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- Comprehensive review on the interaction between natural compounds and brain receptors: Benefits and toxicityPublication . Silva, Ana R.; Grosso, Clara; Delerue-Matos, Cristina; Rocha, João M.Given their therapeutic activity, natural products have been used in traditional medicines throughout the centuries. The growing interest of the scientific community in phytopharmaceuticals, and more recently in marine products, has resulted in a significant number of research efforts towards understanding their effect in the treatment of neurodegenerative diseases, such as Alzheimer's (AD), Parkinson (PD) and Huntington (HD). Several studies have shown that many of the primary and secondary metabolites of plants, marine organisms and others, have high affinities for various brain receptors and may play a crucial role in the treatment of diseases affecting the central nervous system (CNS) in mammalians. Actually, such compounds may act on the brain receptors either by agonism, antagonism, allosteric modulation or other type of activity aimed at enhancing a certain effect. The current manuscript comprehensively reviews the state of the art on the interactions between natural compounds and brain receptors. This information is of foremost importance when it is intended to investigate and develop cutting-edge drugs, more effective and with alternative mechanisms of action to the conventional drugs presently used for the treatment of neurodegenerative diseases. Thus, we reviewed the effect of 173 natural products on neurotransmitter receptors, diabetes related receptors, neurotrophic factor related receptors, immune system related receptors, oxidative stress related receptors, transcription factors regulating gene expression related receptors and blood-brain barrier receptors.
- Evaluation of the Biological Potential of Himanthalia elongata (L.) S.F.Gray and Eisenia bicyclis (Kjellman) Setchell Subcritical Water ExtractsPublication . Gomes, Inês; Rodrigues, Helena; Rodrigues, Carla; Oliveira, Marta Marques; Paíga, Paula; Paiva, Alexandre; Simões, Pedro; Fernandes, Virgínia Cruz; Vieira, Mónica; Delerue-Matos, Cristina; Soares, Cristina; Grosso, ClaraNeuroprotection is a need that remains unmet in treating chronic neurodegenerative disorders, despite decades of extensive research. To find new neuroprotective compounds, extracts of Himanthalia elongata (L.) S.F.Gray and of Eisenia bicyclis (Kjellman) Setchell were obtained through subcritical water extraction applying a four-step temperature gradient. The fractions obtained were screened against brain enzymes involved in neurodegenerative etiology, namely in Alzheimer’s and Parkinson’s diseases, and against reactive oxygen and nitrogen species, all contributing factors to the progression of neurodegeneration. Results showed no significant enzyme inhibition but strong radical scavenging activities, particularly in the fourth fraction, extracted at the highest temperature (250 °C), highlighting their ability to retard oxidative and nitrosative stresses. At higher temperatures, fractions were composed of phenolic compounds and Maillard reaction products, a combination that contributed to their antioxidant activity and, consequently, their neuroprotective properties. All fractions were evaluated for the presence of iodine, 14 organochlorine and 7 organophosphorus pesticides, and pharmaceuticals used in Alzheimer’s and Parkinson’s diseases (14), psychiatric drugs (8), and metabolites (8). The fractions studied did not present any of the screened contaminants, and only fraction 1 of E. bicyclis should be used with caution due to iodine content.
- Recent advances in biological properties of brown algae-derived compounds for nutraceutical applicationsPublication . Silva, Aurora; Cassani, Lucia; Grosso, Clara; Garcia-Oliveira, Paula; Morais, Stephanie; Echave, Javier; Carpena, Maria; Xiao, Jianbo; Barroso, M. Fátima; Simal-Gandara, Jesus; Prieto, Miguel A.The increasing demand for nutraceuticals in the circular economy era has driven the research toward studying bioactive compounds from renewable underexploited resources. In this regard, the exploration of brown algae has shown significant growth and maintains a great promise for the future. One possible explanation could be that brown algae are rich sources of nutritional compounds (polyunsaturated fatty acids, fiber, proteins, minerals, and vitamins) and unique metabolic compounds (phlorotannins, fucoxanthin, fucoidan) with promising biological activities that make them good candidates for nutraceutical applications with increased value-added. In this review, a deep description of bioactive compounds from brown algae is presented. In addition, recent advances in biological activities ascribed to these compounds through in vitro and in vivo assays are pointed out. Delivery strategies to overcome some drawbacks related to the direct application of algae-derived compounds (low solubility, thermal instability, bioavailability, unpleasant organoleptic properties) are also reviewed. Finally, current commercial and legal statuses of ingredients from brown algae are presented, considering future therapeutical and market perspectives as nutraceuticals.
