1. Academic Validation
  2. Paeoniflorin promotes intestinal stem cell-mediated epithelial regeneration and repair via PI3K-AKT-mTOR signalling in ulcerative colitis

Paeoniflorin promotes intestinal stem cell-mediated epithelial regeneration and repair via PI3K-AKT-mTOR signalling in ulcerative colitis

  • Int Immunopharmacol. 2023 May 7;119:110247. doi: 10.1016/j.intimp.2023.110247.
Yujing Ma 1 Xiaomeng Lang 2 Qian Yang 2 Yan Han 2 Xin Kang 2 Run Long 2 Jingxia Du 3 Mengmeng Zhao 4 Longhui Liu 4 Peitong Li 4 Jianping Liu 5
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Hebei University of Chinese Medicine, China; Hebei University of Chinese Medicine, China.
  • 2 The First Affiliated Hospital of Hebei University of Chinese Medicine, China.
  • 3 Xingtai Medical College, China.
  • 4 Hebei University of Chinese Medicine, China.
  • 5 The First Affiliated Hospital of Hebei University of Chinese Medicine, China. Electronic address: 1535392045@hebcm.edu.cn.
Abstract

Ulcerative colitis (UC) is a chronic and immune-mediated inflammatory disorder characterized by abdominal pain, diarrhoea, and haematochezia. The goal of clinical therapy for UC is mucosal healing, accomplished by regenerating and repairing the intestinal epithelium. Paeoniflorin (PF) is a natural ingredient extracted from Paeonia lactiflora that has significant anti-inflammatory and immunoregulatory efficacy. In this study, we investigated how PF could regulate the renewal and differentiation of intestinal stem cells (ISCs) to improve the regeneration and repair of the intestinal epithelium in UC. Our experimental results showed that PF significantly alleviated colitis induced by dextran sulfate sodium (DSS) and ameliorated intestinal mucosal injury by regulating the renewal and differentiation of ISCs. The mechanism by which PF regulates ISCs was confirmed to be through PI3K-AKT-mTOR signalling. In vitro, we found that PF not only improved the growth of TNF-α-induced colon organoids but also increased the expression of genes and proteins related to the differentiation and regeneration of ISCs. Furthermore, PF promoted the repair ability of lipopolysaccharide (LPS)-induced IEC-6 cells. The mechanism by which PF regulates ISCs was further confirmed and was consistent with the in vivo results. Overall, these findings demonstrate that PF accelerates epithelial regeneration and repair by promoting the renewal and differentiation of ISCs, suggesting that PF treatment may be beneficial to mucosal healing in UC patients.

Keywords

Colon organoids; Intestinal stem cells (ISCs); PI3K-AKT-mTOR; Paeoniflorin; Ulcerative colitis.

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