol FSE/g film; ABTS = 3.74 mg AAE/g film; DPPH = 4.90 mg TE/g film). In vitro cell assays attested the absence of negative effects on HSC-3 and TR146 oral cell lines. Most important, the compounds release profile were assessed through in vitro and ex vivo models coupled to LC/DAD-ESI-MS quantification and the results revealed high permeation of rutin, quercetin-3- O -glucoside and catechin. Overall, these results highlight the significant potential of buccal films with A. arguta fruit extract to prevent OM condition. • A. arguta fruits are extraordinary candidates for oral mucositis prevention. • Buccal films with A. agruta fruit extract were successfully produced. • Buccal films revealed great physical, mechanical, and structural features. • The buccal films proved to be safe for oral application. • The majority of the films' components permeated both cell and tissue layers.
Bioactive compounds from Actinidia arguta fruit as a new strategy to fight glioblastoma Catarina Macedo, Paulo C. Costa, Francisca Rodrigues Food Research International, 2024 In recent years, there has been a significant demand for natural products as a mean of disease prevention or as an alternative to conventional medications. The driving force for this change is the growing recognition of the abundant presence of valuable bioactive compounds in natural products. On recent years Actinia arguta fruit, also known as kiwiberry, has attracted a lot of attention from scientific community due to its richness in bioactive compounds, including phenolic compounds, organic acids, vitamins, carotenoids and fiber. These bioactive compounds contribute to the fruit's diverse outstanding biological activities such as antioxidant, anti-inflammatory, neuroprotective, immunomodulatory, and anti-cancer properties. Due to these properties, the fruit may have the potential to be used in the treatment/prevention of various types of cancer, including glioblastoma. Glioblastoma is the most aggressive form of brain cancer, displaying 90 % of recurrence rate within a span of 2 years. Despite the employment of an aggressive approach, the prognosis remains unfavorable, emphasizing the urgent requirement for the development of new effective treatments. The preclinical evidence suggests that kiwiberry has potential impact on glioblastoma by reducing the cancer self-renewal, modulating the signaling pathways involved in the regulation of the cell phenotype and metabolism, and influencing the consolidation of the tumor microenvironment. Even though, challenges such as the imprecise composition and concentration of bioactive compounds, and its low bioavailability after oral administration may be drawbacks to the development of kiwiberry-based treatments, being urgent to ensure the safety and efficacy of kiwiberry for the prevention and treatment of glioblastoma. This review aims to highlight the potential impact of A. arguta bioactive compounds on glioblastoma, providing novel insights into their applicability as complementary or alternative therapies.
Valorization of Actinidia spp. by-products and wastes for nutraceutical applications Ana Margarida Silva, Catarina Macedo, Piotr Latocha, Paulo Costa, Cristina Delerue‐Matos, Francisca Rodrigues Nutraceutics from Agri Food by Products, 2023 Circular economy is an essential point of sustainable development that supports waste minimization and efficient use of resources. The reuse and recovery of by-products and wastes from different fruit species is a world challenge. Actinidia spp. is an example of a fruit genus widely disseminated worldwide and coupled with an enormous economic value. This genus is composed by 54 species, of which 2 are of great commercial interest ( A. chinensis var. chinensis, A. chinensis var. deliciosa , and A. arguta ). The growing interest in the cultivation of kiwi leads to the generation of different by-products and wastes (e.g., leaves, stems, damage fruits). In addition, the widespread interest observed has created a demand for the identification of the bioactive compounds present in its by-products and wastes. Different compounds have been identified, such as polyphenols, vitamins, fiber, and phenolic compounds, which have been associated with several beneficial health effects (e.g., antioxidant, anti-inflammatory, antimicrobial, neuroprotective, and anti-obesity effects). Therefore, kiwi by-products and wastes could be valorized as new sources of nutraceuticals ingredients. This chapter aims to explore the pro-healthy properties of Actinidia genus by-products and wastes, reviewing the most recent studies and overview the challenges for its validation as new nutraceutical ingredients.
Insights into the polyphenols extraction from Actinidia arguta fruit (kiwiberry): A source of pro-healthy compounds Catarina Macedo, Ana Margarida Silva, Ana Sofia Ferreira, María de la Luz Cádiz-Gurrea, Álvaro Fernández-Ochoa, Antonio Segura-Carretero, Cristina Delerue-Matos, Paulo Costa, Francisca Rodrigues Scientia Horticulturae, 2023 Actinidia arguta fruit (also known as kiwiberry) has a remarkable phytochemical profile, being reported as a promising preventive agent/treatment for chronic diseases and a desirable source of bioactive molecules for pharmaceutical and cosmetic industries. Despite these promising indications, investigating the full potential of A. arguta fruit remains an unmet need for health applications. This work aims to determine the optimal extraction conditions of antioxidant/antiradical compounds from A. arguta fruit (commonly known as kiwiberry), using the Response Surface Methodology (RSM). The effects of probe amplitude (30%-70%), sonication time (5-30 min) and water:ethanol solvent ratio (0%-100%) were assessed. The optimal extraction conditions were achieved using 50% of water, during 17.5 min and using an amplitude of 50%. A total of 22 compounds, including 6 flavonoids and 4 phenolic acids, were identified in the optimal extract through HPLC-ESI-QTOF-MS, which exhibited outstanding antioxidant and antiradical activities (TPC = 18.705 mg GAE/g dw; FRAP = 186.876 µmol FSE/g dw; ABTS = 16.334 mg AAE/g dw; O2·− IC50 = 829.384 µg/mL; HOCl IC50 = 16.895 µg/mL; ROO· = 0.18 µg TE/mg dw). Moreover, it displayed antimicrobial activity against Staphylococcus aureus (MIC = 32 mg/mL) and Pseudomonas gingivalis (MIC = 64 mg/mL) and reduced the growth rate of Escherichia coli. In-vitro assays demonstrated that the optimal extract successfully decreased the viability of two human carcinoma cell lines, namely TR146 and HSC-3, at 500 µg/mL and above 500 µg/mL, respectively. The present study showed that A. arguta fruit is a rich source of compounds with potential to be used for pro-healthy purposes.
