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Abstract(s)
Com o envelhecimento da população e a pandemia da Covid-19, as doenças
neurodegenerativas e neuropsiquiátricas têm ganho extrema relevância nas sociedades
ocidentais. Apesar de existirem medicamentos para o tratamento destas doenças, estes
apenas contribuem para uma atenuação dos sintomas. Desta forma, não existe ainda cura
para estas doenças, sendo necessário encontrar alternativas às terapêuticas existentes. A
natureza, e as plantas medicinais em particular, são uma excelente fonte de compostos
bioativos. De maneira que se possa estudar o potencial de plantas medicinais como as da
família das Labiadas (Lamiaceae), esta tese teve como objetivo produzir extratos aquosos
e testar a sua bioatividade, focando no stress oxidativo e inibição de enzimas do sistema
nervoso central envolvidas na patogénese da doença de Alzheimer, doença de Parkinson
e depressão. O estudo incidiu nas propriedades neuroprotetoras destes extratos, de forma
a explorar o seu uso futuro na prevenção e tratamento destas doenças.
Como primeira abordagem, determinou-se o conteúdo fenólico total (TPC) e sequestro
de radicais ABTS●+ e DPPH●
para extratos preparados a partir de 16 espécies diferentes
de Lamiaceae. O valor mais alto de TPC foi obtido para a espécie da Salvia officinalis L.
(373,98±15,98 mg GAE/g peso seco). Para o sequestro dos radicais ABTS●+ e DPPH●,
foram as espécies Origanum vulgare L. e Thymus pulegioides que se destacaram com
baixos valores de IC50, ou seja, são inibidores moderados destes radicais.
Para os ensaios posteriores selecionaram-se 5 espécies das 16, que incluiu o Hyssopus
officinalis L., a Leonurus cardiaca L., a Mentha aquatica var. citrata L., a Satureja
montana L. e o Thymus pulegioides L., sendo que estas espécies obtiveram bons
resultados nos ensaios de sequestro dos radicais superóxido e óxido nítrico. No entanto
os extratos aquosos não possuem uma forte atividade inibitória contra as enzimas
acetilcolinesterase (AChE), butirilcolinesterase (BuChE), tirosinase, monoamina oxidase
A (MAO-A) e monoamina oxidase B (MAO-B). A composição química destes 5 extratos
foi analisada por HPLC-DAD, destacando-se a presença de ácidos hidroxicinâmicos, nomeadamente o ácido cafeico e o ácido rosmarínico, e alguns flavonoides.
Nos ensaios de viabilidade celular com células endoteliais, neuroblastoma humano e
fibroblastos, os extratos provaram não ser tóxicos mas, em alguns concentrações,
originavam uma ligeira proliferação celular. Uma vez que os extratos não se mostraram citotóxicos, como trabalho futuro, poder-se iam testar estes extratos noutros alvos terapêuticos relacionados com neurodegeneração.
With the aging of the population and the Covid-19 pandemic, neurodegenerative and neuropsychiatric diseases have gained extreme relevance in Western societies. Although there are medications for the treatment of these diseases, they only contribute to attenuating the symptoms. Thus, there is still no cure for these diseases, and it is necessary to find alternatives to existing therapies. Nature, and medicinal plants, in particular, are excellent sources of bioactive compounds. In order to study the potential of medicinal plants such as those of the Mint family (Lamiaceae), the goal of this thesis is to produce aqueous extracts and test their bioactivity, focusing on oxidative stress and inhibition of enzymes of the central nervous system involved in the pathogenesis of Alzheimer’s disease, Parkinson’s disease and depression. The study focused on the neuroprotective properties of these extracts to explore their future use in the prevention and treatment of these diseases. As a first approach, the total phenolic content (TPC) and the ability to scavenge two different radicals (ABTS●+ and DPPH● ) were determined for the extracts prepared from 16 different species of Lamiaceae. The highest TPC result was obtained for Salvia officinalis L. (373.98±15.98 mg GAE/g dry weight), while Origanum vulgare L. e Thymus pulegioides displayed low IC50 values for radical scavenging activity, considered moderated inibitors of those radicals. After that, only 5 out of 16 extracts were selected for further investigation, including, Hyssopus officinalis L., Leonurus cardiaca L., Mentha aquatica var. citrata L., Satureja montana L. and Thymus pulegioides L. These selected species demonstrated promising outcomes in superoxide and nitric oxide radical scavenging tests. However, when it came to inhibiting enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), tyrosinase, monoamine oxidase A (MAO-A), and monoamine oxidase B (MAO-B), the aqueous extracts did not exhibit strong inhibitory activity. The chemical composition of these 5 extracts was analysed by HPLC-DAD, with hydroxycinnamic acids (namely, caffeic and rosmarinic acids) and flavonoids being detected. In cell viability assessments involving endothelial cells, human neuroblastoma, and fibroblasts, the extracts were found to be non-toxic. However, in certain concentration, they slightly triggered cell proliferation. Since these extracts seem to be non-toxic, future work could focus on testing these extracts in other neurodegeneration related targets.
With the aging of the population and the Covid-19 pandemic, neurodegenerative and neuropsychiatric diseases have gained extreme relevance in Western societies. Although there are medications for the treatment of these diseases, they only contribute to attenuating the symptoms. Thus, there is still no cure for these diseases, and it is necessary to find alternatives to existing therapies. Nature, and medicinal plants, in particular, are excellent sources of bioactive compounds. In order to study the potential of medicinal plants such as those of the Mint family (Lamiaceae), the goal of this thesis is to produce aqueous extracts and test their bioactivity, focusing on oxidative stress and inhibition of enzymes of the central nervous system involved in the pathogenesis of Alzheimer’s disease, Parkinson’s disease and depression. The study focused on the neuroprotective properties of these extracts to explore their future use in the prevention and treatment of these diseases. As a first approach, the total phenolic content (TPC) and the ability to scavenge two different radicals (ABTS●+ and DPPH● ) were determined for the extracts prepared from 16 different species of Lamiaceae. The highest TPC result was obtained for Salvia officinalis L. (373.98±15.98 mg GAE/g dry weight), while Origanum vulgare L. e Thymus pulegioides displayed low IC50 values for radical scavenging activity, considered moderated inibitors of those radicals. After that, only 5 out of 16 extracts were selected for further investigation, including, Hyssopus officinalis L., Leonurus cardiaca L., Mentha aquatica var. citrata L., Satureja montana L. and Thymus pulegioides L. These selected species demonstrated promising outcomes in superoxide and nitric oxide radical scavenging tests. However, when it came to inhibiting enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), tyrosinase, monoamine oxidase A (MAO-A), and monoamine oxidase B (MAO-B), the aqueous extracts did not exhibit strong inhibitory activity. The chemical composition of these 5 extracts was analysed by HPLC-DAD, with hydroxycinnamic acids (namely, caffeic and rosmarinic acids) and flavonoids being detected. In cell viability assessments involving endothelial cells, human neuroblastoma, and fibroblasts, the extracts were found to be non-toxic. However, in certain concentration, they slightly triggered cell proliferation. Since these extracts seem to be non-toxic, future work could focus on testing these extracts in other neurodegeneration related targets.
Description
Keywords
Endothelial cells neuroblastoma fibroblasts cholinesterases monoamine oxidase medicinal plants oxidative stress tyrosinase antioxidant radicals phenolic compounds