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.