Gardenia Iridoid Glucosides Protect Against α-Naphthalene Isothiocya-Nate-Induced Cholestatic Rats Through Activation of the FXR-SHP Signaling Pathway.

Introduction: Cholestasis is a common liver disorder that currently has limited treatment options. Gardenia Iridoid Glucosides (GIG) have been found to possess various physiological activities, such as cholagogic, hypoglycemic, antibacterial, and anti-inflammatory effects. The objective of this study was to investigate the effects of GIG on bile acid enterohepatic circulation and explore the underlying mechanism in cholestatic rats. Methods: In order to identify key pathways associated with cholestasis, we conducted Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In vivo experiments were then performed on alpha-naphthylisothiocyanate (ANIT)-treated rats to assess the impact of GIG. We measured bile flow and various biomarkers including total bilirubin (TB), total bile acids (TBA), total cholesterol (TC), malondialdehyde (MDA), glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and total superoxide dismutase (T-SOD) in the serum. We also examined the expression levels of bile salt export pump (BSEP), ATP-binding cassette subfamily B member 4 (ABCB4), far-nesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (CYP7A1), and sodium taurocholate cotransporting polypeptide (NTCP) in liver tissue. In vitro experiments were conducted on primary hepatocytes to further investigate the mechanism of action of GIG on the expression of SHP, CYP7A1, NTCP, and FXR. Results: Our in vivo experiments demonstrated that GIG significantly increased bile flow and reduced the levels of TB, TBA, TC, MDA, GPT, and GOT, while increasing T-SOD levels in ANIT-treated rats. Addi-tionally, GIG ameliorated liver tissue damage induced by ANIT, upregulated the expression of BSEP and ABCB4, and modulated the protein expression of FXR, SHP, CYP7A1, and NTCP in model rats. In vitro experiments further revealed that GIG inhibited the expression of SHP, CYP7A1, and NTCP by suppressing the expression of FXR. Conclusion: This study provides new insights into the therapeutic potential of GIG for the treatment of cholestasis. GIG demonstrated beneficial effects on bile acid enterohepatic circulation and liver biomarkers in cholestatic rats. The modulation of FXR and its downstream targets may contribute to the mechanism of action of GIG. These findings highlight the potential of GIG as a therapeutic intervention for cholangitis.

Characterization of Regional Combustion Efficiency using ΔXCO: ΔXCO2 Observed by a Portable Fourier-Transform Spectrometer at an Urban Site in Beijing.

Measurements of column-averaged dry-air mole fractions of carbon dioxide and carbon monoxide, CO2 (XCO2) and CO (XCO), were performed throughout 2019 at an urban site in Beijing using a compact Fourier Transform Spectrometer (FTS) EM27/SUN. This data set is used to assess the characteristics of combustion-related CO2 emissions of urban Beijing by analyzing the correlated daily anomalies of XCO and XCO2 (e.g., ΔXCO and ΔXCO2). The EM27/SUN measurements were calibrated to a 125HR-FTS at the Xianghe station by an extra EM27/SUN instrument transferred between two sites. The ratio of ΔXCO over ΔXCO2 (ΔXCO:ΔXCO2) is used to estimate the combustion efficiency in the Beijing region. A high correlation coefficient (0.86) between ΔXCO and ΔXCO2 is observed. The CO:CO2 emission ratio estimated from inventories is higher than the observed ΔXCO:ΔXCO2 (10.46 ± 0.11 ppb ppm-1) by 42.54%-101.15%, indicating an underestimation in combustion efficiency in the inventories. Daily ΔXCO:ΔXCO2 are influenced by transportation governed by weather conditions, except for days in summer when the correlation is low due to the terrestrial biotic activity. By convolving the column footprint [ppm (µmol m-2 s-1)-1] generated by the Weather Research and Forecasting-X-Stochastic Time-Inverted Lagrangian Transport models (WRF-X-STILT) with two fossil-fuel emission inventories (the Multi-resolution Emission Inventory for China (MEIC) and the Peking University (PKU) inventory), the observed enhancements of CO2 and CO were used to evaluate the regional emissions. The CO2 emissions appear to be underestimated by 11% and 49% for the MEIC and PKU inventories, respectively, while CO emissions were overestimated by MEIC (30%) and PKU (35%) in the Beijing area.

Brexpiprazole caused glycolipid metabolic disorder by inhibiting GLP1/GLP1R signaling in rats.

