Fucosterol’s modulatory effects on interleukin-6 and interleukin-1β: insights from molecular docking and lipopolysaccharide-induced HEK293 cells and zebrafish embryos

Chronic inflammatory diseases remain among the leading causes of death worldwide, highlighting the need for safer and more cost-effective anti-inflammatory agents from natural resources. Fucosterol, a bioactive compound isolated from brown marine algae, has been reported to exhibit various pharmacological properties, including anti-inflammatory activity. However, further investigation is needed to elucidate its mechanisms of action. This study assessed the anti-inflammatory potential of fucosterol using in silico, in vitro, and in vivo approaches. Reverse molecular docking revealed strong binding affinities with interleukin (IL)-6 (–6.3 kcal/mol) and IL-1β (–7.4 kcal/mol), suggesting potential interactions with key inflammatory cytokines. Moreover, absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling highlighted fucosterol’s favorable drug-likeness and toxicity profile. Toxicity assessments, including the MTT assay on Human Embryonic Kidney (HEK293) cells and the zebrafish embryo acute toxicity assay, showed concentration-dependent effects, with half-maximal inhibitory concentration (IC50) and medial lethal concentration (LC50) values of 279.90 μg/mL and 173.60 μg/mL, respectively. In vitro Enzyme-Linked Immunosorbent Assay (ELISA)-based assay using lipopolysaccharide-induced HEK293 cells demonstrated a biphasic response in inhibiting IL-6 (24 and 48 h IC50 = 5.86 and 73.36 μg/mL) and IL-1β (24 and 48 h IC50 = 2.59 and 0.02 μg/mL). Similarly, in vivo analysis using lipopolysaccharide-induced zebrafish embryos showed a significant reduction in IL-6 (24 and 48 h IC50 = 34.54 and 30.28 μg/mL) and IL-1β (24 and 48 h IC50 = 29.39 and 29.61 μg/mL) at higher concentrations. These findings provide valuable insights into fucosterol’s role in modulating inflammatory cytokines, likely through the NF-κB pathway. The study provides a better understanding of fucosterol’s anti-inflammatory mechanisms, supporting its potential for further pharmacological research. Future studies, including clinical validation and mechanistic studies, are necessary to establish its therapeutic use and application.