QingBai decoction regulates intestinal permeability of dextran sulphate sodium-induced colitis through the modulation of notch and NF-κB signalling

Cell Prolif. 2019 Mar;52(2):e12547. doi: 10.1111/cpr.12547. Epub 2019 Jan 18.

Abstract

Objective: Chinese Herb QingBai decoction (QBD) has been approved affective in the treatment of IBD patients in clinic. However, the underlying mechanism remains unknown. We aim to investigate the effect of QBD on the mouse model of ulcerative colitis and its possible mechanism.

Methods: C57/bL mice were given 5% DSS to induce colitis and were divided as QBD and mesalazine group. Weight, faeces and mental status were recorded each day and the histopathological changes (goblet cells etc) of the colon were observed after sacrificed. Fluorescein isothiocyanate-dextran 4000 was measured to reflect the intestinal mucosal permeability. In addition, cell junction-related proteins and possible signal pathways were investigated.

Results: QingBai decoction could significantly alleviate the inflammation and the protection effect of colitis is comparable as those in mesalazine enema group. It was found that the permeability reduced significantly with QBD treatment vs the control group, while no significant difference between the mesalazine and QBD groups. QBD treatment could upregulate the expression of tight junction complex(ZO-1, claudin-1 and occludin)and muc-2 expression. It significantly reduced the production and secretion of serials proinflammatory cytokines (IL-1β, IL-6, Kc and TNF-α) compared with the control group. Meanwhile, NF-κB and Notch pathways were regulated.

Conclusion: QingBai decoction can effectively alleviate intestinal inflammation and mucosal barrier function in colitis mice, and the mechanism may be related to the inhibition of inflammatory cascade as well as enhanced mucus layer barrier and mechanical barrier function by NF-κB and Notch signalling.

Keywords: MMP-9; Mucin-2; Notch; QingBai decoction; intestinal permeability; ulcerative colitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / pathology
  • Cytokines / analysis
  • Cytokines / immunology
  • Dextran Sulfate
  • Disease Models, Animal
  • Drugs, Chinese Herbal / therapeutic use*
  • Intestinal Absorption / drug effects*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Intestines / drug effects*
  • Intestines / immunology
  • Intestines / pathology
  • Mice, Inbred C57BL
  • NF-kappa B / analysis
  • NF-kappa B / immunology*
  • Permeability / drug effects
  • Receptors, Notch / analysis
  • Receptors, Notch / immunology
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Drugs, Chinese Herbal
  • NF-kappa B
  • Receptors, Notch
  • Dextran Sulfate