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Pure total flavonoids from Citrus ameliorate NSAIDs-induced intestinal mucosal injury via regulation of exosomal LncRNA H19 and protective autophagy.
Chen, Shanshan; He, Ruonan; Li, Ying; Zhang, Shuo.
Afiliación
  • Chen S; The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, 310053, Zhejiang, China.
  • He R; The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China.
  • Li Y; The Second Affiliated Hospital of Zhejiang Chinese Medical University (The Xin Hua Hospital of Zhejiang Province), Hangzhou, 310053, Zhejiang, China.
  • Zhang S; The Second Affiliated Hospital of Zhejiang Chinese Medical University (The Xin Hua Hospital of Zhejiang Province), No. 318 Chaowang Road, Hangzhou, 310005, Zhejiang, China.
Heliyon ; 10(9): e29797, 2024 May 15.
Article en En | MEDLINE | ID: mdl-38707329
ABSTRACT

Introduction:

Non-steroid anti-inflammatory drugs (NSAIDs) are a class of prescription drugs with antipyretic, analgesic, anti-inflammatory, and antiplatelet effects. However, long-term use of NSAIDs will disrupt the intestinal mucosal barrier, causing erosion, ulcers, bleeding, and even perforation. Pure total flavonoids from Citrus (PTFC) is extracted from the dried peel of Citrus, showing a protective effect on intestinal mucosal barrier with unclear mechanisms.

Methods:

In the present study, we used diclofenac (7.5 mg kg-1, i.g.) to induce a rat model of NSAIDs-related intestinal lesions. PTFC (50, 75, 100 mg·kg-1 d-1, i.g.) was administered 9 days before the initial diclofenac administration, followed by co-administration on the last 5 days. Exosomes were identified by western blotting and transmission electron microscopy (TEM), and then co-cultured with IEC-6 cells. The expression of long non-coding RNA (lncRNA) H19, autophagy-related 5 (Atg5), ZO-1, Occludin, and Claudin-1 were detected by quantitative real-time PCR (qRT-PCR). The expression of light chain 3 (LC3)-I, LC3-II, ZO-1, Occludin and Claudin-1 proteins was tested by western blotting. The localization of both exosomes and autophagosomes was examined by immunofluorescent technique.

Results:

The treatment of PTFC attenuated intestinal mucosal mechanical barrier function disturbance in diclofenac-induced NSAIDs rats. IEC-6 cells co-cultured with NSAIDs rats-derived exosomes possessed the lowest levels of protective autophagy, and severe intestinal barrier injuries. Cells co-cultured with the exosomes extracted from rats administrated PTFC exhibited an improvement of autophagy and intestinal mucosal mechanical barrier function. The prevention effect was proportional to the concentration of PTFC administered.

Conclusion:

PTFC ameliorated NSAIDs-induced intestinal mucosal injury by down-regulating exosomal lncRNA H19 and promoting autophagy.
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Heliyon Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Heliyon Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido