Fexaramine improves non-alcoholic fatty liver disease in mice by stimulating intestinal FXR / 药学学报

Non-alcoholic fatty liver disease (NAFLD) is considered to be a manifestation of metabolic syndrome and has become one of the chronic diseases that endanger health around the world. There is still a lack of effective therapeutic drugs in clinical practice. Farnesoid X receptor (FXR) has been a popular target for NAFLD research in recent years. Fexaramine (Fex) is a potent and selective agonist of FXR, and its mechanism of action to improve NAFLD is unclear. Therefore, in this study, a mouse model of NAFLD was constructed using a high-fat, high-cholesterol diet and treated with Fex orally for 6 weeks. We evaluated the ameliorative effect of Fex on disorders of glucolipid metabolism in NAFLD mice, and preliminarily explored its potential mechanism of action. The animal experiments were approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval number: PZSHUTCM210913011). In this study, it was found that 100 mg·kg-1 Fex significantly inhibited body weight gain, alleviated insulin resistance, improved liver injury and lipid accumulation in NAFLD mice. The effect of Fex on the expression of hepatic intestinal FXR and its target genes in NAFLD mice was further examined. Analysis of serum and hepatic bile acid profiles and expression related to hepatic lipid metabolism. It was found that Fex could stimulate intestinal FXR, promote fibroblast growth factor 15 (FGF15) secretion, inhibit the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), the rate-limiting enzyme of bile acid synthesis in liver, regulate bile acid synthesis by negative feedback, and improve the disorder of bile acid metabolism. At the same time, Fex reduces liver lipid synthesis and absorption, increases fatty acid oxidation, thus improving liver lipid metabolism. This study shows that Fex can improve NAFLD by activating intestinal FXR-FGF15 signal pathway and regulating liver lipid metabolism.

Quality Evaluation of Tremella fuciformis Polysaccharides from Different Sources / 中国实验方剂学杂志

Objective:To establish a method for the determination of polysaccharide and monosaccharide composition of Tremella fuciformis, and to analyze the difference of polysaccharide content in T. fuciformis from different sources and cultivation methods, so as to provide reference for the quality determination.Method:High performance size exclusion chromatography coupled with multi-angle laser light scattering and refractive index detection (HPSEC-MALLS-RID) was employed to determine the content and relative molecular weight distribution of T. fuciformis polysaccharides. The monosaccharide types and proportions of T. fuciformis polysaccharides were analyzed by 1-phenyl-3-methyl-5-pyrazolone (PMP) precolumn derivative high performance liquid chromatography (HPLC).Result:The weight-average relative molecular weight (Mw) and the content of polysaccharides in T. fuciformis cultivated by cut-log from different sources were distributed in 2.618×106-3.503×106 Da and 307.12-609.06 g·kg-1, respectively. These two parameters of polysaccharides in T. fuciformis with substitute cultivation from different sources were 2.723×106-3.886×106 Da and 366.38-647.37 g·kg-1, respectively. The T. fuciformis polysaccharides mainly consisted of mannose, glucuronic acid, glucose, galactose, xylose and fucose, their ratios in samples with cut-log and substitute cultivation were 4.4∶0.7∶1.0∶0.2∶1.4∶1.6 and 4.4∶0.8∶1.0∶0.1∶1.5∶1.5, respectively. The contents of the above six monosaccharides in 39 batches of T. fuciformis from different sources were mannose of 36.71-191.31 g·kg-1, glucose of 10.46-76.10 g·kg-1, galactose of 1.00-6.72 g·kg-1, xylose of 16.73-70.54 g·kg-1, glucuronic acid of 9.74-32.12 g·kg-1, fucose of 17.16-68.20 g·kg-1.Conclusion:The content of polysaccharides in T. fuciformis from different sources has a certain difference, the developed method can be used as a routine method for the quality evaluation of polysaccharides in T. fuciformis.

