Abstract

Crohn’s disease is a chronic inflammatory bowel disease and the NLRP3 inflammasome plays an important role in Crohn’s disease. Previous studies have shown that Herb-partitioned moxibustion treating (at Qihai (CV 6) and Tianshu (ST 25)) prevented the excessive activation of the NLRP3 inflammasome and repaired damaged colonic mucosa in Crohn’s disease. However, the mechanism by which Herb-partitioned moxibustion (at CV 6 and ST 25) regulates NLRP3 remains unclear. In this study, we treated Crohn’s disease rats with herb-partitioned moxibustion (at CV 6 and ST 25) to investigate the mechanism by which Herb-partitioned moxibustion regulates the colonic NLRP3 inflammasome by observing colon length, the colon macroscopic damage indexes, and the expression of ATP, P2X7R, Pannexin-1, NF-κBp65, NLRP3, ASC, caspase-1, IL-1β and IL-18 in the colon in Crohn’s disease. Here, this study shows that herb-partitioned moxibustion (at CV 6 and ST 25) can reduce colon macroscopic damage indexes and colon histopathological scores, alleviate colon shortening and block the abnormal activation of the NLRP3 inflammasome by inhibiting the ATP content and the expression of P2X7R, Pannexin-1 and NF-κBp65, thereby reducing the release of the downstream inflammatory cytokine IL-1β and ultimately suppressing colonic inflammation in Crohn’s disease rats. This study for the first time identifies the mechanism by which herb-partitioned moxibustion (at CV 6 and ST 25) may inhibit the abnormal activation of the NLRP3 inflammasome by inhibiting the P2X7R-Pannexin-1 signaling pathway in Crohn’s disease rats.

Highlights

  • Crohn’s disease (CD) is a chronic inflammatory bowel disease that first manifests as typical clinical symptoms of diarrhea, abdominal pain, perianal fistulas, abdominal mass, and bowel obstruction [1]

  • The combination of extracellular ATP and P2X7 receptor (P2X7R) allows the passage of cations, including Ca2+, Na+, and K+, across the plasma membrane [23, 24], and recruits Pannexin-1 to mediate the opening of hemichannels and promote the release of intracellular ATP [25]

  • The combination of extracellular ATP and P2X7R allows the passage of cations, including Ca2+, Na+, and K+, across the plasma membrane [23, 24], recruits Pannexin-1 to mediate the opening of hemichannels [43], and induces the activation of nuclear factor-κB (NF-κB), which causes NLRP3 transcription [27, 28, 44]

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Summary

Introduction

Crohn’s disease (CD) is a chronic inflammatory bowel disease that first manifests as typical clinical symptoms of diarrhea, abdominal pain, perianal fistulas, abdominal mass, and bowel obstruction [1]. Some patients choose surgery [3], but surgical intervention for CD requires further study because it is associated with a high recurrence rate [4, 5]. Medications used to maintain remission include 5-aminosalicylic acid products, corticosteroids and immunomodulators. All of these medications have adverse effects [6, 3]. Clinical studies have demonstrated that herb-partitioned moxibustion (HPM) is effective in treating CD [12, 13]. HPM exerts its therapeutic effects by regulating intestinal epithelial barrier function [14,15,16], autophagy and immune function in colon tissues [17] and it is known for to affect multiple targets, have multiple effects and exhibit high safety

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