Modulation of MAPK/NF-κB Pathway and NLRP3 Inflammasome by Secondary Metabolites from Red Algae: A Mechanistic Study

[Image: see text] The pharmacological properties of seaweeds are diverse. No studies have been conducted on the protective effect of Galaxaura oblongata (GOE) against lippopolysaccharide (LPS)-induced inflammation in the brain. This study is divided into three phases, the first of which is the initial phase. In vitro study includes antioxidant, radical scavenging, and anti-inflammatory activities, including cyclooxygenase-1 (COX1), COX2, NO, acetylcholine inhibition, sphingosine kinase 1, tumor necrosis factor α (TNF-α), and interleukin-6, as well as antioxidant and radical-scavenging activities, including 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid. Using LPS-induced acute inflammation, the second phase was conducted in vivo. Antioxidant and anti-inflammatory assays were performed to investigate the protective role of GOE. In addition to the phytochemical analysis, the bioactive content of GOE was also investigated. In vitro results demonstrated the potential of GOE as an antioxidant, anti-inflammatory, and neuroprotective agent. A study using LPS as an induced lung injury and neuroinflammation model confirmed the in vitro results. The GOE significantly reduced inflammatory, oxidative, and neurodegenerative biomarkers based on histopathological and immuno-histochemistry results. Based on computational drug design, four target proteins were approved: nuclear factor κB, mitogen-activated protein kinases, TNF-α, and NLRP3. Using polyphenolic compounds in GOE as ligands demonstrated good alignment and affinity against the three proteins. Finally, the current study offers a new approach to developing drug leads considering GOE’s protective and curative roles.