Regulation of exogenous calcium on photosynthetic system of honeysuckle under salt stress / 中国中药杂志

Exogenous calcium can enhance the resistance of certain plants to abiotic stress. However,the role of calcium insaltstressed honeysuckle is unclear. The study is aimed to investigate the effects of exogenous calcium on the biomass,chlorophyll content,gas exchange parameters and chlorophyll fluorescence of honeysuckle under salt stress. The results showed that the calcium-treated honeysuckle had better photochemical properties than the salt-stressed honeysuckle,such as PIABS,PItotal,which represents the overall activity of photosystemⅡ(PSⅡ),and related parameters for characterizing electron transport efficiency φP0,ψE0,φE0,σR,and φR are significantly improved. At the same time,the gas exchange parameters Gs,Ci,Trare also maintained at a high level. In summary,exogenous calcium protects the activity of PSⅡ,promotes the transmission of photosynthetic electrons,and maintains a high Ci,therefore enhances the resistance of honeysuckle under salt stress.

Effect of calcium on ion contents and expression of photosynthetic related genes in honeysuckle under salt stress / 中国中药杂志

Exogenous calcium can enhance the resistance of certain plants to abiotic stress. Research have demonstrated that exogenous calcium could enhances the resistance of honeysuckle under salt stress by promoting the transmission of photosynthetic electrons.The aim of this study was to investigate the effects of exogenous calcium on the contents of Na~+,K~+,Ca~(2+),Mg~(2+)and the expression of photosynthetic related genes Cab and rbc L. In this study,we used ICP-OES to analysis ion contents and used qRT-PCR to analysis the expression patterns of Cab and rbc L. The results showed that CaCl_2 significantly enhanced the K~+-Na~+,Ca~(2+)-Na~+,Mg~(2+)-Na+ratio of honeysuckle treated with 50 and 100 mmol·L~(-1) NaCl. Meanwhile,Cab and rbc L were significantly up-regulated under short-term salt stress,and CaCl_2 promoted this trend. From the two gene expression patterns,rbc L rapidly up-regulated on the first day of stress and then decreased,and was more sensitive to environmental changes. In summary,exogenous calcium could alleviate salt stress and increase plant development by increasing intracellular K~+-Na~+,Ca~(2+)-Na~+,Mg~(2+)-Na+ratio,and the transient overexpression of Cab and rbc L.

Analysis of paraquat in blood and urine by sodium borohydride/nickel chloride chemical reduction-gas chromatography/thermionic specific detector / 法医学杂志

OBJECTIVE@#To establish a new method for the analysis of paraquat in blood and urine by sodium borohydride/nickel chloride chemical reduction-gas chromatography/thermionic specific detector.@*METHODS@#An initial procedure of precipitation was performed by adding hydrochloric solution with sodium chloride and a mixture of chloroform and ethanol. Then the analyte contained in supernatant was reduced by a reduction system of sodium borohydride and nickel chloride and extracted by acetic ether. Ethyl paraquat (EPQ) was used as internal standard. GC/TSD was used to identify and quantify the analyte.@*RESULTS@#The limits of detection (S/N=3) in blood and urine were 0.002 and 0.004 microg/mL, respectively. The linear ranges were 0.050-30.0 microg/mL. Correlation coefficients in blood and urine were 0.999 and 0.998, respectively. The recoveries exceeded 80% both in blood and urine.@*CONCLUSION@#This method is applicable for quantification of paraquat in biological fluids.

Determination of ketamine and norketamine in blood and urine by high performance liquid chromatography / 法医学杂志

OBJECTIVE@#To develop a high-performance liquid chromatographic method for determination of ketamine and norketamine in blood and urine.@*METHODS@#The compounds were extracted from blood or urine by liquid-liquid extraction using toluene after blood or urine was adjusted pH to 14. The extracts were analyzed by HPLC.@*RESULTS@#Linear limits of ketamine and norketamine determination in blood ranged from 0.05 microg/mL to 10 microg/mL (R2 > 0.9993) and in urine ranged from 0.01 microg/mL to 200 microg/mL (R2 > 0.9995). Limits of detection (LODs) for ketamine and norketamine were 0.006 microg/mL and 0.003 microg/mL (S/N > or = 3), respectively. The mean extraction recovery was over 82.4% and its coefficients of variation were less than 10.0% for ketamine and norketamine. Concentration-time curves and urinary drug velocity curves of ketamine norketamine were obtained by determinations of them in blood and urine in rat using the developed method.@*CONCLUSION@#The method is sensitive, simple, rapid and suitable for determination of ketamine and norketamine in blood and urine for toxicological and clinical pharmaceutical analysis.