## 3 Results  
### LC-MS Analysis of EB Extracts  
The LC-MS analysis revealed distinct profiles for different extracts. In the EB-Met extract, we identified the presence of 7-phloroechol, phloroofucofluoecol A, and Dieckol (Figure 1A). Similarly, the EB-EtOAc extract contained 7-Phloroeckol, Phloroofucofuroecolol A, and Dieckol, with significantly elevated quantities by 334%, 250%, and 140%, respectively, compared to the EB-Met extract, indicating a richer phlorotannin fraction (Figure 1B). Additionally, the detection of phloroglucinol was confirmed in the EB-EtOAc extract. Upon fermentation, the EB-EtOAc extract exhibited an even more pronounced increase in phloroglucinol content along with the presence of 7-phloroechol and phloroofucofuroecol A (Figure 1C). This observation suggests a synergistic effect, with the fermented EB-EtOAc extract displaying the highest augmentation in phlorotannin levels compared to both EB-Met and non-fermented EB-EtOAc extracts. Notably, EB-EtOAc stood out for its diverse range of phlorotannins. Overall, our findings confirm the extraction of a phlorotannin-rich fraction, with the fermented EB-EtOAc extract demonstrating the most substantial increase in phloroglucinol content (Table 1). Figure 1: Representative LC-MS analysis results displayed in chromatogram. **(A)**_E. bicyclis_ 80% methanol extract (EB-Met); **(B)**_E. bicyclis_ ethyl acetate extract (EB-EtOAc); **(C)** fermented EB-EtOAc extract with _Lactobacillus casei_ for 24 h. Peak 1: Phloroglucinol; Peak 2: 7-Phloroeckol; Peak 3: Phloroofucofuroecolol A; Peak 4: Dieckol. Anti-Inflammatory Effects of Phlorotannins Isolated from E. bicyclis and Fermented Phlorotannins with Lactic Acid Bacteria Species  
To investigate the isolation conditions and anti-inflammatory effects of high-purity phlorotannins from _E. bicyclis_, an experiment was conducted using LPS-treated RAW264.7 cells. The in vitro experiments tested the fractionation of phlorotannins from _E. bicyclis_, expressed as EB-Met or EB-EtOAc, based on the extraction conditions. In comparison to the PC group, TNF-\(\alpha\) exhibited reductions of 21.3% and 35.5% in EB-Met (25 and 50 \(\mathrm{\SIUnitSymbolMicro m}\)/mL, respectively), and 33.7% and 52.0% in EB-EtOAc (25 and 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL, respectively). Notably, the reduction in inflammation was significantly higher in EB-EtOAc at 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL (Figure 2A). IL-6 also showed reductions of 28.8% and 37.2% in EB-Met (25 and 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL, respectively), and 36.7% and 40.9% in EB-EtOAc (25 and 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL, respectively; Figure 2B). EB-EtOAc, representing a phlorotannin-rich fraction, consistently demonstrated superior anti-inflammatory effects compared with the EB-Met extract at all concentrations, exhibiting significant effects even at low concentrations. Utilizing a fractionation process to obtain high-purity phlorotannins, we identified EB-EtOAc, distinguished by its remarkable anti-inflammatory effects, and abbreviated it as TA. To explore potential synergistic effects with lactic acid bacteria, TA and the four selected strains were fermented for a 24 h period. Subsequently, the filtered extracts displayed a significant reduction in inflammation compared to that in the PC group. Compared to the PC group, the TNF-\(\alpha\) levels exhibited reductions of 28.3% in TA, 24.3% in TA + LA, 52.1% in TA + LB, 50.7% in TA + LC, and 28.6% in TA + LP at a concentration of 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL. Specifically, the levels of TNF-\(\alpha\) in the TA + LB and TA + LC groups were significantly lower than those in the TA group (Figure 2C). Similarly, compared to the PC group, the IL-6 levels decreased by 29.3% in TA, 28.7% in TA + LA, 44.9% in TA + LB, 56.4% in TA + LC, and 39.0% in TA + LP at a concentration of 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL. The level of IL-6 in the TA + LC groups was significantly lower than those in the TA group (Figure 2D).