RESUMO
Astragaloside IV (AS-IV) has been shown to provide renal protection in various kidney injury models. However, the metabolic profile variation of AS-IV in pathological models in vivo is not well established. This study aims to explore the metabolic pathway of AS-IV in vivo in the classical puromycin aminonucleoside (PAN)-induced kidney injury in a rat model. Twelve Wistar rats were randomly divided into the AS-IV (CA) and the PAN+AS-IV (PA) treatment groups. PAN was injected by a single tail intravenous (i.âv.) injection at 5 mg/100 g body weight, and AS-IV was administered intragastrically (i.âg.) at 40 mg/kg for 10 days. Fecal samples of these rats were collected, and metabolites of AS-IV were detected by ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) to explore the AS-IV metabolic pathway. The metabolic differences between the AS-IV and PAN+AS-IV groups were compared. A total of 25 metabolites were detected, and deglycosylation, deoxygenation, and methyl oxidation were found to be the main metabolic pathways of AS-IV in vivo. The abundance of most of these metabolites in the PAN+AS-IV group was lower than that in the AS-IV treatment group, and differences for seven of them were statistically significant. Our study indicates that AS-IV metabolism is affected in the PAN-induced kidney injury rat model.
Assuntos
Saponinas , Espectrometria de Massas em Tandem , Triterpenos , Ratos , Animais , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Ratos Wistar , PuromicinaRESUMO
Indoleamine 2,3-dioxygenase 1 (IDO1) has been shown to play an important role in the immune escape process of tumors, and therefore is considered as a promising target for tumor immunotherapy. In this study, off-line and on-line capillary electrophoresis methods were developed for IDO1 inhibitors screening from natural product extracts. The optimized separation conditions of CE were achieved with 32 mM sodium tetraborate (pH 9.22) as background electrolyte, using a separation voltage of 21 kV. The off-line CE method was verified by the determination of enzymatic kinetic parameters and inhibitory mechanisms of two known inhibitors. A partial filling on-line CE method combined with rapid polarity switching was used for rapid screening of IDO1 inhibitors. The whole reaction and separation process was completed within 5 min. The on-line CE screening results showed that six of 18 natural products had inhibitory effect on IDO1, namely Carthamus tinctorius, Schisandra chinensis, Raisin, Coffee, Hawthorn and Radix angelicae sinensis. The results of on-line CE experiments were consistent with the off-line results, which proved the practicability and effectiveness of the method for inhibitors screening.
Assuntos
Técnicas de Química Analítica/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Eletroforese Capilar , Inibidores Enzimáticos/isolamento & purificação , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Produtos Biológicos/química , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , HumanosRESUMO
As an ancient Chinese herbal medicine, Panax ginseng C.A. Meyer (P. ginseng) has been used both as food and medicine for nutrient supplements and treatment of human diseases in China for years. Fatigue, as a complex and multi-cause symptom, harms life from all sides. Millions worldwide suffer from fatigue, mainly caused by physical labor, mental stress, and chronic diseases. Multiple medicines, especially P. ginseng, were used for many patients or sub-healthy people who suffer from fatigue as a treatment or healthcare product. This review covers the extract and major components of P. ginseng with the function of anti-fatigue and summarizes the anti-fatigue effect of P. ginseng for different types of fatigue in animal models and clinical studies. In addition, the anti-fatigue mechanism of P. ginseng associated with enhancing energy metabolism, antioxidant and anti-inflammatory activity is discussed.