Brexpiprazole (Bre) is a new multi-target antipsychotic drug (APD) approved by the US FDA in 2015, and shows good therapeutic potential. But it lacks assessments on the metabolic side effects, which obstructs the treatment of schizophrenia. Glucagon-like peptide 1 (GLP1), an incretin associated with insulin action and metabolism, is involved in the metabolic syndrome (MS) caused by most APDs. In this study, we examined the adverse effects of Bre on glycolipid metabolism in rats and determined whether GLP1 was involved in Bre-caused MS. In the first part of experiments, rats were orally administered Bre (0.5 mg· kg-1· d-1) for 28 days with aripiprazole (1.0 mg· kg-1· d-1) or olanzapine (1.0 mg· kg-1· d-1) as the controls. Compared to vehicle, Bre administration significantly increased the weight gain, serum lipid (TG, TC, LDL, FFA), and blood glucose levels accompanied by the hormonal (insulin, glucagon, GLP1) imbalance, and the impaired glucose tolerance and insulin sensitivity. Moreover, we demonstrated that Bre administration significantly decreased the protein and mRNA levels of GLP1 in pancreas and small intestine by suppressing CaMKIIα, AMPK, and ß-catenin; Bre administration also caused islet dysfunction with decreased GLP1R, PI3K, IRß expression in pancreas, and the interference of IRS1, PI3K, p-AKT, and GLUT4 expression in the liver and skeletal muscle that represented the insulin resistance. In the second part of experiments, rats were orally administered Bre (0.5 mg· kg-1· d-1) for 42 days. We showed that co-administration with the GLP1 receptor (GLP1R) agonist liraglutide (0.125 mg· kg-1· d-1, ip) could ameliorate Bre-caused metabolic abnormalities. Our results demonstrate that GLP1/GLP1R signaling is involved in Bre-induced glycolipid metabolic disorders and co-treatment with liraglutide is an effective intervention against those abnormal metabolisms.

Characterization and Benzo[a]pyrene Content Analysis of Camellia Seed Oil Extracted by a Novel Subcritical Fluid Extraction.

A novel continuous subcritical n-butane extraction technique for Camellia seed oil was explored. The fatty acid composition, physicochemical properties, and benzo[a]pyrene content of Camellia seed oil extracted using this subcritical technique were analyzed. Orthogonal experiment design (L9(34)) was adopted to optimize extraction conditions. At a temperature of 45 °C, a pressure of 0.5 MPa, a time of 50 min and a bulk density of 0.7 kg/L, an extraction yield of 99.12 ± 0.20 % was obtained. The major components of Camellia seed oil are oleic acid (73.12 ± 0.40 %), palmitic acid (10.38 ± 0.05 %), and linoleic acid (9.15 ± 0.03 %). Unsaturated fatty acids represent 83.78 ± 0.03 % of the total fatty acids present. Eight physicochemical indexes were assayed, namely, iodine value (83.00 ± 0.21 g I/100 g), saponification value (154.81 ± 2.00 mg KOH/g), freezing-point (-8.00 ± 0.10 °C), unsaponifiable matter (5.00 ± 0.40 g/kg), smoke point (215.00 ± 1.00 °C), acid value (1.24 ± 0.03 mg KOH/g), refrigeration test (transparent, at 0 °C for 5.5 h), and refractive index (1.46 ± 0.06, at 25 °C). Benzo[a]pyrene was not detected in Camellia seed oil extracted by continuous subcritical n-butane extraction. In comparison, the benzo[a]pyrene levels of crude Camellia seed oil extracted by hot press extraction and refined Camellia seed oil were measured at 26.55 ± 0.70 and 5.69 ± 0.04 µg/kg respectively.

[Characterization of microstructure of ibuprofen-hydroxypropyl-beta-cyclodextrin and ibuprofen-beta-cyclodextrin by atomic force microscope].

The microstructures of ibuprofen-hydroxypropyl-bets-cyclodextrin (IBU-HP-beta-CyD) and ibuprofen-beta-cyclodextrin (IBU-beta-CyD) were observed by atomic force microscope (AFM). The high resolving capability of AFM has the tungsten filament probe with the spring constant of 0.06 N x m(-1). Samples were observed in a small scale scanning area of 10.5 nm x 10.5 nm and 800 x 800 pixels. The original scanning images were gained by tapping mode at room temperature. Their three-dimensional reconstruction of microstructure was performed by G3DR software. The outer diameters of HP-beta-CyD and beta-CyD are 1.53 nm. The benzene diameter of IBU is 0.62 nm, fitting to the inner diameters of HP-beta-CyD and beta-CyD. The benzene and hydrophobic chain of IBU enter into the hole of cyclodextrin at 1:1 ratio. The results were evidenced by IR, X-ray diffraction and the phase solubility.