Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway.

Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata, is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.

Metabolomics analysis of the antidepressant prescription Danzhi Xiaoyao Powder in a rat model of Chronic Unpredictable Mild Stress (CUMS).

ETHNOPHARMACOLOGICAL RELEVANCE: Danzhi Xiaoyao Powder (DZXY) is a classical prescription, that has been extensively used in traditional Chinese medicine (TMC) to treat depression for many years. However, the mechanism of DZXY is still unclear. AIM OF THE STUDY: The aim was to investigate the mechanism of the antidepressant effect of DZXY on a rat model of chronic unpredictable mild stress (CUMS). MATERIALS AND METHODS: Forty male SD (Sprague-Dawley) rats with similar open field test (OFT) results were randomLy divided into a control group (n = 10) and an experimental group (n = 30). A depression model was established in the experimental group using the CUMS method. After the CUMS model was established successfully, the rats were randomLy divided into a depression model group and a DZXY group. The DZXY group was fed DZXY, while the depression model group and control group were given an equal amount of 0.5% sodium carboxymethyl cellulose suspension. Intragastric administration was performed once daily for 14 consecutive days. Animal weight, the sugar preference test, the open field test and the forced swimming test were used to evaluate the modeling effect and the antidepressant effect of DZXY. After the experiment, the plasma of rats was collected and the changes in plasma metabolites were analyzed by UPLC/Q-TOF-MS. The UPLC/Q-TOF-MS spectra data were evaluated by pattern recognition analysis to determine the changes in endogenous metabolites in the rat plasma samples. RESULTS: The results of the behavioral investigation showed that the rat model of depression was successfully replicated and that DZXY had an antidepressant effect. Using the UPLC-MS/MS metabolomics platform, partial least squares (PLS) and orthogonal partial least squares (OPLS), metabolic profile models (R2 and Q2 ≥ 0.5) of rat plasma were successfully constructed. The model could distinguish among the control group, the depression model group and the DZXY group. Finally, 38 differential metabolites were identified in the plasma. According to KEGG (http://www.kegg.jp) pathway analysis, amino acid metabolism, lipid metabolism, purine metabolism, the prolactin signaling pathway and bile secretion were enriched and represented the main metabolic pathways influenced in the plasma. CONCLUSIONS: This study successfully established a CUMS depression model. A total of 38 differential metabolites associated with depression were identified in the plasma of rats, 24 of which were modulated by DZXY. These results suggest that DZXY can improve excitability and play an antidepressant role by regulating phenylalanine metabolism, arachidonic acid metabolism, porphyrin metabolism, D-arginine and D-ornithine metabolism, steroid hormone biosynthesis, unsaturated fatty acid biosynthesis and steroid biosynthesis.

Simultaneous Determination of Parecoxib and Its Metabolite Valdecoxib Concentrations in Beagle Plasma by UPLC-MS/MS and Application for Pharmacokinetics Study.

A method for the simultaneous determination of parecoxib and its metabolite valdecoxib in beagle plasma by UPLC-MS/MS was developed and validated. After the plasma was extracted by acetonitrile precipitation, the analytes were separated on an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm) using acetonitrile-formic acid as the mobile phase in gradient mode. The analytes were monitored by multiple reaction monitoring (MRM) in electrospray negative ion mode. The mass transfer pairs were m/z 368.97→119.01 for parecoxib, m/z 312.89→118.02 for valdecoxib, and m/z 379.98→316.02 for celecoxib (internal standard, IS). The correlation coefficients of parecoxib and valdecoxib ranged from 5 to 4000 ng/mL were greater than 0.9998. The recovery of parecoxib and valdecoxib was greater than 82.54%. The inter- and intra-day precision RSD values were 1.36~3.65% and 2.28~5.91%, respectively. The accuracy of RE values were -1.38%~1.96%. Finally, the matrix effect (ME) and stability were also within acceptable criteria. This method had been successfully applied to the pharmacokinetics of parecoxib and valdecoxib in beagle plasma after injection of parecoxib (1.33 mg/kg, intramuscular injection).

[Effects of urban wetlands with different shapes on the temperature and humidity of ambient environment.] / 不同形状城市湿地对周边环境温湿度的影响.

To quantify the effects of urban wetlands on temperature and humidity of ambient environment, five urban wetlands with different shapes and surroundings were selected in Daqing City, and the air temperature and relative humidity were investigated in spring, summer and autumn using small-scale quantitative measurement method. The results indicated that the urban wetlands with different shapes all could decrease the temperature and increase the humidity, with the effect being strongest in summer, followed by in spring, and the smallest effect in autumn. The shape of the urban wetland had significant effect on temperature and humidity, which decreased in the order of irregular-shaped wetland > regular-shaped wetland (subcircular-shaped wetland, subcuboid-shaped wetland) > long-shaped wetland. The diurnal variation of temperature and humidity was influenced by the ambient temperature, namely the effect of wetlands was weak in morning and evening, but strong at noon. The maximum effect occurred at12:00-14:00 in spring and autumn, and at 14:00-16:00 in summer.

[Effects of urban river width on the temperature and humidity of nearby green belts in summer].

As an important part of urban ecosystem, urban river plays a vital role in improving urban ecological environment. By the methods of small scale quantitative measurement, this paper analyzed the effects of seven urban rivers with different widths along the Third to Fifth Ring in Beijing on the air temperature and relative humidity of nearby green belts. The results showed that urban river width was the main factor affecting the temperature and humidity of nearby green belts. When the river had a width of 8 m, it had no effects in decreasing temperature but definite effects in increasing humidity; when the river width was 14-33 m, obvious effects were observed in decreasing temperature and increasing humidity; when the river had a width larger than 40 m, the effects in decreasing temperature and increasing humidity were significant and tended to be stable. There existed significant differences in the temperature and humidity between the green belts near the seven rivers and the corresponding controls. The critical width of urban river for the obvious effects in decreasing temperature and increasing humidity was 44 m. The regression equation of the temperature (x) and humidity (y) for the seven green belts nearby the urban rivers in summer was y = 173.191-3.247x, with the relative humidity increased by 1.0% when the air temperature decreased by about 0.3 degrees C.

[Relationships between urban green belt structure and temperature-humidity effect].

Taking four green belts with different internal constitutions and five green belts with different canopy densities along the west fourth ring road of Beijing as test objects, and by using small-scale quantitative measurement method, this paper studied the relationships between different structure urban green belts (width 42 m) and temperature-humidity effect in Beijing. Comparing with the control, lawn had no obvious effect on the decrease of air temperature and the increase of relative humidity, while shrub-herbage, tree-shrub-herbage, and tree-herbage had significant effect. When the canopy density was 10%-31%, green belts had definite effect on the decrease of air temperature and the increase of relative humidity; when the canopy density reached 44%, the effect became significant; and when the canopy density exceeded 67%, the effect was significant and stable.