Browsing by Author "Direito, Rosa"
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- Actinic keratosis treated by topical Aloe barbadensis Mill. (Aloe Vera) leaf gelPublication . Direito, Rosa; Ferreira, João Boavida; Ferreira, Ricardo Boavida; Lima, AnaAloe vera is a cactus-resembling, succulent, watery plant, extensively used by the cosmetic and food industries[1]. Actinic keratosis, a dysplastic skin lesion commonly found in low Fitzpatrick skin type individuals[2] associated with chronic UV exposure[3,4], is defined by a scaly, keratotic or pigmented papule on an erythematous base[5]. The precursor to skin field cancerization is actinic keratosis, which is an area of photodamaged skin containing subclinical genetic changes, a direct consequence of intraepithelial UV-induced damage[6,7]. Actinic keratosis, as a precancerous lesion, can develop into an invasive squamous cell carcinoma (ISCC)[6]. There is no way to predict which lesions will progress to ISCC, with guidelines recommending treatment of all actinic keratosis lesions[8- 11]. Field-directed therapies are used to treat multiple actinic keratosis lesions and contiguous field cancerization subclinical lesions[12]
- Avaliação do papel do extrato de diospyros kaki L. : (diospiro) na prevenção da inflamação e cancroPublication . Direito, Rosa; Figueira, Maria Eduardo da Costa Morgado, 1959-; Bronze, Maria do Rosário, 1962-Vários estudos têm mostrado que os processos oxidativos e inflamatórios estão fortemente implicados na etiologia das doenças crónicas. A ingestão de frutos e produtos hortícolas, fontes de vitaminas e compostos fenólicos (CF) com ações antioxidantes e outras, podem ter um papel primordial na proteção da saúde e prevenção da doença. O dióspiro (Diospyros kaki L.) é um fruto rico em CF especialmente proantocianidinas. O objetivo deste trabalho é caracterizar quimicamente o extrato de dióspiro, em especial a sua composição fenólica, averiguar as suas atividades antioxidante, antiinflamatória e antiproliferativa e ainda preparar uma formulação farmacêutica oral deste extrato. A caracterização química do extrato por HPLC-DAD-MS/MS mostrou a sua riqueza em glucose e frutose, L-triptofano e ácidos málico e cítrico. Foram ainda identificados ácidos fenólicos benzóicos e derivados do ácido gálhico e do ácido vanílico bem como procianidinas e flavanóis, derivados glicosilados de flavonas e derivado de flavonol. A atividade antioxidante do extrato avaliada por ensaios de ORAC e HORAC é menor que a de alguns frutos vermelhos mas superiores à de maçãs e morangos. Os ensaios de CAA e burst oxidativo dos neutrófilos mostraram atividade antioxidante superior à das laranjas, peras ou maçãs. A dose oral de extrato de 15mg EAG/Kg mostrou atividade anti-inflamatória em modelo animal de inflamação aguda (edema da pata induzido pela carragenina) e nos modelos animais de inflamação crónica de artrite reumatóide e de colite ulcerosa. O extrato fenólico de dióspiro reduziu a invasão e proliferação de células de adenocarcinoma do cólon HT-29 e inibiu ligeiramente as atividades de MMPs com efeito dependente da dose. Os fitossomas com extrato, de dimensão inferior a 300nm, conseguem encapsular 97,4% do total de CF e são monodispersos e com potencial zeta negativo e apresentam maior atividade antioxidante durante 6 meses sob condições de armazenamento de T e RH estabelecidas do que o extrato livre. Assim, o extrato fenólico de dióspiro mostrou propriedades antioxidantes, antiinflamatórias e efeito anti-proliferativo nas células de cancro de cólon. A incorporação em fitossomas é uma alternativa para produção de suplemento alimentar.
- Lupinus albus protein componentes inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivoPublication . Mota, Joana; Direito, Rosa; Rocha, João; Fernandes, João; Sepodes, Bruno; Figueira, Maria Eduardo; Raymundo, Anabela; Lima, Ana; Ferreira, Ricardo BoavidaMatrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are regarded as important clinical targets due to their nodal-point role in inflammatory and oncological diseases. Here, we aimed at isolating and characterizing am MMP-2 and-9 inhibitor (MMPI) from Lupinus albus and at assessing its efficacy in vitro and in vivo. The protein was isolated using chromatographic and 2-D electrophoretic procedures and sequenced by using MALDI-TOF TOF and MS/MS analysis. In vitro MMP-2 and 9 inhibitions were determined on colon adenocarcinoma (HT29) cells, as well as by measuring the expression levels of genes related to these enzymes. Inhibitory activities were also confirmed in vivo using a model of experimental TNBS-induced colitis in mice, with oral administrations of 15 mg kg1. After chromatographic and electrophoretic isolation, the L. albus MMP-9 inhibitor was found to comprise a large fragment from -conglutin and, to a lower extent, small fragments of -conglutin. In vitro studies showed that the MMPI successfully inhibited MMP-9 activity in a dose-dependent manner in colon cancer cells, with an IC50 of 10 g mL1 without impairing gene expression nor cell growth. In vivo studies showed that the MMPI maintained its bioactivities when administered orally and significantly reduced colitis symptoms, along with a very significant inhibition of MMP-2 and -9 activities. Overall, results reveal a novel type of MMPI in lupine that is edible, proteinaceous in nature and soluble in water, and effective in vivo, suggesting a high potential application as a nutraceutical or a functional food in pathologies related to abnormally high MMP-9 activity in the digestive system
- Reduction of inflammation and colon injury by a Pennyroyal phenolic extract in experimental inflammatory bowel disease in micePublication . Rocha, João; Direito, Rosa; Lima, Ana; Mota, Joana; Gonçalves, Margarida; Duarte, Maria Paula; Solas, João; Peniche, Bruno Felício; Fernandes, Adelaide; Pinto, Rui; Ferreira, Ricardo Boavida; Sepodes, Bruno; Figueira, Maria-EduardoPurpose: Little is known about the pharmacological effects of the phenolic compounds of Pennyroyal (Mentha pulegium). This Mediterranean aromatic plant, used as a gastronomic spice and as food preservative by the food industry has been studied mainly due to its essential oil antibacterial properties, composed primarily by monoterpenes. With this work, we aimed to evaluate the effects of a phenolic extract of pennyroyal in the impairment of inflammatory processes in Inflammatory Bowel Diseases (IBD) and in the potential inhibition of progression to colorectal cancer (CRC). Methods: To that purpose, we evaluated the effect of pennyroyal extract administration in a model of TNBSinduced colitis in mice and further determined its effect on human colon carcinoma cell proliferation and invasion. Results: The phenolic extract of pennyroyal exhibited antioxidant properties in in vitro assays and administration of the extract in a rat model of carrageenan-induced paw oedema led to significant anti-inflammatory effects. Further results evidenced a beneficial effect of the phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells, effects not previously described, to our knowledge. A reduction in several markers of colon inflammation was observed following administration of the extract to colitis-induced mice, including functional and histological indicators. A successful inhibition of cancer cell invasion and proliferation was also observed in in vitro studies with HT-29 cells. Furthermore, the extract also led to a reduced expression of iNOS/COX-2 in the colon of colitis-induced mice, both being crucial mediators of intestinal inflammation. Conclusions: Taking into consideration the central role of inflammation in the pathophysiology of CRC and the recognised connection between inflammatory events and cancer, these results enlighten the relevance of the phenolic constituents of pennyroyal as important pharmacological sources in the investigation of new treatment options for patients with inflammatory bowel diseases