Mogrol, an aglycone of mogrosides, attenuates ulcerative colitis by promoting AMPK activation

Phytomedicine. 2021 Jan:81:153427. doi: 10.1016/j.phymed.2020.153427. Epub 2020 Nov 30.

Abstract

Background: Ulcerative colitis (UC) is a non-specific chronic inflammatory disease. The incidence of UC in China has been increasing in recent years. Mogrol is an aglycone of mogrosides. Studies have shown that mogrosides have anti-oxygenation, anti-inflammatory, and laxative effects as well as other biological activities.

Purpose: To investigate the beneficial effects of mogrol on UC and identify its underlying mechanisms.

Study design: We used the dextran sodium sulphate (DSS)-induced UC model in mice, TNF-α-damaged NCM460 colonic epithelial cells, macrophage cells THP-M stimulated with lipopolysaccharide (LPS) / adenosine triphosphate (ATP) and compound C (an AMPK inhibitor) to confirm the key role of AMPK (AMP-activated protein kinase) activation.

Methods: Histological evaluation, immunohistochemical staining, Western blot analysis, immunofluorescence assay and quantitative real time-PCR were used in the study.

Results: Oral administration of mogrol (5 mg/kg/daily) in vivo significantly attenuated pathological colonic damage, inhibited inflammatory infiltration and improved the abnormal expression of NLRP3 inflammasome in colonic mucosa via the AMPK and NF-κB signaling pathways. In vitro, mogrol protected against intestinal epithelial barrier dysfunction by activating AMPK in TNF-α-treated NCM460 cells and inhibited the production of inflammatory mediator in LPS-stimulated THP-M cells. Furthermore, mogrol's effects were reversed by compound C intervention in DSS-induced UC model.

Conclusion: Mogrol exerts protective effects in experimental UC and inhibits production of inflammatory mediators through activation of AMPK-mediated signaling pathways.

Keywords: AMPK; Mogrol; NLRP3 inflammasome; SIRT1; Ulcerative colitis.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / metabolism
  • Dextran Sulfate / toxicity
  • Enzyme Activation
  • Female
  • Humans
  • Inflammasomes / drug effects
  • Inflammasomes / metabolism
  • Inflammation Mediators / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • THP-1 Cells

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Inflammasomes
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Dextran Sulfate
  • AMP-Activated Protein Kinases