*2.3. Dictyophora indusiata Polysaccharide*

*Dictyophora indusiata* polysaccharide (DIP) is isolated from mushrooms with a molecular weight of 1132 kDa. The main linkage-type of DIP including (1→3)-linked α-L-Man, (1→2, 6)-linked α-d-Glc, (1→6)-linked β-d-Glc, (1→6)-linked β-d-Gal, and (1→6) linked β-d-Man. DIP could markedly facilitate the excretion of NO, TNF-α, and IL-6 from macrophages involved in complement receptor 3 (CR3) [22]. DIP has a latent treatment impact against colitis by increasing the level of *Bacteroidaceae* and *Enterobacteriaceae* in the colitis microenvironment. The administration of DSS-induced mice with DIP significantly reduced the pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ) and enhanced antiinflammatory cytokines (IL-4, IL-10) [23]. The treatment of DIP with the DSS-induced mice restrains the biomarker of M1 macrophages CD86. It changed the macrophage subset distribution by reducing the production of M1 subsets from splenic macrophages and made deviate polarization to M2 subsets [24]. The macrophages have a tight connection to the inflammatory cytokines' generation. The M1 macrophages are connected to IL-6 as well as TNF-α, and M2 macrophages are associated with the generation of IL-10 [25]. DIP also can down-regulate the MPO level dramatically in a dose-dependent manner. As an inflammatory marker, the association between MPO and IBD is that it identifies the infiltration of inflammatory cells and tissue damage. Simultaneously, DIP also decreases NO activity and increases T-SOD levels. The latter would give rise to the production of NO [26], which triggers tissue damage and induces inflammatory responses during the occurring of IBD [18].

Recent studies have found that DIP not only decreased endotoxins, including lipopolysaccharides, but also maintained the normal level of tight junction (TJ) proteins expression including claudin-1, occludin, and zonula occludens (ZO)-1 in the antibiotic-induced mice [27]. Broad spectrum antibiotics have been demonstrated to cause gut dysbiosis [28] and destroy epithelial barrier integrity [29], thus raising the hazard of IBD occurrence in the neonates [30]. DIP could restore the function of the gut barrier. The gut mucosal barrier prevents the pathogens and toxins from invasion into the intestine, which has an essential function involved in maintaining the intestine in healthy condition. Additionally, DIP also inhibited the colonic tissue apoptosis in the ulcerative colitis mice by improving the expression of Bcl-2 and Bax [24].

#### *2.4. Flammuliana velutipes Polysaccharids*

Flammuliana velutipes polysaccharides (FVP) are comprised of glucans, galactan, xyloglucan, and xylomannan, whose backbone is α-(1→4)-d-glucose residues with branches consisting of (1→6)-linked α-d-glucopyranosyl [31]. FVP has various bioactivities including immunity regulation [32], anti-oxidant, anti-microbial, anti-tumor properties, and so on [33]. FVP could recover colon injury induced by DSS, and moderate the dysbiosis in the gut microbiota, such as by boosting the *Firmicutes/Bacteroidetes* ratio and enhancing the *Lachnospiraceae* abundance [34]. *Lachnospiraceae* is able to restrain intestinal immune homeostasis via promoting the SCFA production [35], which might explain the phenomenon that FVP increased the production of SCFAs in the gut.

#### *2.5. Pleurotus eryngii Polysaccharides*

Treatment of *Pleurotus eryngii* polysaccharides (PEP) could increase the abundance of *Porphyromonadaceae, Rikenellaceae, Bacteroidaceae,* and *Lactobacillaceae* on C57BL/6 mice. More importantly, PEP increased the SCFA production in the mice colon. SCFAs exert numerous functions in the mice including regulating gut immunity conditions, changing the mucus layer composition and restraining the homeostasis of the intestine [36]. At the same time, PEP inhibited the expression of ROS and NO in RAW264.7 macrophages, and sulphonated PEP showed more powerful anti-inflammatory activity [37].

A water-soluble polysaccharide (EPA-1) isolated from *Pleurotus eryngii* (99.7 kDa) consisting of mannose, glucose, and galactose with the ratio of 2.2:1.0:3.2 EPA-1 not only increased the manufacturing of NO and pro-inflammatory cytokines including TNF-α, IL-1, as well as IL-6, but also exhibited the improved expression level of phosphorylated p38, ERK, JNK, and NF-κB. It reflects the EPA-1 influence inflammatory response via the effect on MAPK and the NF-κB signal mediated pathway [38]. EPA-1 exerts intestine immunity to enhance its protective effect. The immunity cytokines including IL-6 motivated signaling pathways could promote the various leukocytes recruiting and activation [39], which is subsequently followed by possessing invading microorganisms and further diminishment of epithelial damage. Therefore, EPA-1 ameliorates IBD through moderate inflammatory cytokines. Above all these results have indicated that polysaccharides from *Pleurotus eryngii* have the function to alleviate IBD. Therefore, it is thought that PEP reduces the risk of IBD and benefits colitis recovery [40].

#### *2.6. Gracilaria Polysaccharides*

*Gracilaria caudata* polysaccharide consists of 1→3-linked-β-d-galactose and 1→4 linked-3,6-anhydro-α-L-galactose [41] with a molecular weight of 116 kDa [42]. Administrated *G. caudata* polysaccharide could significantly reduce neutrophil infiltration in acetic acid-induced mice via decreasing the expression of MPO levels together with restoring the colon from acetic acid injuries by reducing oxidative stress, including the diminishment of GSH consumption and iNOS expression in the gut [43].

Another species from genus of *Gracilaria* is *Graciliaria lemaneiformis*, the polysaccharides of *Graciliaria lemaneiformis* (SP), which also has sulfated groups. In the mice model developed by Ren et al. [18], SP was orally administrated 200, 400, 600 mg/kg/day for 3 weeks and the arresting weight loss following subsequently by the improved conditions of mice. Histological analysis showed that the colon structure, including the crypt number and muscular structure, was improved by raising the SP dosage, suggesting that a high dose of SP protects the goblet cells and crypt structure in the gut. SP also could repress the intestinal endotoxin and lipopolysaccharide-binding protein production, together with the reduction of TNF-α, IL-6, and IL-1β expression [44]. All of these markers indicate that SP alleviates the symptoms of IBD.

#### *2.7. Blidingia minima Polysaccharides*

*Blidingia minima* often grow in Subei Shoal in China and have similar morphology characteristics as *Enteromorpha* species. Polysaccharides extracted from *Enteromorpha* species have revealed various beneficial functions such as, for instance, anti-inflammatory and antioxidant activities [45]. Recently, Song et al. administrated *Blidingia minima* polysaccharides (BMP) to DSS-induced mice, and found a decrease in the expression of anti-inflammatory cytokine IL-10 and an increase in the production of pro-inflammatory cytokines including IL-1β and TNF-α. The expression of NF-κB, IκB-α, and AKT was also increased, thus, BMP might modulate the motivation of NF-κB and AKT signaling pathway to ameliorate IBD [46].
