Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with complex pathophysiology involving the brain-gut axis. To assess the effects of Wasabia koreana (WK) on IBS, we employed a mouse model of colonic zymosan injection presenting with diarrhea-predominant IBS-like symptoms. Oral WK administration significantly diminished stool score, suppressed colon length and weight change, and minimized body weight loss without affecting food intake. In WK-treated mice, the submucosal thickening and epithelial lining of the colon were inhibited and were similar to those of naïve mice. Infiltration of mast cells into the colon and serum tumor necrosis factor-α levels were markedly suppressed. These effects were comparable to those of sulfasalazine, an anti-inflammatory drug. Furthermore, the number of visceral pain-related behaviors was significantly decreased, and locomotion activities measured in the elevated plus maze and open field tests were significantly increased by WK in a dose-dependent manner compared with amitriptyline, an antidepressant. These changes were accompanied by reduced FosB2 expression in the brain. Taken together, these data suggest that WK may have potential as a medicinal food for IBS by acting on inflammatory diarrhea and neural activity.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder manifesting as unexplained abdominal pain and bowel habit changes. The pathogenesis of post-infectious IBS is associated with gut–brain axis dysfunction, including low-grade colonic inflammation and anxiety-related long-term brain changes. This study analyzed the efficacy of a standardized extract of Dolichos lablab L. extract (DL), a bean species, in an IBS mouse model resembling post-infectious, diarrhea-dominant IBS. Using a zymosan-induced animal IBS model, we found that oral administration of DL significantly attenuated zymosan-induced increases in colonic macroscopic scores and minimized weight loss without affecting food intake. In the DL-treated mice, the mast cell count and tumor necrosis factor-α level in the colon markedly decreased, similar to results in sulfasalazine-treated mice and in mice with lipopolysaccharide-stimulated bone marrow-derived mast cells. The number of visceral pain-related behaviors was much lower in the DL-treated mice. Anxiety-like behaviors significantly improved, comparable to that after treatment with amitriptyline. The c-Fos expression level in the prefrontal cortex was significantly reduced. Our data suggest that DL could be beneficial for treating IBS by acting on the gut and brain.
Background
Irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder, is characterized by chronic abdominal pain and bowel habit changes. Although diverse complicated etiologies are involved in its pathogenesis, a dysregulated gut–brain axis may be an important factor. Red ginseng (RG), a traditional herbal medicine, is proven to have anti-inflammatory effects and improve brain function; however, these effects have not been investigated in IBS.
Methods
Three-day intracolonic zymosan injections were used to induce post-infectious human IBS-like symptoms in mice. The animals were randomized to receive either phosphate-buffered saline (CG) or RG (30/100/300 mg/kg) for 10 days. Amitriptyline and sulfasalazine were used as positive controls. Macroscopic scoring was performed on day 4. Visceral pain and anxiety-like behaviors were assessed by colorectal distension and elevated plus maze and open field tests, respectively, on day 10. Next-generation sequencing of gut microbiota was performed, and biomarkers involved in gut–brain axis responses were analyzed.
Results
Compared to CG, RG significantly decreased the macroscopic score, frequency of visceral pain, and anxiety-like behavior in the IBS mice. These effects were comparable to those after sulfasalazine and amitriptyline treatments. Moreover, RG significantly increased the proliferation of beneficial microbes, including
Lactobacillus johnsonii
,
Lactobacillus reuteri
, and
Parabacteroides goldsteinii
. RG significantly suppressed expression of IL-1β and c-fos in the gut and prefrontal cortex, respectively. Further, it restored the plasma levels of corticosterone to within the normal range, accompanied by an increase in adrenocorticotropic hormone.
Conclusion
RG may be a potential therapeutic option for the management of human IBS.
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