Moxifloxacin plus Cordyceps polysaccharide ameliorate intestinal barrier damage due to abdominal infection via anti-inflammation and immune regulation under simulated microgravity

Background

Currently, there is limited research on the impact of abdominal infection on intestinal damage under microgravity conditions. Cordyceps polysaccharide (CPS), the main active ingredient of Cordyceps, has demonstrated various pharmacological effects, including anti-inflammatory, antioxidant, and immunomodulatory properties. Moxifloxacin (MXF) is a fourth-generation quinolone antibiotic that is believed to have a dual regulatory effect on immune system activation and suppression. Our objective was to investigate the effects of MXF plus CPS on the intestinal barrier damage due to abdominal infection under microgravity.

Methods

The hindlimb unloading model in rats was employed to simulate microgravity. The rat model of abdominal infection was established by cecal ligation and puncture (CLP). MXF, CPS and the combination of the two drugs were used to treat CLP-rats in simulated microgravity. We assessed histopathological changes of ileum by hematoxylin and eosin staining. The intestinal ultrastructure was observed under transmission electron microscopy. Additionally, the expression of intestinal barrier proteins RegIII α/γ and MUC2 was detected by Western blot analysis, while the localization of these proteins within the ileum was examined using immunohistochemistry. Cytometric bead array (CBA) was employed to detect cytokine including IL-6, TNF-α, IL-1β, IL-1α, CXCL-1, MCP-1, IL-17A, IL-18, and IL-33. Flow cytometry analysis was conducted to determine the percentages of Treg cells, M1 macrophages, M2 macrophages, T cells and CD8⁺T cells.

Results

The results showed that compared with the normal gravity groups, the simulated microgravity groups exhibited a significant decrease in RegIII α/γ protein expression, an increase in M1 macrophage frequency, and elevated levels of TNF-α, IL-1α, MCP-1 and IL-6. Notably, the combined application of MXF and CPS effectively mitigated intestinal barrier damage in CLP-rats exposed to microgravity, as evidenced by alleviated ultrastructural and pathological impairments in ileum, along with increased expression of key intestinal barrier proteins MUC2 and RegIII α/γ. Furthermore, the combination therapy enhances the proportion of T cells, CD8⁺ T cells, and M2 macrophages in septic rats exposed to simulated microgravity while reducing the frequency of Treg cells and M1 macrophages. MXF plus CPS also led to a reduction of proinflammatory cytokines and chemokines, including IL-6, TNF-α, IL-1β, IL-1α, CXCL-1, MCP-1, IL18, and IL33.

Conclusion

Our study showed that MXF plus CPS exhibited a protective effect on intestinal barrier damage due to abdominal infection under microgravity, potentially attributed to its anti-inflammatory properties and immune regulatory mechanisms. These findings may provide insights into the development of drugs targeting abdominal infections in the space environment.