Glycyrol Eases Ulcerative Colitis by Strengthening Cell Membrane Connections

Jim Crocker
12th June, 2024

Glycyrol Eases Ulcerative Colitis by Strengthening Cell Membrane Connections

Image Source: Natural Science News, 2024

Key Findings

  • The study from Shanxi Medical University found that glycyrol (GC), a compound from Licorice, can help alleviate ulcerative colitis (UC)
  • GC promotes the production of glial cell-derived neurotrophic factor (GDNF) in mouse enteric glial cells (EGCs)
  • GDNF activates its receptor RET, enhancing the fusion of the protein ZO-1 with cell membranes, which helps protect the intestinal mucosal barrier
Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon, characterized by periods of remission and flare-ups. The disease can lead to significant morbidity and work disability[2]. Understanding the mechanisms behind UC and finding effective treatments is crucial for improving patient outcomes. A recent study conducted by Shanxi Medical University has uncovered a promising approach to alleviate UC by focusing on the mechanical barrier of the intestinal mucosa[1]. The integrity of the intestinal mucosa is essential for maintaining gut health. Damage to this mechanical barrier is a key factor in the progression of UC. The protein ZO-1 plays a critical role in maintaining this barrier by fusing with the membrane of intestinal epithelial cells. Enteric glial cells (EGCs), which support intestinal homeostasis, have emerged as a new target for regulating intestinal health. This study found that glycyrol (GC), a compound derived from Licorice (Glycyrrhiza uralensis Fisch), can alleviate UC by promoting the production of glial cell-derived neurotrophic factor (GDNF) in mouse EGCs. Previous studies have highlighted the chronic nature of UC and its association with high morbidity and work disability[2]. About 50% of UC patients require hospitalization within five years of diagnosis, and around 10%-15% undergo colectomy within ten years. These findings underscore the need for effective treatments that can modify the disease course and improve patient quality of life[2]. The study by Shanxi Medical University builds on this knowledge by exploring how GC can enhance the intestinal mucosal barrier. GC was shown to promote the production of GDNF in EGCs. GDNF, in turn, activates its receptor RET, leading to the promotion of ZO-1 fusion with cell membranes. This process helps protect the mechanical barrier of the intestinal mucosa, thereby potentially alleviating the symptoms of UC. In addition to mechanical protection, the intestinal barrier also includes functional components like intestinal alkaline phosphatase (IAP) and antibacterial proteins produced by Paneth cells. These elements play vital roles in detoxifying bacterial endotoxins and defending against gut microbes[3]. The study's focus on the mechanical barrier adds another layer of understanding to the complex nature of intestinal barrier function and its role in UC. Long-duration UC patients have been found to exhibit altered gene expressions and pathways compared to those with short-duration UC. These changes are associated with a higher risk of colitis-associated cancer (CAC)[4]. The new findings on GC and GDNF could provide a novel approach to mitigating these risks by strengthening the intestinal barrier and potentially reducing inflammation and disease progression. In summary, the study from Shanxi Medical University offers new insights into the treatment of UC by highlighting the importance of the intestinal mucosal barrier and the role of EGCs. By promoting the production of GDNF and enhancing the fusion of ZO-1 with cell membranes, GC shows promise in protecting the intestinal barrier and alleviating UC symptoms. This research paves the way for developing new therapeutic strategies that could significantly improve the lives of UC patients.

MedicineHealthBiochem

References

Main Study

1) Glycyrol Relieves Ulcerative Colitis by Promoting the Fusion of ZO-1 with the Cell Membrane through the Enteric Glial Cells GDNF/RET Pathway.

Published 11th June, 2024

https://doi.org/10.1021/acs.jafc.4c00239

Related Studies

2) Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review.

https://doi.org/10.1016/j.cgh.2017.06.016

3) Intestinal Barrier Dysfunction, LPS Translocation, and Disease Development.

https://doi.org/10.1210/jendso/bvz039

4) Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways.

https://doi.org/10.1093/ecco-jcc/jjz002


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