Exploring the anti-inflammatory bioactive metabolites of some marine algae through integration of metabolomics, network pharmacology and molecular docking analyses

Marine algae are well-acknowledged as a prime store of largely unexplored extraordinary chemical entities potentially ameliorating against inflammation however, the efficacy mechanism remains elusive. This study offers an integrated strategy of several bioinformatics and computational tools as well as bio-guided fractionation, and multi-step experimental validations integrated with metabolomics to systematically provide a shortcut of potentially active anti-inflammatory biomarkers of seaweeds. Firstly, multi-level network model of “multi-components-multi-targets-multiple pathways” was established. Complementarily, an in vitro anti-inflammatory testing was estimated via monitoring release of pro-inflammatory mediators. Bioassay-guided fractionation of S. platensis integrated with UPLC-MS analysis of the most promising enriched fractions in terms of anti-inflammatory efficacy were undertaken. Molecular docking studies on the top enriched targets were ultimately conducted. Multi-level network analysis illuminated that the intricate pharmacological mechanisms underlying inflammation mitigation was the knockout of the crucial targets of TLR2, AKT1 and PRKCA and further regulation of principal pathways as PI3K-Akt signaling pathway, arachidonic acid (AA) metabolism and Toll-like receptor signaling pathway. In vitro testing, S. platensis exhibited the greatest potency. UPLC-MS analysis of Spirulina active fractions showed linolenic acid, hydroxy linolenic acid, eicosapentaenoic acid, catechin and carnosic acid were efficacy constituents for mitigating inflammation. Molecular docking showed that eicosapentaenoic, hydroxy linolenic acid and carnosic acid displayed favorable molecular binding capacity to TLR2, AKT1 and PRKCA. Our rationally developed workflow offered the convincing evidence marine algae armed with an arsenal of weapons to regain the harmony disturbed in inflammatory disorders by multi-targeted synergistic functions. [Display omitted]