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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., Graphical abstract Image 1

So-ochim-tang-gamibang (SOCG) is a Korean traditional medicine; it has previously been shown to be safe and effective against depression. Persistently increased levels of circulating glucocorticoids have been considered as a pathological mechanism for depression and associated with decreased neurotrophic factors in the hippocampus. This study investigated whether SOCG controls the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and the molecular mechanisms underlying its effects in vivo and in vitro. Wistar Kyoto (WKY) rats were subjected to restraint stress, where SOCG was orally administered to the animals for 2 weeks. An open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were performed to explore the antidepressant activity of SOCG in WKY rats. Plasma levels of HPA axis hormones were measured by ELISA or western blotting analysis. The expression levels or activation of HPA axis-related signaling molecules such as brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), extracellular regulated kinase (ERK), and glucocorticoid receptors (GRs) in the brain were determined by real-time PCR and western blotting analysis. Furthermore, a corticosterone- (CORT-) induced cell injury model was established using SH-SY5Y cells to explore the antidepressive effects of SOCG in vitro. The results of the OFT, FST, and SPT revealed that SOCG ameliorated depressive-like behaviors in the WKY rats. The blood plasma levels of HPA axis hormones such as CORT, CORT-releasing hormone (CRH), and adrenocorticotrophic hormone were downregulated by SOCG. On the other hand, SOCG upregulated the phosphorylation of CREB and ERK in both the rat hippocampus and CORT-treated SH-SY5Y cells. Moreover, it also increased the GR expression. These results suggested that SOCG may improve depression by controlling hyperactive glucocorticoid signaling via the downregulation of HPA axis hormones and upregulation of GR.

Ethnopharmacological relevance So-ochim-tang-gamibang (SOCG) is a Korean herbal medicine formula that has been applied to treat depressive moods and depression associated somatoform pain. This decoction consists of Cyperus rotundus L. (Cyperi Rhizoma), Lindera aggregata (Sims) Kosterm. (Linderae Radix), Aquilaria agallochum (Lour.) Roxb. ex Finl. (Aquilariae Resinatum Lignum), Glycyrrhiza uralensis Fisch. (Glycyrrhizae Radix) Platycodon grandiflorum (Jacq.) A. DC. (Platycodi Radix), and Citrus aurantium L. (Aurantii Fructus). The aim of this study is to assess antidepressant-like effects of SOCG and to investigate its possible cellular and molecular mechanisms. Material and methods Using chronic restraint stress animal model, effects of SOCG on depressive-like behaviors, corticosterone, and hippocampal expressions of a neurotrophic factor and an apoptotic marker, were investigated. Mice were exposed to restraint stress 6 h per day over a period of two weeks, and orally administrated either SOCG (30, 100, or 300 mg/kg/day). The depressive-like behaviors were analyzed by forced swimming test and open field test. The serum levels of corticosterone were measured by enzyme-linked immunosorbent assay. Expressions of caspase-3 and BDNF in the hippocampus were analyzed by immunofluorescence. Further, effects of SOCG were examined in corticosterone-treated PC12 cells. Cellular toxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. Real-time PCR was applied to investigate the cellular expression levels of Bax, Bcl-2, and BDNF. The levels of caspase-3 and BDNF were examined by Western blotting. Results Administration of SOCG not only reduced immobility time of restraint-stressed mice in a dose-dependent manner, but also significantly increased the distance mice moved and the number of crossings in the open field test. Further, SOCG significantly reduced the serum level of corticosterone and expression of caspase-3, while increased expression of BDNF in vivo. SOCG increased cell viability in corticosterone treated PC12 cells, which was accompanied by decreased caspase-3 expression and the ratio of Bax/Bcl-2 mRNA expression as well as increased BDNF expression in vitro. Conclusions Taken together, our data suggested that SOCG may have potential as an antidepressant agent controlling depressive behaviors and corticosterone-induced neuronal damage caused by chronic stress.

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&ndash, 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-&alpha, 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.

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 naive 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.