Your browser doesn't support javascript.
loading
Magnolin inhibits intestinal epithelial cell apoptosis alleviating Crohn's disease-like colitis by suppressing the PI3K/AKT signalling pathway.
Zhang, Min; Song, Xue; Liu, Shengbao; Zhang, Nuo; Yang, Ming; Gao, Pengcheng; Geng, Zhijun; Zuo, Lugen; Zhang, Xiaofeng; Wang, Lian; Wang, Yueyue; Li, Jing; Hu, Jianguo.
Afiliación
  • Zhang M; Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Department of Laboratory Medicine, Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China.
  • Song X; Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China.
  • Liu S; Department of Pathology, First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
  • Zhang N; Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Department of Laboratory Medicine, Bengbu Medical University, Bengbu, China.
  • Yang M; Department of Laboratory Medicine, Bengbu Medical University, Bengbu, China.
  • Gao P; Department of Laboratory Medicine, Bengbu Medical University, Bengbu, China.
  • Geng Z; Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China.
  • Zuo L; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China; Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
  • Zhang X; Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China.
  • Wang L; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China; Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
  • Wang Y; Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China.
  • Li J; Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China.
  • Hu J; Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China. Electronic address: jghu9200@bbmc.edu.cn.
Int Immunopharmacol ; 134: 112181, 2024 Jun 15.
Article en En | MEDLINE | ID: mdl-38733829
ABSTRACT
BACKGROUND AND

AIMS:

Previous reports have shown that preventing excessive intestinal epithelial cell (IEC) apoptosis is a crucial approach for protecting the intestinal barrier in patients with Crohn's disease (CD). Magnolin (MGL) has various biological activities, including antiapoptotic activities, but its role in CD has largely not been determined. This study investigated how MGL impacts CD-like colitis and the underlying mechanism involved.

METHODS:

Mice were treated with TNBS to establish a disease model, and these mice were used to assess the therapeutic effects of MGL on CD-like colitis. TNF-α-treated colon organoids were used to evaluate the impact of MGL on intestinal barrier function and IEC apoptosis. Enrichment analysis was performed to examine the potential pathways through which MGL inhibits IEC apoptosis. Finally, rescue experiments showed the mechanism by which MGL suppresses IEC apoptosis.

RESULTS:

The animal experiments demonstrated that MGL treatment alleviated the weight loss, colon shortening, elevated disease activity index (DAI) scores, increased colitis histological scores and upregulated inflammatory factor expression that were observed in model mice. MGL ameliorated intestinal barrier dysfunction and the loss of tight junction (TJ) proteins (ZO-1 and Claudin-1) by inhibiting IEC apoptosis in both TNBS-treated mice and TNF-α-treated colon organoids. MGL inhibited the PI3K/AKT signalling pathway, thus safeguarding the intestinal barrier and alleviating CD-like colitis in vivo and in vitro.

CONCLUSIONS:

MGL improves the intestinal barrier integrity and prevents CD-like colitis by inhibiting IEC apoptosis. The potential mechanism of its anti-apoptotic impact on IECs could be associated with the PI3K/AKT pathway, presenting novel approaches and avenues for the clinical management of CD.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Trinitrobencenosulfónico / Transducción de Señal / Enfermedad de Crohn / Apoptosis / Colitis / Fosfatidilinositol 3-Quinasas / Modelos Animales de Enfermedad / Proteínas Proto-Oncogénicas c-akt / Mucosa Intestinal Límite: Animals / Humans / Male Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Trinitrobencenosulfónico / Transducción de Señal / Enfermedad de Crohn / Apoptosis / Colitis / Fosfatidilinositol 3-Quinasas / Modelos Animales de Enfermedad / Proteínas Proto-Oncogénicas c-akt / Mucosa Intestinal Límite: Animals / Humans / Male Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China
...