Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence in many countries. The purpose of this study is to explore the function of Schisandrin B and its underlying molecular mechanisms in colitis. In this study, mice with colitis were induced by giving 2.0% dextran sulfate sodium (DSS, MP) in the drinking water for seven days. Furthermore, TCMSP server and GEO DataSets were used to analyze the mechanism of Schisandrin B in colitis. It was found that Schisandrin B presented colitis in mice model. At the same time, Schisandrin B not only reduced inflammation in vivo and vitro model of colitis, but also suppressed the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome in vivo and vitro model of colitis. In addition, Schisandrin B induced AMP-activated protein kinase (AMPK) / Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in model of colitis, and regulated AMPK protein at 316 sites. The inhibition of AMPK reduced the anti-inflammation effects of Schisandrin B on NLRP3 inflammasome. Apart from that, Schisandrin B decreased reactive oxygen species (ROS)-induced mitochondrial damage and reduced epithelial cells damage of colitis through regulating pyroptosis. Collectively, our novel findings for first time showed that, Schisandrin B suppressed NLRP3 inflammasome activation-mediated interleukin-1beta (IL-1β) level and pyroptosis in intestinal epithelial cells of colitis model through the activation of AMPK/Nrf2 dependent signaling-ROS-induced mitochondrial damage, which may be a significant therapeutic approach in the treatment of acute colitis.

Oat containing rich β-glucan, polyphenols, flavonoids, saponins, alkaloids, and other substances shows good biological activities. Therefore, the present study aimed to uncover the possible mechanism and therapeutic effect of Avenanthramide C in lessening inflammatory responses in pediatric pneumonia. Pediatric pneumonia was induced by liposaccharide (LPS) for vivo model and vitro model. Macrophage was performed to determine the mechanism and effects of Avenanthramide C in pediatric pneumonia. NLRP3 activity participated in the effects of Avenanthramide C in pediatric pneumonia. Avenanthramide C induced p-PI3K and p-Akt expressions and reduced ubiquitination of PI3K expression in pediatric pneumonia. On the other hand, Avenanthramide C integrated serine at 821 sites of the PI3K protein function. Avenanthramide C reduced ROS (reactive oxygen species)-induced mitochondrial damage by PI3K/AKT function in a model of pediatric pneumonia. Avenanthramide C protects pyroptosis in a model of pediatric pneumonia by PI3K/AKT/Nrf2/ROS signaling. Taken together, our results demonstrated that Avenanthramide C protects pyroptosis through dependent ROS-induced mitochondrial damage by PI3K ubiquitination and phosphorylation in a model of pediatric pneumonia, suggesting its potential use for the treatment of pediatric pneumonia and other inflammatory diseases.

Background: Propylthiouracil (PTU) treats hyperthyroidism and thyroid crisis in all age groups. A variety of serious adverse effects can occur during clinical use and require attention to its pharmacokinetic and pharmacodynamic characteristics in various populations.Objective: To provide information for individualized dosing and clinical evaluation of PTU in the clinical setting by developing a physiologically based pharmacokinetic (PBPK) model, predicting ADME characteristics, and extrapolating to elderly and pediatric populations.Methods: Relevant databases and literature were retrieved to collect PTU’s pharmacochemical properties and ADME parameters, etc. A PBPK model for adults was developed using PK-Sim® software to predict tissue distribution and extrapolated to elderly and pediatric populations. The mean fold error (MFE) method was used to compare the differences between predicted and observed values to assess the accuracy of the PBPK model. The model was validated using PTU pharmacokinetic data in healthy adult populations.Result: The MFE ratios of predicted to observed values of AUC0-t, Cmax, and Tmax were mainly within 0.5 and 2. PTU concentrations in various tissues are lower than venous plasma concentrations. Compared to healthy adults, the pediatric population requires quantitative adjustment to the appropriate dose to achieve the same plasma exposure levels, while the elderly do not require dose adjustments.Conclusion: The PBPK model of PTU was successfully developed, externally validated, and applied to tissue distribution prediction and special population extrapolation, which provides a reference for clinical individualized drug administration and evaluation.