RESUMEN
BACKGROUND: Inonotus obliquus, also known as Chaga, is a parasitic fungus growing on birches and used in traditional medicine (especially by Khanty people) to treat various health problems. In this study, we aimed to quantify the 3 metabolites frequently cited in literature, that is, betulin, betulinic acid, and inotodiol in the Chaga recently discovered in forests located in Normandy (France), and to compare their concentrations with Ukrainian and Canadian Chaga. This study also explores the cytotoxicity of the French Chaga against cancer-derived cells and transformed cells. METHODS: A quantification method by HPLC-MS-MS (high-performance liquid chromatography-tandem mass spectrometry) of betulin, betulinic acid, and inotodiol was developed to study the French Chaga and compare the concentration of these metabolites with extracts provided from Chaga growing in Canada and Ukraine. This method was also used to identify and quantify those 3 compounds in other traditional preparations of Chaga (aqueous extract, infusion, and decoction). Among these preparations, the aqueous extract that contains betulin, betulinic acid, and inotodiol was chosen to evaluate and compare its cytotoxic activity toward human lung adenocarcinoma cells (A549 line) and human bronchial epithelial cells (BEAS-2B line). RESULTS: French Chaga contains betulin and betulinic acid at higher levels than in other Chaga, whereas the concentration of inotodiol is greater in the Canadian Chaga. Moreover, the results highlighted a cytotoxic activity of the Chaga's aqueous extract after 48 and 72 hours of exposure with a higher effect on cancer-derived cells A549 than on normal transformed cells BEAS-2B ( P = 0.025 after 48 hours of exposure and P = 0.004 after 72 hours of exposure).
Asunto(s)
Adenocarcinoma del Pulmón/patología , Bronquios/efectos de los fármacos , Citotoxinas/aislamiento & purificación , Citotoxinas/farmacología , Células Epiteliales/efectos de los fármacos , Neoplasias Pulmonares/patología , Poria/química , Células A549 , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Bronquios/patología , Extractos Celulares/química , Extractos Celulares/aislamiento & purificación , Extractos Celulares/farmacología , Extractos Celulares/uso terapéutico , Células Cultivadas , Citotoxinas/uso terapéutico , Ensayos de Selección de Medicamentos Antitumorales , Células Epiteliales/fisiología , Humanos , Oncología Médica/métodos , Oncología Médica/tendencias , Medicina Tradicional/métodos , Polyporus/química , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/patologíaRESUMEN
PURPOSE: Measurement of cerebral blood flow is routinely used to locate the areas involved in generation and spread of seizures in epilepsy patients. Because the nature of the hyperperfused regions varies with the timing of injection of tracer, in this study, we used a rat model of maximal electroshock seizures to follow up the time-dependent changes in the distribution of seizure-induced cerebral blood flow (CBF) changes. METHODS: CBF was measured by the quantitative autoradiographic [14C]iodoantipyrine technique over a 30-s duration. The tracer was injected either at 15 s before seizure induction, simultaneous with the application of the electroshock (tonic phase), at the onset of the clonic phase, or at 3 and 6 min after the seizure (postictal phase). RESULTS: Rates of CBF underwent dynamic changes during the different phases of seizure activity and largely increased over control levels (< or =400%) in the 45 regions studied during all phases of the seizure (first 3 times). CBF remained higher than control levels in 35 and 15 areas at 3 and 6 min after the seizure, respectively. CONCLUSIONS: The distribution of maximal CBF increases showed a good correlation with their known involvement in the circuits underlying the clinical expression of the different types of seizure activity, tonic versus clonic.