Browsing by Author "Fernandes, Adelaide"
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- An in vivo model of ischemic stroke to study potential pharmacological targetsPublication . Mendes, Priscila; Solas, João; Santos, Sofia; Fernandes, Adelaide; Ratilal, Bernardo; Mateus, Vanessa; Rocha, JoãoBackground: Ischemic Stroke (IS) is caused by a focal disruption in cerebral blood flow due to the occlusion of a blood vessel, most commonly the middle cerebral artery (MCA)—the ischemic cascade results in neuronal death and inflammatory response, including in situ microglia activation. Inflammation is a double‐edged sword; it can cause tissue injury but can also help in the tissue repair of the brain. The only approved pharmacological treatment for IS has strong limitations of use depending on the time post-stroke onset. Despite the efforts to develop neuroprotective agents, none have proven efficacious for the human population. Aim: The aim is to clarify the cerebral cellular behavior during the different phases of ischemia-reperfusion as it might contribute to increasing pharmacological targets toward neuroprotection. Methods: The middle cerebral artery occlusion (MCAO) in vivo model was developed (n=8). Rats were randomly divided into two groups: 1) Animals exposed to 1h of ischemia (I1h) and 2) Animals exposed to 1h of ischemia followed by 1h of reperfusion (I/R1h). Brains were collected and the expression of synaptic markers (PSD-95, Syn), inflammatory mediators (TNF-α, IL-1β, IL-10), markers of microglia (Iba1, iNOS, Arg), and astrocytes (GFAP, S100B) were determined by qRealTime-PCR and Western Blot. Results: We found decreased PSD-95 and Syn expression in the ipsilateral hemisphere of both groups (~0.5 fold-I 1h; ~0.5 fold-I/R 1h), compared to the contralateral hemisphere. Levels of IL-10 were decreased in the ipsilateral hemisphere of both groups (~0.2 fold-I 1h; ~0.4 fold-I/R 1h), compared to the contralateral hemisphere. TNF-α was higher in the I/R 1h group compared to the I 1h group. Iba1 and GFAP expression were reduced in the ipsilateral hemisphere of the I/R 1h group (~0.4 fold and 0.8 fold, respectively). Conclusions: Our results strengthen the MCAO rodent model as a potential model to study neuroinflammation as a pharmacological target. Further research is needed to clarify time-dependent changes.
- 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 TNBS-induced 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 vitro assays and administration of the extract in a rat model of carrageenan-induced paw edema 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. 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 recognized 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.