Antifungal activity of Thymus vulgaris L. essential oil and phytoconstituents against Rhizopus oryzae e Rhizopus microsporus: interaction with ergosterol

Mucormycoses are infections that have high rates of morbidity and mortality. They show high resistance to antifungal agents, and there is a limited therapeutic arsenal currently available, therefore, there is a great need to give priority to testing therapeutic agents for the treatment of mucormycosis. Along this line, the use of essential oils and phytoconstituents has been emphasized as a new therapeutic approach. The objective of this work was to investigate the antifungal activity of the essential oil (EO) of Thymus vulgaris, and its constituents thymol and p-cymene against Rhizopus oryzae and Rhizopus microsporus, through microbiological screening, determination of minimal inhibitory concentration (MICs) and minimal fungicidal concentration (MFCs), effects on mycelial growth and germination of sporangiospores, fungal morphology and interaction with ergosterol. Also was evaluated the preclinical acute toxicity in mice. In microbiological screening the T. vulgaris essential oil showed antifungal potential against resistant strains of R. oryzae.The MIC of EO and thymol varied 128 512 μg/mL, but the MFC of EO and thymol varied 512 1024 μg/mL and 128 1024 μg/mL, respectively. The results also showed that EO and thymol significantly inhibited mycelial development and germination of sporangiospores of both species of Rhizopus. Investigation of the mechanism of antifungal action showed that EO and thymol interact with ergosterol. These data indicate that EO of T. vulgaris and thymol possess strong antifungal activity, which can be related to their interaction with ergosterol, supporting the possible use of these products in the treatment of mucormycosis. In preclinical acute toxicology the doses of 125, 250, 500 and 1000 mg/kg intraperitoneally (i.p.) showed depressive activity on the central nervous system (CNS). In addition to these parameters was observed that the doses of 125 and 250 mg/kg did not change the body and organs weight of the animals, but it was observed change some of the hematological parameters of the mice. The EO showed DL50 of 250 mg/kg for male and 459.6 mg/kg for female; however the thymol showed DL50 of 222.3 mg/kg for male and 1551 mg/kg for female. These data indicate that EO of T. vulgaris and thymol possess strong antifungal activity, which can be related to their interaction with ergosterol.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESAs mucormicoses são infecções que possuem elevadas taxas de morbidade e mortalidade, limitado arsenal terapêutico, devido a resistência aos antifúngicos. Portanto, existe uma significativa necessidade de priorizar, testar e aplicar melhorias terapêuticas para o tratamento das mucormicoses. É nesse contexto, que os óleos essenciais e fitoconstituintes vem se destacando como uma nova abordagem terapêutica. O objetivo deste trabalho foi investigar a atividade antifúngica in vitro do óleo essencial (OE) de Thymus vulgaris L. e de seus componentes majoritários (timol e p-cimeno) contra Rhizopus oryzae e Rhizopus microsporus, através da triagem microbiológica, da determinação da concentração inibitória mínima (CIM) e fungicida mínima (CFM), avaliação dos efeitos dos fitoconstituintes no crescimento micelial, na germinação dos esporos fúngicos, na morfologia fúngica e interação com ergosterol. Também foi avaliada a toxicidade pré-clínica aguda em camundongos. Na triagem microbiológica o óleo essencial de T. vulgaris apresentou um dos melhores perfis antifúngicos contra cepas resistentes de R. oryzae. A CIM dos produtos variou entre 128-512 μg/mL, já as CFMs do óleo essencial e timol variaram entre 512-1024 μg/mL e 128-1024 μg/mL, respectivamente. Os resultados também mostraram que tanto o OE como o timol inibiram significativamente o desenvolvimento micelial e a germinação de esporos de ambas as espécies de Rhizopus. Em seguida foi mostrado que os produtos testados alteram a morfologia de R. oryzae e R. microsporus. Na investigação do mecanismo de ação antifúngica foi evidenciado que o OE e o timol interagem com o ergosterol, esterol presente na membrana dos fungos. No ensaio toxicológico pré-clínica agudo, as doses de 125, 250, 500 e 1000 mg/kg via intraperitoneal (i.p.) apresentaram atividade depressora do sistema nervoso central (SNC). Adicionalmente a estes parâmetros foi evidenciado que o OE e o timol nas doses de 125 e 250 mg/kg não promoveram alterações significativas na evolução ponderal e peso dos órgãos dos camundongos. Entretanto, ambas as doses das drogas-teste alteram alguns parâmetros hematológicos dos camundongos. Após 72 h de observação o OE apresentou DL50 estimada em 250 mg/kg para camundongos machos e 459,6 mg/kg para as fêmeas. Já o timol apresentou DL50 estimada em 222,3 mg/kg para os machos e 1551 mg/kg para as fêmeas. Estes dados indicam que o óleo essencial de T. vulgaris e timol, apresentam forte atividade antifúngica, que pode estar relacionada com a interação com ergosterol e consequentemente lise de membrana

