Protective effect of emodin on intestinal epithelial tight junction barrier integrity in rats with sepsis induced by cecal ligation and puncture

Abstract

Αbstract. The present study investigated the protective effects of emodin on intestinal epithelial tight junction (TJ) barrier integrity in cecal ligation and puncture (CLP)-induced septic rats and its possible mechanisms of action. Healthy male Sprague-Dawley rats were randomly divided into three groups (n=20 per group): Sham group, CLP group and CLP + emodin group. Animals were sacrificed at 12 and 24 h after the model was established. Abdominal aortic blood and specimens of the ileum were harvested for analysis. The histopathological changes in intestinal mucosa and the ultrastructures of intestinal epithelial cells were investigated using light microscopy and transmission electron microscopy. The integrity of the intestinal barrier was assessed by examining plasma diamine oxidase (DAO) levels and the ratio of urine lactulose to mannitol (L/M). The levels of the intestinal TJ proteins claudin-3, zonula occludens (ZO)-1 and occludin were detected using immunohistochemistry, western blotting and reverse transcription-quantitative PCR. The results showed that the pathological damage to intestinal mucosa and the intestinal tissue injury score in the CLP + emodin group were significantly reduced compared to those of the CLP group, and the differences were more obvious at 24 h compared with 12 h. DAO activity and the L/M ratio in the emodin pre-treatment group decreased significantly at 24 h compared with the CLP groups. The protein and mRNA levels of the TJ proteins claudin-3, ZO-1 and occludin in the emodin pre-treatment groups at 12 and 24 h were increased, while occludin mRNA level was found to be decreased compared with the CLP groups. The present study suggested that emodin may significantly reduce the damage to the intestinal epithelial barrier in sepsis, inhibit intestinal barrier permeability and protect intestinal barrier integrity. Emodin may protect intestinal barrier integrity by elevating expression levels of the TJ proteins claudin-3, ZO-1 and occludin in CLP rats.

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“…The MG and CG groups were administered saline and 0.13 mg/kg ciprofloxacin, respectively, by oral gavage; the Em-L, Em-M, and Em-H groups were administered 8.75, 17.5, and 35 mg/kg emodin dissolved in a 0.5% sodium carboxy-methyl-cellulose solution (prepared to contain emodin at 5 g/L), respectively, by oral gavage, once daily. The emodin doses were determined based on the LD50 [ 32 ].…”

HO‐1/CO Maintains Intestinal Barrier Integrity through NF‐κB/MLCK Pathway in Intestinal HO‐1-/- Mice

“…As the major connection between intestinal epithelial cells, the TJ proteins in intestinal mucosa have an important role in maintaining the intestinal mucosa's mechanical barrier integrity and functions [ 1 ]. Decreased expression of TJ proteins leads to the increase of intestinal permeability, thus facilitating the entry of pathogens and toxic substances into the body [ 31 – 33 ]. TNF- α may have a central role in the complex chain reaction of cytokine-mediated intestinal mucosal injury [ 21 , 22 , 34 ].…”

The Health Benefits of Emodin, a Natural Anthraquinone Derived from Rhubarb—A Summary Update

“…It was shown that emodin may significantly reduce the damage to the intestinal epithelial barrier in sepsis, inhibit intestinal barrier permeability and protect intestinal barrier integrity, by elevating expression levels of the TJ proteins: claudin-3, ZO-1 and occludin in cecal ligation and puncture (CLP) rats [110].…”