## 4 Discussion
Toll-like receptors (TLRs) are the pattern recognition receptors present on the cell surface of innate immune cells including macrophages and are involved in macrophages mediated inflammation in various diseases [73; 74]. Recent studies showed the effects of natural plant compounds in mitigating TLR/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR/NF-kB) signaling to ameliorate inflammation in various disease models [75; 76]. Future studies could be designed to observe the effects of these algal extracts in targeting TLR/NF-kB signaling. Macrophages serve as a double-edged sword dependingupon their external environment, where some are known as classical or inflammatory (M1 phenotype) and others are known as alternative or anti-inflammatory (M2 phenotype) macrophages [77]. Recent studies have focused on using natural compounds to polarize macrophages toward an M2 phenotype to fight against various diseases. Based on the modulatory properties of these algal extracts, they could be studied for their potential to polarize macrophages in various disease models. NO functions as a critical cellular messenger known to be involved in both immune and inflammatory responses. It is involved in both regulatory (immunosuppressive) functions (e.g., the modulation of cytokine response and the inhibition of lymphocyte proliferation) and effector functions, such as tissue destruction (immunopathological) and the killing of microbial pathogens (immunoprotective) [78]. Moreover, [PERSON] et al. demonstrated the antitumor effects of the supernatant derived from fucoidan-stimulated RAW 264.7 and reported the role of NO in imparting antitumor properties in S-180 cells [79]. We also found that SH, UP, and SF extracts were able to induce the activity of both iNOS and NO, which indicated their immune-enhancing properties. Ptgs2 is involved in catalyzing the conversion of arachidonic acid to prostaglandin E2 (PGE2) [10], which plays an essential role in inflammation by activating mast cells and limiting phagocytosis and pathogen killing by macrophages [11; 12; 13]. _Laminaria japonica_ extract has been shown to exert anti-inflammatory effects against UVB-induced inflammation by reducing Ptgs2 and PGE2. In contrast, our findings showed that all three algal extracts could upregulate mRNA expression levels of Ptgs2 and PGE2 protein production.This suggests that brown seaweeds could be used as anti-inflammatory or immune-enhancing agents in different diseases. Macrophage phagocytosis is a crucial step in the treatment of foreign antigens or pathogens. Various studies have highlighted that impaired phagocytosis by macrophages is a critical event that occurs in chronic diseases. [PERSON] et al. demonstrated the effects of edible green seaweed extracts (such as Caulerpa lentilifera) on the phagocytic properties of RAW 264.7 cells [80] and found that beta-glucan, a bioactive component of seaweed, increased the phagocytic activity of RAW 264.7 cells. Like previous findings, our study also found that SH, UP, and SF induce the phagocytic properties of RAW 264.7 cells. In addition to exhibiting immunomodulation properties by inducing pro-inflammatory and anti-inflammatory cytokines expression, these algal extracts also proved their potential in downregulating NO production in the presence of LPS and in reducing LPS-induced cell viability (data shown in Supplementary Materials). These findings indicated the futuristic potential of these compounds as a therapeutic agent in various immunocompromised or inflammatory diseases. Although this study reported the immunomodulatory potential of algal extracts, their effects could also be studied in the future in the presence of disease-causing agents such as LPS, A\(\beta\), or H\({}_{2}\)O\({}_{2}\), which could give a clear idea about the mode of action of these algal extracts under different disease conditions.