Antifungal Activity of Thymus vulgaris L. Essential Oil and Its Constituent Phytochemicals against Rhizopus oryzae: Interaction with Ergosterol

Mucormycoses are emerging infections that have high rates of morbidity and mortality. They show high resistance to antifungal agents, and there is a limited therapeutic arsenal currently available, therefore, there is a great need to give priority to testing therapeutic agents for the treatment of mucormycosis. Along this line, the use of essential oils and phytoconstituents has been emphasized as a new therapeutic approach. The objective of this work was to investigate the antifungal activity of the essential oil (EO) of Thymus vulgaris, and its constituents thymol and p-cymene against Rhizopus oryzae, through microbiological screening, determination of minimal inhibitory concentration (MICs) and minimal fungicidal concentration (MFCs), effects on mycelial growth and germination of sporangiospores and interaction with ergosterol. The MIC of EO and thymol varied 128–512 µg/mL, but the MFC of EO and thymol varied 512–1024 µg/mL and 128–1024 µg/mL, respectively. The results also showed that EO and thymol significantly inhibited mycelial development and germination of sporangiospores. Investigation of the mechanism of antifungal action showed that EO and thymol interact with ergosterol. These data indicate that EO of T. vulgaris and thymol possess strong antifungal activity, which can be related to their interaction with ergosterol, supporting the possible use of these products in the treatment of mucormycosis

Flavonoids with Gastroprotective Activity

Peptic ulcers are a common disorder of the entire gastrointestinal tract that occurs mainly in the stomach and the proximal duodenum. This disease is multifactorial and its treatment faces great difficulties due to the limited effectiveness and severe side effects of the currently available drugs. The use of natural products for the prevention and treatment of different pathologies is continuously expanding throughout the world. This is particularly true with regards to flavonoids, which represent a highly diverse class of secondary metabolites with potentially beneficial human health effects that is widely distributed in the plant kingdom and currently consumed in large amounts in the diet. They display several pharmacological properties in the gastroprotective area, acting as anti-secretory, cytoprotective and antioxidant agents. Besides their action as gastroprotectives, flavonoids also act in healing of gastric ulcers and additionally these polyphenolic compounds can be new alternatives for suppression or modulation of peptic ulcers associated with H. pylori. In this review, we have summarized the literature on ninety-five flavonoids with varying degrees of antiulcerogenic activity, confirming that flavonoids have a therapeutic potential for the more effective treatment of peptic ulcers

Aromatic Plants: use and nutraceutical properties

In the last years it has progressively been observed a substantial increase in the use of aromatic herbs and essential oils. Mediterranean area represents a particular environment in which many constraint factors (high light, temperature, drought, salinity, air pollution, etc.) induce a wide range of secondary metabolites in plants. These compounds can be useful utilized by humans for different applications: antibiotics, antimycotic, animal nutrition, cosmetics, food additives, biorepellents, etc. This paper reviews the literature on recent agro-industrial applications of Mediterranean plant species and medicinal plants used for the treatment of infectious diseases. The review includes accounts of extracts, essential oils and other active principles isolated from plants that have been used by folk medicine as antimicrobial agents. The name and part of the studied plants, spectrum of activity, type of active compounds and methods used are discussed and their mechanisms of action as well