2. Academic Validation
  3. Sotetsuflavone ameliorates Crohn's disease-like colitis by inhibiting M1 macrophage-induced intestinal barrier damage via JNK and MAPK signalling

Sotetsuflavone ameliorates Crohn's disease-like colitis by inhibiting M1 macrophage-induced intestinal barrier damage via JNK and MAPK signalling

  • Eur J Pharmacol. 2023 Feb 5:940:175464. doi: 10.1016/j.ejphar.2022.175464.
Sitang Ge 1,  Yating Yang 2,  Lugen Zuo 2,  Xue Song 3,  Hexin Wen 4,  Zhijun Geng 5,  Yifan He 2,  Zilong Xu 2,  Huatao Wu 2,  Mengdi Shen 2,  Yuanyuan Ge 6,  Xuejun Sun 7
Affiliations

Affiliations

  • 1 Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, China; Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
  • 2 Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China; Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China.
  • 3 Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China; Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
  • 4 Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
  • 5 Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
  • 6 Department of Colorectal Surgery, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
  • 7 Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, China. Electronic address: sunxy@mail.xjtu.edu.cn.
PMID: 36566007 DOI: 10.1016/j.ejphar.2022.175464
Abstract

Objectives: Intestinal inflammation and intestinal barrier dysfunction are two important pathological changes in Crohn's disease (CD). Sotetsuflavone (SF) is a natural monomeric herbal compound with anti-inflammatory and cytoprotective effects that is mostly nontoxic. The effect of SF on CD-like spontaneous colitis was investigated in this study.

Methods: IL-10-/- mice were used as a CD model and were administered different doses of SF. Lipopolysaccharide (LPS) plus IFN-γ-induced macrophages (RAW264.7) and a coculture system (RAW264.7 and organoids) were used in vitro. The protective effects of SF against CD-like colitis and macrophage differentiation and the mechanisms were evaluated.

Results: SF treatment markedly improved spontaneous colitis in the CD model, as shown by the following evidence: reductions in the DAI, macroscopic scores (3.63 ± 1.30), colonic tissue inflammatory scores (2 ± 0.76) and proinflammatory factor levels and the attenuation of colon shortening (8 ± 0.93 cm) and weight loss (1.75 ± 1.83 g). Decreased intestinal permeability and intestinal Bacterial translocation rates provided evidence of the protective effect of SF on intestinal barrier function. We also found that SF suppressed M1 macrophage-induced inflammatory responses. In the coculture system of mouse colonic organoids and RAW264.7 cells, SF significantly ameliorated M1 macrophage-induced intestinal epithelial damage. In addition, SF inhibited JNK and MAPK (p38) signalling in both IL-10-/- mice and LPS plus IFN-γ-induced macrophages (RAW264.7).

Conclusions: The protective effects of SF against CD-like colitis may be achieved partially by inhibiting M1 macrophage-induced intestinal barrier damage via JNK and p38 signalling. SF may have therapeutic potential for treating CD, especially considering its safety.

Keywords

Crohn's disease; Intestinal barrier function; MAPK; Macrophages; Sotetsuflavone.

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