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Potential pharmacological mechanism of Colitis treatment by diosmetin
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  • hailong Li,
  • Yiying Wei,
  • Xiaohe Li,
  • Shanshan Zhang,
  • Ruotong Zhang,
  • jinhe Li,
  • Bowei Ma,
  • Shuaibo Shao,
  • Ziwei Lv,
  • hao Ruan,
  • Honggang Zhou,
  • Cheng Yang
hailong Li
Nankai University
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Yiying Wei
College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University
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Xiaohe Li
Nankai University
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Shanshan Zhang
Nankai University College of Pharmacy
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Ruotong Zhang
Nankai University College of Pharmacy
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jinhe Li
Nankai University
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Bowei Ma
Nankai University College of Pharmacy
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Shuaibo Shao
Nankai University College of Pharmacy
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Ziwei Lv
Nankai University College of Pharmacy
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hao Ruan
Nankai University College of Pharmacy
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Honggang Zhou
Nankai University
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Cheng Yang
Nankai University College of Pharmacy
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Abstract

BACKGROUND AND PURPOSE Diosmetin exhibits a series of therapeutic efficacy but little is known of its effects on colitis. EXPERIMENTAL APPROACH In this study, two mouse models of DSS (the concentration of 3% and 5%)-induced colitis and Caco2 and IEC-6 cells were employed. The 16S amplicon sequencing was used to assess Gut microbiota changes by diosmetin. Various physical signs of mice (body weight, colon length and DAI score), proinflammatory cytokines and antioxidant enzymes were tested. KEY RESULTS The results showed that diosmetin can markedly decrease the disease activity index and microscopic colon tissue damage, increase the expression of tight junction protein (Occludin, Claudin-1 and Zo-1) and reduce the secretion of proinflammatory cytokines. And diosmetin also significantly inhibited colon oxidative damage through adjusting the levels of intracellular ROS, mitochondrial ROS, GSH-Px, SOD, MDA and GSH in vitro and in vivo. Furthermore, it was found that diosmetin can modulate the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were reported to be the crucial bacteria related to inflammatory bowel disease (IBD). Also, diosmetin significantly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, thereby inhibiting oxidative stress and inflammation. CONCLUSIONS AND IMPLICATIONS Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is regulated by diosmetin. It implies that diosmetin may be a novel candidate to alleviate DSS-induced colitis or a lead compound for future optimization and modification.