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.
Sepsis is a common critical illness in ICU and always a great difficulty in clinical treatment. GPR43 (G protein-coupled receptor 43) participates in regulating appetite and gastrointestinal peptide secretion to modulate fat decomposition and formation. However, the biological contribution of GPR43 on inflammation of sepsis has not been previously investigated. We investigated the mechanisms of GPR43 gene, which plays a possible role in distinguishing sepsis and contributes to the pathogenesis of sepsis-induced inflammatory reaction. Furthermore, we performed studies with mice induced to sepsis by Cecal Ligation and Puncture (CLP), Knockout GPR43 (GPR43-/-) mice, and Wild Type (WT) mice induced with CLP. In addition, lung tissues and cell samples were analyzed by histology, Quantitative Polymerase Chain Reaction (Q-PCR), Enzyme-linked Immunosorbent (ELISA) Assay, and western blot. GPR43 agonist could significantly reduce inflammation reactions and trigger lung injury in mice with sepsis. As for GPR43-/- mice, the risks of sepsis-induced inflammatory reactions and corresponding lung injury were promoted. On the one hand, the up-regulation of GPR43 gene reduced ROS mitochondrial damage to inhibit inflammatory reactions via the inactivation of NLRP3 Inflammasome by PPARγ/ Nox1/EBP50/ p47phox signal channel. On the other hand, the down-regulation of GPR43 promoted inflammatory reactions
in vitro
model through the acceleration of ROS-dependently mitochondrial damage by PPARγ/ Nox1/EBP50/ p47phox/ NLRP3 signal channel. These findings indicate that the inhibition of GPR43 as a possible important factor of sepsis may shed lights on the mechanism of sepsis-induced inflammation reaction.
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.
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