## 4 Discussion  
In this study, we demonstrated that SHE has anti-inflammatory properties by inhibiting the inflammatory markers MPO, TNF-\(\alpha\), IL-6, and IFN-\(\gamma\), and mRNA expression of _Nfkb p65_ and _Cox2_ and the mTOR axis and inducing the mRNA expression of tight junction factors, including _Occludin_ and _Claudin1_, and beneficial bacteria, _Bacteroides_ spp., in in vitro and in vivo colitis models. We confirmed our hypothesis that SHE modulates the mTOR axis and the gut microbiota composition to reduce inflammation in intestinal colitis. UC is a chronic inflammatory bowel disease with increasing prevalence worldwide [50]. Multiple studies have shown that dietary polyphenols may help colitis by modulating the NF-\(\kappa\)B and MAPK pathways and improving the Nrf2 pathway and intestinal dysbiosis [51, 52]. This study identified the carotenoid fucoxanthin, phenol salicortin, and flavonoid vitexin in SHE. Fucoxanthin, mainly found in brown seaweeds, has demonstrated antioxidant and anti-inflammatory properties in inflammatory diseases via inhibition of the NF-\(\kappa\)B/COX-2/PGE2 pathway and downregulation of pro-inflammatory cytokines such as _Nfkb p65_ and _Cox2_. Figure 7: Effects of _S. horneri_ extract (SHE) on the composition of the gut microbiota in DSS-treated mice. (**A**) Shannon index, and (**B**) Faith’s phylogenetic diversity (PD). (**C**) Principal coordinate analysis (PCoA) of weighted UniFrac distances. (**D**) Analysis of the taxonomy community at the phylum and genus levels. (**E**) The Firmicutes to Bacteriodata ratio. (**F–J**) Tax whose relative abundance changed as a result of DSS or DSS-SHE treatment. (n = 3 or 4; fecal DNA from 2 mice was combined for 16S sequencing in a single sample). (**K**) Quantitative PCR for _Akkernansia muciughlin_, (**L**) _Bifidobacterium bifidatum_, and (**M**) _Lactococcus lactis_. The abundance of bacterial groups was quantified as a ratio of total bacteria (F341/F518). All data are expressed as means \(\pm\) SD (\(n\) = 8/group). * \(p\) \(<\) 0.05, ** \(p\) \(<\) 0.01, *** \(p\) \(<\) 0.001, *** \(p\) \(<\) 0.0001 using a nonparametric Kruskal–Wallis test. (**N**) Spearman correlation analysis of gut microbial species and inflammation-related index (* \(p\) \(<\) 0.05, ** \(p\) \(<\) 0.01). CON: control group; DSS: 2.5% DSS in drinking water for the last 7 days; DSS-SHE: DSS + _S. horneri_ extract high dose group (200 mg/kg bw/day). as IL-6 and TNF-\(\alpha\)[53]. In a previous study, fucoxanthin treatment specifically protected DSS-induced mice by preventing body weight loss, increase in DAI, and shortening of the colon, and by reducing the expression of COX-2 and NF-\(\kappa\)B [16]. Salicortin is well-known for its anti-obesity properties, but it also demonstrates anti-inflammatory properties by inhibiting NF-\(\kappa\)b/JNK expression [54]. Vitexin, an apigenin glycoside found in bamboo and mung beans, reportedly possesses antioxidant, anti-inflammatory, and anti-cancer properties [55]. NF-\(\kappa\)B is significantly activated in patients with IBD and has a potent effect on mucosal inflammatory processes [56]. Therapeutic agents used to treat IBD, such as anti-TNF-\(\alpha\) antibodies, sulfasalazine, and methotrexate, are known to inhibit NF-\(\kappa\)B activity [57]. Consequently, this experiment was conducted with the hypothesis that _S. horneri_, with a combination of these substances, would be therapeutic for ulcerative colitis via the suppression of NF-\(\kappa\)B and pro-inflammatory cytokines, and the results were consistent with this hypothesis. We confirmed that SHE reduced _N/Rb_ and _Inos_ mRNA levels and pro-inflammatory cytokines including TNF-\(\alpha\), both in vivo and in vitro. The mTOR pathway is involved in the production of inflammatory cytokines and promotes the progression of colitis [58], which regulates intestinal barrier integrity and plays an essential role in UC remission [59].