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TBCCD1 and OFD1, a novel centrosomal protein partnership with a role in human ciliopathies?
Publication . Veiga, Joaquim; Carmona, Bruno; Camelo, Carolina; Pereira, Dulce; Marinho, H. Susana; Soares, Helena
Cilia are hair-like appendages, consisting of a microtubule (MT)-based ciliary axoneme, that fulfill critical motility and sensory functions required for normal embryonic development and also for homeostasis of adult tissues. At their base, cilia have a centriole/basal body, which can be derived from the centrosome, and that nucleates the ciliary axoneme (primary cilia). Centrosomes consist of a pair of centrioles surrounded by the pericentriolar matrix that nucleate/organize the cytoskeleton and are implicated in cell migration, adhesion and polarity, while in mitosis they assist spindle pole formation.
Phenolic compounds from Actinidia deliciosa leaves: Caco-2 permeability, enzyme inhibitory activity and cell protein profile studies
Publication . Henriques, Joana; Fale, Pedro; Pacheco, Rita; Florêncio, Maria Helena; Serralheiro, Maria Luisa
Chemical compounds from leaves of fruit-producing trees, a waste from agricultural activity can be isolated and used as a source of natural bioactive chemicals. Boiling water was used as an extractant of bioactive compounds from Actinidia deliciosa leaves and co-extracted fibres were removed with ethanol precipitation. Rutin and quercitrin were the main flavonoids identified and quantified by RP-HPLC-DAD. No cytotoxicity was detected for any of the extracts towards Caco- 2 cell line. A permeation of approx. 14% of extract components through the cells monolayer was determined. The cell protein profile of Caco-2 cells was modified when in the presence of the fibre-free extract and transketolase was the protein over-expressed in the presence of polyphenols. Acetylcholinesterase inhibitory activity was also studied, IC50 of 0.56 mg/mL was obtained with the fibre-free extract. A. deliciosa leaves are a good source of phenolic compounds and, therefore, some advantage may be taken of this agricultural residue, due to their biological activity.
Bioactivities of decoctions from Plectranthus species related to their traditional use on the treatment of digestive problems and alcohol intoxication
Publication . Brito, Elsa; Gomes, Emma; Fale, Pedro; Borges, Carlos; Pacheco, Rita; Teixeira, Vítor; Machuqueiro, Miguel; Ascensão, Lia; Serralheiro, Maria Luisa
Ethnopharmacological relevance Decoctions of Plectranthus species are traditionally ingested after large meals for treatment of food digestion and alcohol abuse. Aim of the study This study aims at associating the digestion-related ethno-uses of Plectranthus species decoctions to molecular mechanism that might explain them: easing digestion (AChE inhibition) and treating hangover (ADH inhibition) Material and methods Decoctions from Plectranthus species were analysed for their alcohol dehydrogenase (ADH) inhibition and acetylcholinesterase (AChE) inhibition, related with alcohol metabolism and intestinal motility, respectively. Identification of the active components was carried out by LC-MS/MS and the docking studies were performed with AChE and the bioactive molecules detected. Results All decoctions inhibited ADH activity. This inhibition was correlated with their rosmarinic acid (RA) content, which showed an IC50 value of 19 μg/mL, similar to the reference inhibitor CuCl2. The presence of RA also leads to most decoctions showing AChE inhibiting capacity. P. zuluensis decoction with an IC50 of 80 μg/mL presented also medioresinol, an even better inhibitor of AChE, as indicated by molecular docking studies. Furthermore, all decoctions tested showed no toxicity towards two human cell lines, and a high capacity to quench free radicals (DPPH), which also play a helpful in the digestive process, related with their RA content. Conclusions All activities presented by the RA-rich Plectranthus decoctions support their use in treating digestion disorders and P. barbatus could explain its use also for alleviating hangover symptoms. Medioresinol, which is present in P. zuluensis, exhibited a significant AChE inhibition and may provide, in the future, a new lead for bioactive compounds.
BioMol4Health_Biological chemistry: longevity in a cup of tea
Publication . RESSAISSI, Asma; Fale, Pedro; Pacheco, Rita; Serralheiro, Maria Luisa
Infusions have been studied on what concerns Alzheimer Disease, digestive process, diet cholesterol absorption and its biosynthesis inhibition. In the first two cases the inhibition of acetylcholinesterase (AChE) has been addressed. In the last two situations, an in vitro intestinal barrier has been simulated and the inhibition of the regulator enzyme (HMGR) in cholesterol biosysnthesis pathway has been studied. AChE has been the target of infusions inhibitory activity as its inhibition has been seen to improve cognition and global functioning1 in AD suffering people and to improve the gastrointestinal motility2. Given to lab animals the compounds presente in the infusions were able to reach the brain and inhibit the enzyme3. The effect of infusions on cholesterol bioavailability pointed out that some infusions were able to reduce cholesterol permeation4 and also to have some inhibitory activity5. Studies have indicated that phenolics are able to modify the cell proteome6. The infusions have also been shown to modify the amount of cholesterol transporter proteins in cell membrane and this maybe one of possible explanations for the reduction in cholesterol transport detected under the effect of infusions, on some people ando n simulated intestinal barrier.
Serum albumin modulates the bioactivity of rosmarinic acid
Publication . Brito, Elsa; Silva, André; Fale, Pedro; Pacheco, Rita; Serralheiro, António; Haris, Parvez I.; Ascensão, Lia; Serralheiro, Maria Luisa
Rosmarinic acid (RA) is a phenolic compound with biological activity. The objective of the present study was to investigate whether this compound kept its biological activity in the presence of proteins. For this purpose, bovine serum albumin (BSA) was used as a model protein, and the capacity of the RA to inhibit acetylcholinesterase (AChE) and affect antioxidant activity was evaluated in the absence and presence of BSA. A mixture of phenolic compounds containing RA, obtained from a medicinal plant was added to this study. The AChE inhibitory activity of RA was reduced by *57% in the presence of BSA, while the antioxidant activity increased. These results lead to the investigation of the effect of RA on the BSA structure using Fourier transform infrared spectroscopy (FTIR). At 37 C and higher temperatures, RA caused a decrease in the temperature modifications onthe proteinstructure. Furthermore, FTIR and native-gel analysis revealed that protein aggregation/ precipitation, induced bytemperature, wasreduced in thepresence of RA. The novelty of the present work resides in thestudy of the enzyme inhibitory activity and antioxidant capacity of polyphenols, such as RA, in the presence of a protein. The findings highlight the need to consider the presence of proteins when assessing biological activities of polyphenols in vitro and that enzyme inhibitory activity may be decreased, while the antioxidant capacity remains or even increases.

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Funding agency

Fundação para a Ciência e a Tecnologia

Funding programme

3599-PPCDT

Funding Award Number

PEst-OE/QUI/UI0612/2013

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