- Multi-target neuroprotective effects of herbal medicines for Alzheimer's diseasePublication . Fernandes, Filipe; Barroso, M. Fátima; De Simone, Angela; Emriková, Eliška; Dias-Teixeira, Mónica; Pereira, José Paulo; Chlebek, Jakub; Fernandes, Virgínia Cruz; Rodrigues, Francisca; Andrisano, Vincenza; Delerue-Matos, Cristina; Grosso, ClaraEthnopharmacological relevance Alzheimer's disease is the most common form of dementia, but its treatment options remain few and ineffective. To find new therapeutic strategies, natural products have gained interest due to their neuroprotective potential, being able to target different pathological hallmarks associated with this disorder. Several plant species are traditionally used due to their empirical neuroprotective effects and it is worth to explore their mechanism of action. Aim of the study This study intended to explore the neuroprotective potential of seven traditional medicinal plants, namely Scutellaria baicalensis, Ginkgo biloba, Hypericum perforatum, Curcuma longa, Lavandula angustifolia, Trigonella foenum-graecum and Rosmarinus officinalis. The safety assessment with reference to pesticides residues was also aimed. Materials and methods Decoctions prepared from these species were chemically characterized by HPLC-DAD and screened for their ability to scavenge four different free radicals (DPPH•, ABTS•+, O2•‒ and •NO) and to inhibit enzymes related to neurodegeneration (cholinesterases and glycogen synthase kinase-3β). Cell viability through MTT assay was also evaluated in two different brain cell lines, namely non-tumorigenic D3 human brain endothelial cells (hCMEC/D3) and NSC-34 motor neurons. Furthermore, and using GC, 21 pesticides residues were screened. Results Regarding chemical composition, chromatographic analysis revealed the presence of several flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, one alkaloid and one naphthodianthrone in the seven decoctions. All extracts were able to scavenge free radicals and were moderate glycogen synthase kinase-3β inhibitors; however, they displayed weak to moderate acetylcholinesterase and butyrylcholinesterase inhibition. G. biloba and L. angustifolia decoctions were the less cytotoxic to hCMEC/D3 and NSC-34 cell lines. No pesticides residues were detected. Conclusions The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.
- New insights of phytochemical profile and in vitro antioxidant and neuroprotective activities from optimized extract of Horned Melon fruitPublication . Vieira, Elsa F.; Podlasiak, Martyna; Moreira, Manuela M.; Grosso, Clara; Rodrigues, Francisca; Fernandes, Virgínia Cruz; Delerue-Matos, CristinaThis study aimed the optimization of antioxidant activity, total phenolic compounds (TPC) and total carotenoids of Horned Melon fruit submitted to maceration extraction, using ethanol as solvent. Optimization was performed by Box–Behnken design on three levels and three variables: extraction temperature (25 °C, 55 °C, and 85 °C), extraction time (0.5, 2.0, and 3.5 h) and ethanol concentration (10%, 50%, and 90%). The optimal conditions to improve the carotenoids extraction was 55 °C, 1.5 h and 86% ethanol, whereas the antiradical/antioxidant activity (ABTS and FRAP assays) and TPC were enhanced at 45 °C for 2.0 h and 40% ethanol. The optimal antioxidant extract was characterized regarding the phenolic composition and in vitro neuroprotective activities. The phenolic composition revealed the presence of high amounts of gallic acid (11.7 ± 0.6 mg/100 g dw) and protocatechuic acid (7.69 ± 0.38 mg/100 g dw). However, this extract presented a weak activity against Monoamine oxidase A (11.8 ± 2.3% inhibition at 2.7 mg/mL) and did not display anti-cholinesterase activity at the maximum concentration tested (1.3 mg/mL). Maceration was an efficient extraction technique to recover polyphenols and carotenoids from Horned Melon fruit. The optimized model can be very useful for food and pharmaceutical industries
- A Critical Comparison of the Advanced Extraction Techniques Applied to Obtain Health-Promoting Compounds from SeaweedsPublication . Quitério, Eva; Grosso, Clara; Ferraz, Ricardo; Delerue-Matos, Cristina; Soares, CristinaMarine macroalgae are rich in bioactive compounds that can be applied in several fields, mainly food, cosmetics, and medicine. The health-promoting effects of bioactive compounds, such as polyphenols, polysaccharides, carotenoids, proteins, and fatty acids, have been increasingly explored, especially regarding their antioxidant activity and improvement in human health. To extract these valuable compounds, advanced technologies that include Supercritical-Fluid Extraction (SFE), Pressurised-Liquid Extraction (PLE), Ultrasound-Assisted Extraction (UAE), Microwave-Assisted Extraction (MAE), Enzyme-Assisted Extraction (EAE), Ultrasound-Microwave-Assisted Extraction (UMAE) and Liquefied Gas Extraction (LGE) have been assessed due to their notable advantages over the conventional methods (Solid–Liquid and Soxhlet extraction). These advanced techniques are considerably influenced by different extraction parameters such as temperature, pressure, type of solvent, extraction time, solvent:solid material ratio, power (MAE, UAE, and UMAE), enzymes used (EAE), and factors related to the macroalgae matrix itself. Optimizing these process parameters for each method is critical to obtain better efficiency results for the targeted bioactive compounds. Macroalgae are natural sources with undeniable beneficial effects on human health. In this context, optimising the extraction techniques discussed in this review should prioritise exploiting these valuable resources’ wide range of bioactive properties
- Biological Potential, Gastrointestinal Digestion, Absorption, and Bioavailability of Algae-Derived Compounds with Neuroprotective Activity: A Comprehensive ReviewPublication . Martins, Bruna; Vieira, Mónica; Delerue-Matos, Cristina; Grosso, Clara; Soares, CristinaCurrently, there is no known cure for neurodegenerative disease. However, the available therapies aim to manage some of the symptoms of the disease. Human neurodegenerative diseases are a heterogeneous group of illnesses characterized by progressive loss of neuronal cells and nervous system dysfunction related to several mechanisms such as protein aggregation, neuroinflammation, oxidative stress, and neurotransmission dysfunction. Neuroprotective compounds are essential in the prevention and management of neurodegenerative diseases. This review will focus on the neurodegeneration mechanisms and the compounds (proteins, polyunsaturated fatty acids (PUFAs), polysaccharides, carotenoids, phycobiliproteins, phenolic compounds, among others) present in seaweeds that have shown in vivo and in vitro neuroprotective activity. Additionally, it will cover the recent findings on the neuroprotective effects of bioactive compounds from macroalgae, with a focus on their biological potential and possible mechanism of action, including microbiota modulation. Furthermore, gastrointestinal digestion, absorption, and bioavailability will be discussed. Moreover, the clinical trials using seaweed-based drugs or extracts to treat neurodegenerative disorders will be presented, showing the real potential and limitations that a specific metabolite or extract may have as a new therapeutic agent considering the recent approval of a seaweed-based drug to treat Alzheimer’s disease
- Phytochemical Characterization and Biological Evaluation of the Aqueous and Supercritical Fluid Extracts from Salvia sclareoides BrotPublication . Batista, Daniela; Falé, Pedro L.; Serralheiro, Maria L.; Araújo, Maria-Eduarda; Dias, Catarina; Branco, Isabel; Grosso, Clara; Coelho, José; Palavra, António; Madeira, Paulo J. A.; Martins, Alice; Rauter, Amélia P.Plants belonging to the genus Salvia (Lamiaceae) are known to have a wide range of biological properties. In this work, extracts obtained from the aerial parts of Salvia sclareoides Brot. were evaluated to investigate their chemical composition, toxicity, bioactivity, and stability under in vitro gastrointestinal conditions. The composition of the supercritical fluid extract was determined by GC and GC-MS, while the identification of the infusion constituents was performed by HPLC-DAD and LC-MS. The in vitro cytotoxicity of both extracts (0-2 mg/mL) was evaluated in Caco-2 cell lines by the MTT assay. The anti-inflammatory and anticholinesterase activities were determined through the inhibition of cyclooxygenase-1 and acetylcholinesterase enzymes, while β-carotene/linoleic acid bleaching test and the DPPH assays were used to evaluate the antioxidant activity. The infusion inhibited cyclooxygenase-1 (IC50 = 271.0 μg/mL), and acetylcholinesterase (IC50 = 487.7 μg/ mL) enzymes, also demonstrated significant antioxidant properties, as evaluated by the DPPH (IC50 = 10.4 μg/mL) and β-carotene/linoleic acid (IC50 = 30.0 μg/mL) assays. No remarkable alterations in the composition or in the bioactivities of the infusion were observed after in vitro digestion, which supports the potential of S. sclareoides as a source of bioactive ingredients with neuroprotective, anti-inflammatory and antioxidant properties.