Nrf2 (Nuclear Factor Erythroid 2 Related Factor 2) transcription factor not only regulates oxidative stress response, but also represses inflammation by regulating cytokines production and cross-talking with NF-κB signaling pathways. Nrf2 plays an essential role in liver injury induced by oxidative stress and inflammation. Triptriolide (T11) is a minor component of Tripterygium wilfordii Hook F. (TwHF), which can be obtained by hydrolysis reaction of triptolide (T9). The major purpose of this study is to clarify the regulating effects of T11 on oxidative stress and inflammation in vivo and in vitro. LPS-stimulated RAW 264.7 cells were used to verify the regulating effects of T11 on oxidative stress (ROS and Nrf2 signaling pathway) and inflammatory cytokines production (TNF-α, IL-6 and IL-1β). The antioxidant responsive element (ARE) luciferase assay was employed to evaluate Nrf2 activation effect of T11 in HEK-293T cells. Lipopolysaccharides (LPS) induced acute liver injury (ALI) in BALB/c mice were used to study the protective effects (ALT, AST, MDA, SOD, histopathology and neutrophils/macrophages filtration) and the underlying protection mechanisms of ALI amelioration (Nrf2 and NF-κB signaling pathway) of T11. Firstly, the results showed that T11 can not only effectively decrease the productions of inflammatory cytokines (TNF-α, IL-6 and IL-1β), ROS and NO in LPS-stimulated RAW 264.7 cells, but also further significantly increase the activity of Nrf2 in HEK-293T cells. Secondly, the results suggested that T11 could dramatically decrease the oxidative stress responses (SOD and MDA) and inflammation (histopathology, neutrophils/macrophages filtration, TNF-α, IL-6 and IL-1β production) in LPS-induced ALI in BALB/c mice. Finally, the results implied that T11 could dramatically increase Nrf2 protein expression and decrease p-TAK1, p-IκBα and NF-κB protein expression both in vivo and in vitro. In conclusion, our findings indicated that T11 could alleviate LPS induced oxidative stress and inflammation by regulating Nrf2 and NF-κB signaling pathways in vitro and in vivo, which offers a novel insights for the application of TwHF in clinical.

No abstract

SLC25A22, which encodes the mitochondrial glutamate transporter, is overexpressed in colorectal cancer (CRC) and is essential for the proliferation of CRC cells harboring KRAS mutations. However, the role of SLC25A22 on metabolic regulation in KRAS-mutant CRC cells has not been comprehensively characterized.We performed non-targeted metabolomics, targeted metabolomics and isotope kinetic analysis of KRAS-mutant DLD1 cells with or without SLC25A22 knockdown using ultra-high-performance liquid chromatography (UHPLC) coupled to Orbitrap mass spectrometry (MS) or tandem MS (MS/MS).Global metabolomics analysis identified 35 altered metabolites, which were attributed to alanine, aspartate and glutamate metabolism, urea cycle and polyamine metabolism. Targeted metabolomics including 24 metabolites revealed that most tricarboxylic acid (TCA) cycle intermediates, aspartate-derived asparagine, alanine and ornithine-derived polyamines were strongly down-regulated in SLC25A22 knockdown cells. Moreover, targeted kinetic isotope analysis showed that most of the 13C-labeled ornithine-derived polyamines were significantly decreased in SLC25A22 knockdown cells and culture medium. Exogenous addition of polyamines could significantly promote cell proliferation in DLD1 cells, highlighting their potential role as oncogenic metabolites that function downstream of SLC25A22-mediated glutamine metabolism.Collectively, SLC25A22 acts as an essential metabolic regulator during CRC progression as it promotes the synthesis of aspartate-derived amino acids and polyamines in KRAS mutant CRC cells.

The objective of this study was to improve the stability and water-solubility of patchouli alcohol by complexing with β-cyclodextrin (β-CD). The interactions between patchouli alcohol and β-CD were characterized by differential scanning calorimetry (DSC), Fourier transformation-infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), and Scanning electron microscope (SEM), respectively. According to molecular modeling method, the enthalpy formation of host-guest illustrated the predominant configuration and the lowest value ΔbGo was -10.8174±1.9235 kcal/mol, suggesting the complex could reduce the energy of the system. The characterization analysis confirmed the formation of PA-CD inclusion complex, and the results indicated the advantage of the inclusion complex in stability and dissolution rates. These results identified PA-CD inclusion complex an effective way for the storage of PA, and better inclusion method still needed to be studied.