Procyanidin A1 alleviates DSS-induced ulcerative colitis via regulating AMPK/mTOR/p70S6K-mediated autophagy
J. physiol. biochem
; 78(1): 213-227, feb. 2022.
Artigo
em Inglês
| IBECS
| ID: ibc-215884
Biblioteca responsável:
ES1.1
Localização: ES15.1 - BNCS
ABSTRACT
Ulcerative colitis (UC) is a recurrent chronic inflammatory disease. The symptom of UC is mainly diarrhea including bloody stools. Increasing evidence has suggested that procyanidin A1 (PCA1) exerts an anti-inflammatory effect in several diseases. However, the role of PCA1 in UC is still a mystery. In our study, we explored the effect of PCA1 in dextran sulfate sodium (DSS)induced UC mice and lipopolysaccharide (LPS)-stimulated HT-29 and IEC-6 cells. Then, cell proliferation, apoptosis, the production of proinflammatory cytokines, and autophagy-related markers were determined. Furthermore, the AMPK/mTOR/p70S6K signaling pathway was assayed by Western blot assay. In in vivo study, we found that PCA1 administration alleviated DSS-induced UC, as evidenced by reducing weight loss, clinical scores, colon weight/length ratio, histological damage, proinflammatory cytokines, and apoptosis. Moreover, we showed that the expression of Beclin-1 and LC3II/I ratio was increased, whereas the level of p62 was decreased after PCA1 treatment in vivo. Meanwhile, the reduced AMP/ATP ratio, enhanced expression of p-AMPK, and decreased p-p70S6K and p-mTOR levels indicate the activation of AMPK/mTOR/p70S6K signaling pathway. In in vitro study, PCA1 promoted cell proliferation and inhibited cell apoptosis in LPS-stimulated HT-29 and IEC-6 cells. Pro-inflammatory cytokines and autophagy-related factors exhibited the same trend as in in vivo results. Mechanically, PCA1 activated the AMPK/mTOR/p70S6K signaling pathway. The treatment with an AMPK inhibitor compound C significantly reversed the anti-inflammatory effect of PCA1 in LPS-stimulated cells. Taken together, these data indicated that PCA1 alleviated UC through induction of AMPK/mTOR/p70S6K-mediated autophagy. (AU)
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Coleções:
Bases de dados nacionais
/
Espanha
Base de dados:
IBECS
Assunto principal:
Colite Ulcerativa
/
Proteínas Quinases S6 Ribossômicas 70-kDa
Limite:
Humanos
Idioma:
Inglês
Revista:
J. physiol. biochem
Ano de publicação:
2022
Tipo de documento:
Artigo
Instituição/País de afiliação:
Hebei Normal University of Science and Technology/People's Republic of China
/
Shangluo University/People's Republic of China
/
Technological Innovation Center for Fur Animal Breeding of Hebei Province/People's Republic of China