Pinocembrin alleviates ulcerative colitis in mice via regulating gut microbiota, suppressing TLR4/MD2/NF-κB pathway and promoting intestinal barrier.

Bioscience Reports
Bei YueWei Dou

Abstract

Pinocembrin, a plant-derived flavonoid, has a variety of pharmacological activities, including anti-infection, anti-cancer, anti-inflammation, cardiovascular protection, etc. However, the mechanism of pinocembrin on the anti-colitis efficacy remains elusive and needs further investigation. Here, we reported that pinocembrin eased the severity of dextran sulfate sodium (DSS)-induced colitis in mice by suppressing the abnormal activation of toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signal pathway in vivo. In addition, the gut microbiota was disordered in DSS colitis mice, which was associated with a significant decrease in microbiota diversity and a great shift in bacteria profiles; however, pinocembrin treatment improved the imbalance of gut microbiota and made it similar to that in normal mice. On the other hand, in vitro, pinocembrin down-regulated the TLR4/NF-κB signaling cascades in lipopolysaccharide (LPS)-stimulated macrophages. At the upstream level, pinocembrin competitively inhibited the binding of LPS to myeloid differentiation protein 2 (MD2), thereby blocking the formation of receptor multimer TLR4/MD2·LPS. Furthermore, pinocembrin dose-dependently promoted the expression of tight junction proteins (...Continue Reading

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Methods Mentioned

BETA
PCR
immunoprecipitation assay
nuclear translocation
co-immunoprecipitation

Software Mentioned

GraphPad Prism
Trimmomatic
AutoDock
MOPAC
AutoDockTools
UPARSE
AutoDock Tools
FLASH

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