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

Bei Yue, Junyu Ren, Zhilun Yu, Xiaoping Luo, Yijing Ren, Jing Zhang, Sridhar Mani, Zhengtao Wang, Wei Dou

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 (ZO-1, Claudin-1, Occludin and JAM-A) in Caco-2 cells. In conclusion, our work presented evidence that pinocembrin attenuated DSS-induced colitis in mouse, at least in part, via regulating intestinal microbiota, inhibiting the over-activation of TLR4/MD2/NF-κB signaling pathway, and improving the barriers of intestine.

Original languageEnglish (US)
Article numberBSR20200986
JournalBioscience Reports
Volume40
Issue number7
DOIs
StatePublished - Jul 2020

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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