# Phytosterols in Seaweeds: An Overview on Biosynthesis to Biomedical Applications
## 4 Health Benefits and Biomedical Applications of Phytosterols
### Phytosterols as Anti-Inflammatory Agents  
Chronic inflammation generally develops as part of the sequence of cellular events following acute inflammation in humans and animals. The important microcirculatory responses, including the recruitment of leukocytes, vascular permeability modulation, and releasing inflammatory mediators, are responsible for developing and maintaining inflammation [89; 90]. The inflammatory cytokines, including tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)), cyclooxygenase (COX-2), interferon gamma (IFN\(\gamma\)), interleukin (IL)-1\(\upmu\)g, IL-6, IL-8, and IL-10, are the key modulators of low-grade chronic inflammation [91; 92]. Lipopolysaccharide (LPS) triggers an immune response by interacting with the membrane receptor to enhance the production of cytokines. The excessive production of such inflammatory mediators contributes to chronic inflammatory disorders. Chronic inflammation has been subjected to the physiopathology of several diseases, including cancer, hepatitis, obesity, diabetes, metabolic syndrome, arthritis, degenerative neurological disorders, and cardiovascular diseases [93]. Several bioactive natural compounds have shown anti-inflammatory activity to protect against chronic diseases. Recently, numerous anti-inflammatory agents have been isolated from marine algae with protective efficacy against chronic inflammation [94; 95]. In particular, the mechanisms involved in counteracting neuroinflammation include inhibiting the expression of pro-inflammatory enzymes [96], reducing inflammatory mediators, modulating MAPK pathways [97], and NK-kB activation [98]. Among the marine algae derivatives, phytosterols have been described as efficient anti-inflammatory agents. Among chronic inflammations, inflammatory bowel diseases (IBDs) cause serious problems in younger generations, as they cause serious illnesses and are proven to be fatal, if untreated [99]. In the hunt for natural compounds to treat such inflammations, phytosterols had been proven to augment the clinical remission of IBDs in mice [100]. However, there is no report that can link these effects to macroalgae-derived phytosterols. Fucosterol and its derivatives are the most common phytosterols, majorly found in brown seaweed [7]. Several studies have investigated the anti-inflammatory potential of fucosterol and its derivatives. For instance, fucosterol, isolated from the brown seaweed _E. bicyclis_, has been shown to attenuate the expression of inflammatory mediators such as inducible nitric oxide (NO) synthase and COX-2 in LPS-stimulated macrophages [66]. [PERSON] et al. [101] also reported that fucosterol shows anti-inflammatory activity by suppressing TNF-\(\alpha\), IL-6, and IL-1\(\upmu\) expressions. Fucosterol also attenuates the LPS-induced inflammatory response by suppressing the production of TNF-\(\alpha\), IL-6, and IL-1\(\upmu\)g and nuclear factor-kB (NF-kB) activation in LPS-induced alveolar macrophages [102]. NF-\(\upmu\)g has been considered a prototypical pro-inflammatory signaling pathway. The activation of the NF-\(\upmu\)g, by nuclear translocation of cytoplasmic complexes, plays a key role in inflammation via the induced transcription of genes encoding pro-inflammatory mediators [103]. Also, the anti-inflammatory agent fucosterol has been isolated from the most abundant marine brown algae, _S. binderi_. [PERSON] et al. [71] have reported that the fucosterol from _S. binderi_ inhibited chronic inflammatory responses by suppressing the production levels of TNF-\(\alpha\) and IL-6, COX2, and prostaglandin E2, the nuclear translocation of both p65 and p50, and the activation of the p38 mitogen-activated protein kinase (MAPK) pathway [71]. Alzheimer's disease, inflammatory bowel disease, and rheumatoid arthritis are postulated to be synchronized, in part, by MAPK p38 [104; 105; 106].