Procyanidin A1 alleviates DSS-induced ulcerative colitis via regulating AMPK/mTOR/p70S6K-mediated autophagy.

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.

• Authors: Haihua Zhang, Wuying Lang, Xin Liu, Jiangsong Bai, Qinghui Jia, Qiumei Shi
• Journal: Journal of physiology and biochemistry (J Physiol Biochem) Vol. 78 Issue 1 Pg. 213-227 (Feb 2022) ISSN: 1877-8755 [Electronic] Spain
• PMID: 35001346 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s) under exclusive licence to University of Navarra.

Chemical References

• Proanthocyanidins
• procyanidin A1
• Catechin
• Dextran Sulfate
• Ribosomal Protein S6 Kinases, 70-kDa
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (genetics, metabolism)
• Animals
• Autophagy
• Catechin
• Colitis, Ulcerative (chemically induced, drug therapy, metabolism)
• Dextran Sulfate
• Mice
• Proanthocyanidins
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• TOR Serine-Threonine Kinases (genetics, metabolism)