Navegando por Palavras-chave "Monoterpene"

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    Avaliação da atividade antitumoral do monoterpeno Citronelal na linhagem celular de melanoma humano A2058
    (Universidade Federal de São Paulo, 2021-02-22) Dias, Sofia Munaro [UNIFESP]; Machado Junior, Joel [UNIFESP]; http://lattes.cnpq.br/9553817608522335; http://lattes.cnpq.br/9553817608522335
    O melanoma é um tipo de câncer de pele que tem origem nos melanócitos devido ao acúmulo de mutações em genes que regulam diferentes etapas do processo tumorigênico como sobrevivência, proliferação, migração e invasão. A terapia do melanoma baseia-se na ressecção cirúrgica do tumor, radioterapia, quimioterapia ou imunoterapia. Diversos compostos derivados de fontes naturais, como plantas, já são utilizados no tratamento contra o câncer. Particularmente os terpenóides, que compreendem uma família de compostos naturais com grande variedade química e estrutural devido à quantidade de isoprenos na sua molécula, tem se mostrado efetivo no controle da proliferação e sobrevivência celular em diferentes tipos de câncer, evidenciando seu potencial como agente antitumoral. Entretanto, pouco se sabe sobre o efeito desses compostos em tumores altamente metastáticos como melanomas que apresentam mutações nos genes B-RAFV600E e PTEN, os quais conferem resistência a terapias convencionais. Nesse sentido, o objetivo deste trabalho foi avaliar o potencial antitumoral do monoterpeno Citronelal, extraído e purificado a partir de constituintes do óleo essencial das folhas da espécie vegetal Lippia Alba, na linhagem celular de melanoma humano A2058 que apresenta mutações em B-RAFV600E e PTEN. Nossos resultados mostraram que o Citronelal: 1) inibiu a viabilidade das células A2058 de forma concentração e tempo dependente, avaliado por ensaios de MTT; 2) Induziu apoptose de forma concentração dependente, avaliado por ensaios de anexina V; 3) inibiu a capacidade de migração das células A2058 sugerindo um efeito inibitório em uma etapa importante do processo metastático, avaliado por ensaios de wound healing; 4) inibiu a atividade da quinase AKT, mas não da quinase ERK, componentes de vias de sinalização que regulam sobrevivência, proliferação e migração celular. Juntos nossos dados mostraram que o Citronelal apresenta efeito inibitório in vitro na regulação de importantes eventos celulares, sugerindo uma atividade antitumoral potencial em melanomas.
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    Avaliação dos efeitos dos constituintes de óleos essenciais (timol, carvacrol e p-cimeno) na inflamação pulmonar aguda induzida por instilação de LPS em camundongos
    (Universidade Federal de São Paulo, 2015-05-05) Guerreiro, Marina Pinheiro [UNIFESP]; Prado, Carla Maximo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The acute respiratory distress syndrome (ARDS) is characterized by a diffuse inflammatory response, due to activation of pro-inflammatory agents and oxidants. Despite the high mortality, which affects 40% of patients, there are no specific therapeutic tool for the treatment, which is still based in protective ventilation and in the treatment of the underlying disease and the use of corticosteroids. Extensive research and the elucidation of the mechanisms involved in compounds extracted from plants have been great scientific interest, since many biological effects are shown related to the treatment with medicinal pants. Aim: 1. To evaluate the effects of treatment with thymol, carvacrol and p-cymene, monoterpenes, derived from essential oils of Lippia gracillis e L. sidoides plants, in respiratory mechanics and pulmonary histopathology in an experimental model of acute lung injury (ALI); 2. To evaluate if the presence and/or the position of hydroxyl radical in the chemical structure interferes in the bioactivity of these compounds in the model studied. Methods: Male Balb/c mice received LPS or saline intratracheally. After 6 hours of instillation, animals were treated with thymol, carvacrol, p-cymene (doses of 10, 15 and 20 mg / kg intranasal), dexamethasone (5 mg / kg intraperitoneally) or vehicle. After 24 hours from the time of LPS instillation we evaluated: the respiratory mechanics; inflammatory cells in the bronchoalveolar lavage (Bhavnani and Ballow) and peripheral blood, and total protein levels and proinflammatory cytokines in BALF, isoprostane, NF-?B, and the amount of collagen fibers in the lung tissue. Results: We show first that 6 hours after instillation of LPS, the animals had increased pulmonary inflammation compared to the control, and that this response increased in 24 hours, however changes in lung mechanics occurred only in 24 hours. Then we determined by means of a dose response curve, that 20mg/Kg was the most effective dose for the reduction of neutrophils for the three compounds evaluated. We observed that treatment with the three components of essential oils improved the respiratory function, reduced the amount of inflammatory cells in peripheral blood and BALF. Moreover, these treatments reduced the total protein content, IL-8 and IL-6 in BALF, the amount of collagen fibers and in the positive area of isoprostane in lung tissue. The cytokine IL-1? was not reduced by p-cymene compound and none of the compounds altered the levels of TNF-?. Moreover, thymol and carvacrol significantly reduced expression of P-65-NF-?B in the lung. These results were similar to those obtained with treatment with dexamethasone. Conclusion: Thymol and Carvacrol showed anti-inflammatory effect in a model of ALI, reducing pro-inflammatory cytokines, oxidative stress and inhibiting the activation of p-65-NF-?B, suggesting that the position of the hydroxyl group in the chemical structure does not interfere with the biological effect in this experimental model. Although the p-cymene compound, which has no hydroxyl group in its chemical structure, has reduced lung inflammation and oxidative stress, the mechanisms involved were different from those observed in thymol and carvacrol, since it had no effect on the expression of NF -?B and levels of IL-1? in lung. Together our results suggest that these compounds have significant therapeutic interest to treat inflammatory lung diseases, particularly ARDS and further studies are needed to clarify the exactly mechanisms of action and the importance of the hydroxyl in its structure.
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    The Potential of Secondary Metabolites from Plants as Drugs or Leads Against Protozoan Neglected Diseases - Part I
    (Bentham Science Publ Ltd, 2012-05-01) Schmidt, Thomas J.; Khalid, S. A.; Romanha, Álvaro José; Alves, Tânia Maria de Almeida; Biavatti, Maique Weber; Brun, Reto; Costa, Fernando Batista da; Castro, Solange Lisboa de; Ferreira, Vitor Francisco; Lacerda, Marcus Vinícius Guimarães de; Lago, Joao Henrique Ghilardi [UNIFESP]; Leon, Leonor Laura Pinto; Lopes, Norberto Peporine; Amorim, Rodrigo César das Neves; Niehues, Michael; Ogungbe, Ifedayo Victor; Pohlit, Adrian Martin; Scotti, Marcus Tullius; Setzer, William Nathan; Soeiro, Maria de Nazaré Correia; Steindel, Mário; Tempone, Andre Gustavo [UNIFESP]; Univ Munster; Universidade Federal de Santa Catarina (UFSC); Fiocruz MS; Univ Basel; Swiss Trop & Publ Hlth Inst STPH; Universidade de São Paulo (USP); Fundacao Oswaldo Cruz; Universidade Federal Fluminense (UFF); Fundacao Med Trop Heitor Vieira Dourado; Universidade Federal de São Paulo (UNIFESP); Inst Nacl de Pesquisas da Amazonia; Univ Alabama; Univ Fed Paraiba; Adolfo Lutz Inst
    Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen Neglected Tropical Diseases (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs.The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need.Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.