Reduction of inflammation and colon injury by a Pennyroyal phenolic extract in experimental inflammatory bowel disease in mice

Purpose: 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 diseasesinfo:eu-repo/semantics/publishedVersio

3D printing combined with continuous flow for chemical synthesis

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019A química de fluxo contínuo tem vindo a ganhar relevância e interesse tanto por parte de investigadores como da indústria. O advento desta nova forma de fazer química deve-se às inúmeras vantagens que esta técnica traz face à produção tradicional. Surge então uma pergunta óbvia, o porquê desta técnica não estar mais difundida quer a nível investigacional quer no meio industrial. Tal deve-se ao seu custo, sobretudo a nível dos laboratórios de investigação. Aproveitando a boleia da nova revolução industrial, onde a impressão 3D surge como uma das novas tecnologias promissoras, a química de fluxo contínuo tem o caminho facilitado para passar de uma tecnologia promissora a uma tecnologia predominante. Utilizando a impressão 3D, desenvolveu-se um sistema de fluxo contínuo de baixo custo e tamanho reduzido, pronto a utilizar em qualquer laboratório de investigação. A sua mais valia foi avaliada sob duas formas: medição do fluxo de modo a avaliar o funcionamento do sistema, especialmente a nível da sua consistência e capacidade de trabalhar em diferentes condições, e realização de diferentes reações químicas de modo a demostrar a utilidade do sistema. Na medição dos fluxos, obtiveram-se fluxos precisos e em concordância com a lei de Hagen-Poiseuille até certo ponto. Tais resultados mantiveram-se quando aumentada a temperatura até um certo limite. No entanto, conseguiu-se sempre trabalhar com temperaturas superiores às dos pontos de ebulição dos solventes. A sua utilidade foi demonstrada numa gama de reações SNAr para produzir derivados de éter substituídos, obtendo-se os produtos esperados com bons rendimentos na maioria das reações. A reação de Grignard também foi efetuada de modo a averiguar a utilidade do sistema neste tipo de reação, mas desta vez num reator impresso com outro material para também testar a resistência deste material ao tetraidrofurano. Nesta reação obteve-se o produto esperado com um rendimento bruto elevado. Por último, o trabalho continuou a ser desenvolvido com vista à automação do sistema. Através da programação e utilizando um Arduino conseguiu-se estabelecer as bases para medir a temperatura e pressão in-line e controlar solenoides através de uma equação de modo a injetar no sistema a quantidade pretendida de uma qualquer solução. Esta fase foi um sucesso e culminou com a criação de uma interface no computador que permite o controlo do sistema e visualização dos dados recolhidos pelos sensores in-line.Continuous flow chemistry has gained relevance and interest from both researchers and industry. The advent of this new way of doing chemistry is due to the numerous advantages that this technique brings over batch production. The obvious question then arises. Why this technique isn’t widespread at both the research and industrial levels. This is mainly due to its cost, especially at the level of research laboratories. Taking advantage of the ride of the new industrial revolution, where 3D printing emerges as one of the promising new technologies, continuous-flow chemistry has helped to move from promising to predominant technology. Using 3D printing, it has developed a low-cost, small-footprint and modular continuous-flow system, ready for use in any research laboratory. Its value has been assessed in two ways: flow measurement to assess the system's capacity to work, especially its consistency and ability to perform under different conditions, and different chemical reactions to show the utility of the system. In the flow measurement, accurate flows were obtained and in accordance with the Hagen-Poiseuille law to some extent. Such results were maintained only when the temperature was raised to a certain limit. However, it was always possible to work at temperatures higher than the boiling points of the solvents. Its utility has been demonstrated in a range of SNAr reactions to produce substituted ether derivatives, where the expected products were obtained with good yields in most reactions. The Grignard reaction was also performed to ascertain the usefulness of the system in this type of reaction, but this time in a reactor printed with another material to also test the resistance of this material to tetrahydrofuran. In this reaction, the expected product was obtained with a high crude yield. Finally, work continued to be carried out, aiming for system automation. Through programming and using an Arduino, it was possible to lay the foundations for measuring in-line temperature and pressure and controlling solenoids through an equation to inject the desired amount of any solution into the system. This phase was a success and culminated in the creation of a computer interface that allows system control and visualization of data collected by in-line sensors