Natural Products for the Prevention and Treatment of Oral Mucositis—A Review Ana Sofia Ferreira, Catarina Macedo, Ana Margarida Silva, Cristina Delerue-Matos, Paulo Costa, Francisca Rodrigues International Journal of Molecular Sciences, 2022 Cancer, a major world public health problem, is associated with chemotherapy treatments whose administration leads to secondary concerns, such as oral mucositis (OM). The OM disorder is characterized by the presence of ulcers in the oral mucosa that cause pain, bleeding, and difficulty in ingesting fluids and solids, or speaking. Bioactive compounds from natural sources have arisen as an effective approach for OM. This review aims to summarize the new potential application of different natural products in the prevention and treatment of OM in comparison to conventional ones, also providing a deep insight into the most recent clinical studies. Natural products, such as Aloe vera, Glycyrrhiza glabra, Camellia sinensis, Calendula officinalis, or honeybee crops, constitute examples of sources of bioactive compounds with pharmacological interest due to their well-reported activities (e.g., antimicrobial, antiviral, anti-inflammatory, analgesic, or wound healing). These activities are associated with the bioactive compounds present in their matrix (such as flavonoids), which are associated with in vivo biological activities and minimal or absent toxicity. Finally, encapsulation has arisen as a future opportunity to preserve the chemical stability and the drug bioa vailability of bioactive compounds and, most importantly, to improve the buccal retention period and the therapeutic effects.
Microwave‐ and Ultrasound‐Assisted Extraction of Cucurbita pepo Seeds: a Comparison Study of Antioxidant Activity, Phenolic Profile, and In‐Vitro Cells Effects Catarina Macedo, Ana Margarida Silva, Ana Sofia Ferreira, Manuela M. Moreira, Cristina Delerue-Matos, Francisca Rodrigues Applied Sciences Switzerland, 2022 Nowadays there is a growing demand for nutraceuticals to prevent diseases related to redox imbalances, such as atherosclerosis and diabetes, being crucial to search for new matrixes rich in bioactive compounds. This work aims to characterize the value-added compounds extracted from Curcubita pepo seeds using green methodologies, namely microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE), employing water as an extracting solvent for two ratios (condition 1: 1 mg/20 mL; condition 2: 2.5 mg/20 mL). The extract with the best antioxidant/antiradical activity in FRAP (71.09 μmol FSE/g DW) and DPPH (5.08 mg TE/g DW) assays was MAE condition 1, while MAE condition 2 exhibited the highest activity in the ABTS assay (13.29 mg AAE/g DW) and TPC (16.89 mg GAE/g DW). A remarkable scavenging capacity was observed, particularly for HOCl, with IC50 values ranging from 1.88–13.50 μg/mL. A total of 21 phenolic compounds were identified, being catechin (4.567–7.354 mg/g DW), caffeine (1.147–2.401 mg/g DW) and gallic acid (0.945–1.337 mg/g DW) predominant. No adverse effects were observed on Caco-2 viability after exposure to MAE extracts, while the other conditions led to a slight viability decrease in NSC-34. These results highlighted that the extract from MAE condition 2 is the most promising as a potential nutraceutical ingredient.
Development and optimization of a topical formulation with castanea sativa shells extract based on the concept “quality by design” Nágilla Oliveira, Maria de la Luz Cádiz-Gurrea, Ana Margarida Silva, Catarina Macedo, Francisca Rodrigues, Paulo Costa Sustainability Switzerland, 2022 The proposed study aims to develop and optimize a topical formulation with Castanea sativa shells extract considering the concept of Quality by Design, focusing on a planned development that consider the vulnerabilities of the entire process through risk analysis tools and design of experiments (DoE). A Box–Behnken design with three factors and three levels was used as a statistical tool for the execution of the DoE and the analysis of the response surface methodology responses. The independent variables studied were the quantity of sodium lauryl sulfate (%) (X1), beeswax (%) (X2) and macadamia oil (%) (X3); the dependent variables were pH (Y1), viscosity (Y2) and adhesiveness (Y3). According to the mathematical model, the optimal formulation contains 0.93% of sodium lauryl sulfate, 5.00% of beeswax and 10.00% of macadamia oil. The optimal formulation with the extract was prepared and characterized over the time, regarding organoleptic and technological characteristics, allowing conclusions to be reached regarding its stability. The formulation presented a pleasant odor and was light brown in color, it also demonstrated pseudoplastic-thixotropic behavior and a small reduction in the formulation consistency after 30 days of storage. This study demonstrated the efficiency of the Quality by Design methodology to understand the product variability, supporting that this approach favors a better understanding of the whole process and enables to design a robust development stage, reducing costs and generating high-quality products.
