Asunto(s)
Betacoronavirus/patogenicidad , Calostro/química , Infecciones por Coronavirus/inmunología , Leche Humana/química , Neumonía Viral/inmunología , Proteoma/genética , Adulto , Animales , Lactancia Materna , COVID-19 , Estudios de Casos y Controles , Cesárea , Calostro/inmunología , Calostro/virología , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/virología , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Humanos , Recién Nacido , Lipidómica , Metaboloma/inmunología , Proteínas de la Leche/clasificación , Proteínas de la Leche/genética , Proteínas de la Leche/inmunología , Leche Humana/inmunología , Leche Humana/virología , Pandemias , Neumonía Viral/genética , Neumonía Viral/virología , Periodo Posparto , Embarazo , Proteoma/clasificación , Proteoma/inmunología , SARS-CoV-2RESUMEN
Ma-Zi-Ren-Wan (MZRW) is a classic Chinese formula which has been used to treat human constipation in China for over 2000 years. In order to make good and rational use of this formula in the future, this paper presents the first attempt to track the pharmacokinetic features of MZRW in rat using rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Ten chemical components of MZRW, namely, rhein, emodin, aloe emodin, hesperidin, naringin, amygdalin, albiflorin, paeoniflorin, magnolol and honokiol, were simultaneously determined in rat plasma after a single oral administration (10g/kg body weight) of MZRW to rats. Geniposide and liquiritin were used as internal standards. The separation was performed on a Waters ACQUITY BEH C18 column (100mm×2.1mm, 1.7µm). The detection was conducted by multiple-reaction monitoring (MRM) in negative ionization mode. Two highest abundant MRM transitions without interference were optimized for each analyte. This method was well validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves had good linearity (r(2)>0.995) over the concentration range from 3.9 to 125.0ng/mL for emodin, 3.9-500.0ng/mL for amygdalin, 2.0-4000.0ng/mL for naringin and hesperidin, 3.9-2000.0ng/mL for magnolol, 7.8-2000.0ng/mL for rhein and 3.9-4000.0ng/mL for albiflorin, paeoniflorin, aloe emodin and honokiol. The intra-day and inter-day precision (relative standard deviation) was within 15%, the accuracy (relative error) ranged from -13.6% to 15.1%, and the lower limit of quantification in plasma ranged between 2.0ng/mL and 7.8ng/mL. Extraction recovery, matrix effect and stability were satisfactory. The validated method was successfully applied to a pharmacokinetic study of these ten compounds after oral administration of MZRW to rats. The pharmacokinetic parameters of each compound can facilitate clinical studies in the future.
Asunto(s)
Antraquinonas/sangre , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/farmacocinética , Flavonoides/sangre , Glicósidos/sangre , Espectrometría de Masas en Tándem/métodos , Animales , Antraquinonas/química , Antraquinonas/farmacocinética , Compuestos de Bifenilo , Medicamentos Herbarios Chinos/administración & dosificación , Flavonoides/química , Flavonoides/farmacocinética , Glicósidos/química , Glicósidos/farmacocinética , Lignanos , Modelos Lineales , Masculino , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The Akt/mTORC1 pathway plays a central role in the activation of Warburg effect in cancer. Here, we present for the first time that halofuginone (HF) treatment inhibits colorectal cancer (CRC) growth both in vitro and in vivo through regulation of Akt/mTORC1 signaling pathway. Halofuginone treatment of human CRC cells inhibited cell proliferation, induced the generation of reactive oxygen species and apoptosis. As expected, reduced level of NADPH was also observed, at least in part due to inactivation of glucose-6-phosphate dehydrogenase in pentose phosphate pathway upon HF treatment. Given these findings, we further investigated metabolic regulation of HF through Akt/mTORC1-mediated aerobic glycolysis and found that HF downregulated Akt/mTORC1 signaling pathway. Moreover, metabolomics delineated the slower rates in both glycolytic flux and glucose-derived tricarboxylic acid cycle flux. Meanwhile, both glucose transporter GLUT1 and hexokinase-2 in glycolysis were suppressed in CRC cells upon HF treatment, to support our notion that HF regulates Akt/mTORC1 signaling pathway to dampen glucose uptake and glycolysis in CRC cells. Furthermore, HF retarded tumor growth in nude mice inoculated with HCT116 cells, showing the anticancer activity of HF through metabolic regulation of Akt/mTORC1 in CRC.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Glucosa/metabolismo , Complejos Multiproteicos/metabolismo , Piperidinas/química , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quinazolinonas/química , Serina-Treonina Quinasas TOR/metabolismo , Animales , Antineoplásicos/química , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Femenino , Transportador de Glucosa de Tipo 1/metabolismo , Glucólisis , Células HCT116 , Hexoquinasa/metabolismo , Humanos , Etiquetado Corte-Fin in Situ , Lípidos/química , Diana Mecanicista del Complejo 1 de la Rapamicina , Medicina Tradicional China , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Vía de Pentosa Fosfato , Inhibidores de la Síntesis de la Proteína/química , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: To recognize changes in the contents of ingredients of Andrographis Tablet in the process of production. METHOD: Adopting TLCS, TLC, HPLC to detect effective contents of ingredients which are produced in every stage of process of Andrographis Table's production. RESULT: Handling with the fresh Herba Andrographis according to current pharmacopeoia's technology, it showed that only dehyandrographolide can be detected. It indicated that the main factor that leads to chemical change is the heating process in the process of production. CONCLUSION: Avoiding heating treatment or reducing heating treatment time is the main factor to protect the effective ingredients.