4. Discussion
Inflammatory bowel disease (IBD) is a kind of chronic, nonspecific intestinal inflammation, which includes ulcerative colitis and Crohn’s disease. Acetaminophen and non-steroidal anti-inflammatory drugs are the primary clinical treatment, but long-term usage of these can cause kidney and digestive system damage. It is urgent to develop effective treatment strategies, including therapeutics and functional foods.
ginseng is a perennial herb. Modern pharmacological studies have shown that P. ginseng has therapeutic effects on intestinal system diseases, such as ulcerative colitis, Crohn’s bowel disease and intestinal cancer (Luo, Xu, Zhang, Di, & Shan, 2020). The polysaccharide is an important active component of P. ginseng in mediating the inflammatory response and immune function and has obvious inhibitory effects on many pathogenic bacteria (Guo, Shao, Wang, Zhao, & Wang, 2020). In this study, polysaccharide from P. ginseng was isolated and simi-purified, and its basic physicochemical properties were studied by HPLC, FT-IR, and GPC. The morphology of the polysaccharide was also characterized by SEM analysis. Further, the activity of GP on intestinal inflammation was evaluated by a model of DSS-induced intestinal inflammation in rats. Our results showed that the weight loss of rats in the GP treatment group was inhibited, and the intestinal mucosa loss as well as the infiltration of inflammatory cells in the lamina propria was reduced in the treatment group after the administration of GP. This indicates that GP has a therapeutic effect on DSS-induced colitis in rats, but the specific mechanism is still unclear.
There are at least 1014microorganisms that reside in human intestines which are involved in the host’s immune response, metabolism, and homeostasis maintenance (Michielan & D’Incà, 2015). A large number of clinical and experimental studies have shown that many natural plant polysaccharides can play a therapeutic role in intestinal inflammation by regulating the imbalance of gut microbiota (Sun et al., 2020). Similar results were found in this study: compared with the normal group, the model group of rats had obvious intestinal flora imbalances, while the administration of GP caused a recovery effect on the gut microbiota in model rats. Compared with the model group, the abundance of Gram-negative bacteria decreased significantly after GP administration. It is clear that inflammatory bowel disease is closely related to the regulation of the structure and composition of the intestinal microbiota; however, the pathways involved in the regulation and how to remedy the change in intestinal flora still required elucidation. At present, although there are reports that polysaccharides from P. ginseng can regulate intestinal flora and play a therapeutic role in inflammatory bowel disorders such as IBD and UC, this conclusion overemphasizes the role of intestinal flora and fails to describe the causal mechanism of intestinal flora in the process of disease treatment.
Gut microbiome disorder is closely related to the incidence of a variety of intestinal diseases. In the pathological state of inflammatory bowel disease, the chronic accumulation of activated neutrophils, macrophages, and dendritic cells leads to a change in intestinal flora structure, especially the proliferation of many Gram-negative opportunistic pathogens. Lipopolysaccharide (LPS) is an essential component of the cell wall of Gram-negative bacteria that is involved in triggering the inflammatory cascade (Barker, 2014). TLR4 is the receptor for LPS and is of great importance to the self-repair of intestinal epithelial cells (Jun et al., 2020). Activated TLR4-induced phosphorylation of IκBα via the downstream signaling molecule MyD88 eventually leads to the translocation of NF-κB and the release of cytokines including IL-lβ, IL-8 and TNF-α. TNF-α is an important initiator of inflammation, which can cause a microcirculatory disturbance of colonic mucosa and weaken the mucosal barrier, leading to mucosal damage and inflammatory cell infiltration (Sands & Kaplan, 2007). Clinical studies also confirm that the level of TNF-α in serum is positively correlated with the severity of IBD (Pezelj-Ribarić, Magasić, Prpić, Miletić, & Karlović, 2007). IL-1β increases the cytokines produced by macrophages, such as IL-6, TNF-α, and IL-8, which can promote the aggregation of neutrophils to inflammatory sites and then cause intestinal mucosal tissue damage as well as an intestinal inflammatory response (P. Wu, Guo, Jia, & Wang, 2015). Thus, blocking the TLR4 pathway is an alternative strategy for the development of anti-intestinal inflammation drugs or functional foods (De Jager et al., 2007). In our study, GP markedly suppressed DSS-increased expression of TLR4 and reduced the recruitment of downstream proteins, which was accompanied by decreased cytokines and also the repairment of intestinal mucosa. Our data confirmed that the therapeutic effect of GP on intestinal inflammation is associated with the downregulation of TLR4 expression Fig. 9.