Analysis of metabolites of 4,5-dicaffeoylquinic acid in rat plasma and urine based on LC-MS / 中国中药杂志

Ultra high performance liquid chromatography tandem high field orbital trap mass spectrometry(UPLC-Orbitrap Elite-MS/MS) method was applied in this paper to analyze the metabolites of 4,5-dicaffeoylquinic acid in rat plasma and urine after oral administration. A gradient elution was performed by using Thermo C_(18) column(2.1 mm×100 mm, 1.9 μm), with 0.1% formic acid solution-acetonitrile as the mobile phase. Mass spectral data of biological samples were collected in negative ion mode. The data were extracted by Compound Discovery 2.1 software. Then the blank group samples and the drug samples were compared for exact molecular weight and the mass fragmentation information, and the secondary fragment fitting ratio was calculated to finally attribute the metabolites. As a result, 15 metabolites were detected in rat plasma, and 16 metabolites were detected in urine. The involving metabolic reactions included methylation, hydration, dehydration, reduction, glucuronide conjugation, and sulfation reaction. The metabolites in plasma and urine complemented each other and initially revealed the migration and excretion patterns of this compound in the body. A method for pre-processing biological samples, high-resolution LC-MS instrumentation data, and qualitative software was established in this study to identify metabolite structures, laying the foundation for the study of the active ingredients and in vivo pharmacodynamics forms of Chinese medicines.

Metformin mediated reverse cholesterol transport to inhibit atherosclerosis / 中国药理学通报

Aim To investigate the molecular mechanism of metformin inhibiting atherosclerosis in ApoE 1_ mice by reverse cholesterol transport. Methods Eighteen ApoE -/ _ mice were randomly divided into three groups, control group, model group and metformin group, and body weight changes were monitored weekly. Blood samples were taken to measure serum lipid levels; animal ultrasound was used to measure abdominal aortic wall thickness; HE and oil red 0 staining were used to evaluate the degree of liver steatosis; Western blot was used to detect the expression of liver cholesterol reverse transport-related proteins LXRa and ABCA1. Results Compared with control group, the body weight, serum T C, T G, and LDL in model group increased, HDL decreased(P <0. 05), abdominal aortic wall thickened (P <0. 05), liver fat deposition increased, and L X R a, ABCA1 expression was reduced. In metformin group, body weight, serum T C, T G, LDL decreased, HDL increased (P <0. 05), liver fat deposition and abdominal aortic wall thickness were significandy reduced (P <0. 05), and LXRa and ABCA1 expressions markedly increased (P <0. 0 5). Conclusions Metformin can delay the progression of atherosclerosis by up-regulating the expression of liver cholesterol reverse transport related proteins LXRa and ABCA1, enhancing liver reverse cholesterol transport, regulating blood lipid metabolism and reducing liver lipid deposition.