Rhubarb Monomers Protect Intestinal Mucosal Barrier in Sepsis via Junction Proteins

Abstract

Background:Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins.Methods:Healthy male Sprague-Dawley rats (weighing 230–250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0.5 mg/kg) immediately after CLP surgery; and rhubarb monomer (100 mg/kg in normal saline)-treated groups (Group D: rhein; Group E: emodin; Group F: 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid; Group G: 1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose; and Group H: daucosterol linoleate). Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannitol concentrations were measured, and zonula occludens (ZO)-1, occludin and claudin-5 transcription (polymerase chain reaction), translation (by Western blot analysis), and expression (by immunohistochemistry) were also measured.Results:Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A (0.17 ± 0.41), the pathological scores in Groups B (2.83 ± 0.41, P < 0.001), C (1.83 ± 0.41, P < 0.001), D (2.00 ± 0.63, P < 0.001), E (1.83 ± 0.41, P < 0.001), F (1.83 ± 0.75, P < 0.001), G (2.17 ± 0.41, P < 0.001), and H (1.83 ± 0.41, P < 0.001) were significantly increased. Lactulose/mannitol (L/M) ratio in Group B (0.046 ± 0.003) was significantly higher than in Group A (0.013 ± 0.001, P < 0.001) while L/M ratios in Groups C (0.028 ± 0.002, P < 0.001), D (0.029 ± 0.003, P < 0.001), E (0.026 ± 0.003, P < 0.001), F (0.027 ± 0.003, P < 0.001), G (0.030 ± 0.005, P < 0.001), and H (0.026 ± 0.002, P < 0.001) were significantly lower than that in Group B. ZO-1, occludin and claudin-5 transcription, translation, and expression in Group B were significantly lower than that in Group A (P < 0.001), but they were significantly higher in Groups C, D, E, F, G, and H than those in Group B (P < 0.05).Conclusion:Rhubarb monomer treatment ameliorated mucosal damage in sepsis via enhanced transcription, translation, and expression of junction proteins.

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

“…This model accurately represents the progression and properties of human sepsis. The model has a haemodynamic and metabolic phase similar to abdominal infections, accompanied by the presence of different stages of inflammation, as well as a prolonged and reduced cytokine release (11).…”

“…Tight junctions (TJs) between epithelial cells are disrupted and paracellular gaps are widened (10), leading to impaired intestinal mucosal integrity. Furthermore, damage to the intestinal mucosa exacerbates bacterial translocation, leading to virulence factors that further activate the host immune inflammatory defence mechanisms, eventually resulting in multiple organ failure and life-threatening clinical symptoms (11). Destruction of the intestinal barrier integrity may be an important pathway which leads to the multiple organ dysfunction caused by sepsis (12).…”

“…Ning et al (18) showed that emodin can alleviate intestinal mucosal damage in experimental severe acute pancreatitis by inhibiting inflammatory cytokines, including interleukin (IL)-1β and IL-18. Wang et al (11), found that rhubarb monomers could promote the expression of the TJ proteins claudin-5, zonula occludens (ZO)-1 and occludin and that this protected the intestinal mucosal barrier of rats with sepsis induced by cecal ligation and puncture (CLP). However, there is still no evidence showing the mechanism of action by which emodin protects the intestinal epithelial barrier integrity during sepsis.…”

Adjuvant rhubarb alleviates organs dysfunction and inhibits inflammation in heat stroke

“…Emodin was also reported to inhibit oxidative stress and inflammatory response to lung injury via the p38 mitogen-activated protein kinase pathway during sepsis and significantly alleviate sodium taurocholate-induced pancreatic acinar cell injury by decreasing the release of inflammatory factors (tumor necrosis factor-α, IL-1β and IL-6) (23,24). The active components of rhubarb may have an important role in heat stroke by modulating molecular signaling pathways including junction proteins (25) and JAK1/STAT3 (10). Although experimental studies claim that rhubarb and rhein have a protective effect on rats with brain damage (26,27), such a phenomenon occurring in the brains of the patients of the present study was not observable to judge the improvement of the state of mind of patients linked to the application of rhubarb.…”

Fecal microbiota transplantation reconstructs the gut microbiota of septic mice and protects the intestinal mucosal barrier

“…The cell gap was significantly wider, and both cells and organelles were swollen. Mice had not only intestinal barrier dysfunction but also cellular dysfunction.The main functions of occludin are regulation and sealing of TJs41,42 .…”