Effects of red ginseng on gut, microbiota, and brain in a mouse model of post-infectious irritable bowel syndrome

Abstract

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.

Suppression of PTRF Alleviates Post-Infectious Irritable Bowel Syndrome via Downregulation of the TLR4 Pathway in Rats

“…The PI-IBS model rats in our experiments showed greater levels of tension and anxiety, among other emotions. The body weight of these animals decreased with the increased fecal water content, and there was a significant decrease in sucrose preference after EPSD treatment, which is consistent with the results of previous studies (Yu et al, 2021). AAV-mediated PTRF knockdown increased the body weight and sucrose preference, which coincided with the decreased fecal water content.…”

Brain plasticity and ginseng

“…Gut microbiome communicate bi-directionally with the brain through the 'gut-brain axis,' influencing neuroplasticity [ 13 ]. Ginseng has been reported to impact gut bacteria and alter cognitive function in animals [ 69 , 70 ]. One clinical study related to ginseng consumption and gut microbiome composition has been reported in healthy adults.…”

“…In Table 2 , recent literatures published within the past three years that can help to understand the molecular mechanisms through which ginseng acts in brain plasticity are summarized. Ginseng has influenced brain plasticity by affecting various cells within the central nervous system, including neurons [ 41 , 56 , [73] , [74] , [75] , [76] , [77] , [78] ], oligodendrocytes [ [79] , [80] , [81] , [82] ], astrocytes [ 83 , 84 ], microglia [ 82 , 85 ], and peripheral systems such as gut microbiota [ 69 , 70 , 86 ]. In terms of molecular level, the effects of ginseng have been observed in the altered levels of neurotransmitters (such as serotonin [ [73] , [74] , [75] , 86 ], dopamine [ 74 , 86 ], and gamma-aminobutyric acid (GABA) [ 73 ]), N-methyl- d -aspartate receptor (NMDAR) subunits [ 76 ], synaptic proteins [ 56 ], and Brain-Derived Neurotrophic Factor (BDNF) [ 56 , 73 , 74 ].…”

“…In terms of molecular level, the effects of ginseng have been observed in the altered levels of neurotransmitters (such as serotonin [ [73] , [74] , [75] , 86 ], dopamine [ 74 , 86 ], and gamma-aminobutyric acid (GABA) [ 73 ]), N-methyl- d -aspartate receptor (NMDAR) subunits [ 76 ], synaptic proteins [ 56 ], and Brain-Derived Neurotrophic Factor (BDNF) [ 56 , 73 , 74 ]. It has induced anti-oxidation [ 41 , 74 ] and anti-inflammation [ 56 , 70 , 85 ], increased mitochondrial function and biogenesis [ 78 , 83 ], enhanced the functions of astrocyte gap junctions [ 84 ], and the BBB [ 69 ]. Moreover, ginseng was involved in cell proliferation and differentiation [ 79 , 80 , 83 , 84 ].…”

“…Moreover, ginseng was involved in cell proliferation and differentiation [ 79 , 80 , 83 , 84 ]. Through these complex cellular and molecular mechanisms, ginseng has promoted brain plasticity and enhanced brain functions, including reductions in anxiety [ 70 , 73 , 76 , 86 ] and depression [ 75 , 84 , 86 ], and improvements in cognition [ 56 ], learning [ 41 ], memory [ 41 , 56 , 85 ], and sociality [ 76 ].…”