Pertiwi F. Chandrawati, Loeki E. Fitri, Valentina Yurina, Akhmad Sabarudin, M. Izdad I. Fanada, Hanifa R. Rahmawati
Brown seaweed is hypothesized to possess antihyperlipidemic properties due to its Cholesterol 7α-hydroxylase (CyP7A1) and 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) activity. This study aims to elucidate the mechanisms of brown seaweed compounds as antihyperlipidemic. Major bioactive compounds of brown seaweed, including fucoidan, fucoxanthin, laminarin, and sodium alginate were analyzed using structure–activity relationship analysis. Putative protein targets were predicted using PASS Protein Target, SEA, and the Comparative Toxicogenomics Database, while hyperlipidemia-related targets were obtained from GeneCards, Open Targets, DisGeNET, and PharmGKB. Protein–protein interaction network was constructed to screen out the hub genes using STRING-DB and Cytoscape software. Human CYP7A1 and HMGCR structures were retrieved from the RCSB PDB, with cholestyramine and mevastatin as reference ligands. Molecular docking was performed using PyRx, followed by molecular dynamics simulations with YASARA to assess complex stability. Network pharmacology analysis identified HMGCR as a direct molecular target, while CYP7A1 was indirectly regulated through upstream mediators, including peroxisome proliferator-activated receptor alpha (PPARα), cytochrome P450 2E1 (CYP2E1), and fibroblast growth factor receptor (FGFR4). Fucoidan-HMGCR and fucoxanthin–HMGCR complexes showed stable binding energies, persistent hydrogen bonding, and minimal conformational fluctuations. Additionally, brown seaweed compounds modulated key inflammatory and lipid metabolism–related pathways involving interleukin 6 (IL-6), tumor necrosis factor (TNF), IL-1β, AKT serine/threonine kinase 1 (AKT1). IL-10, prostaglandin G/H synthase 2/cyclooxygenase 2 (PTGS2), nuclear factor kappa-light-chain enhancer of activated B cells 1 (NF-κB1), peroxisome proliferator-activated receptor gamma (PPARγ), PPARα and glutamic-pyruvic transaminase (GPT). In conclusion, brown seaweed bioactive compounds show significant potential as natural antihyperlipidemic agents through HMGCR and CYP7A1. © 2026 Chandrawati et al.
Department of Pediatric, Faculty of Medicine, Muhammadiyah University, Malang, Indonesia; Doctoral Program in Medical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Clinical Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Pharmacy, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Chemistry, Faculty of Science, Universitas Brawijaya, Malang, Indonesia; RSUD Kota Malang, Malang, Indonesia; Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
