Table 1.

Anti-inflammatory bioactive substances derived from seaweed.

Species	Bioactive Compounds/ Extracts/ Purified Compounds	Model	Anti-Inflammatory Activity	Ref.
Eisenia bicyclis	Phlorofucofuroeckol A (compound purified by HPLC and characterized by NMR).	Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.	Suppresses LPS-induced nitric oxide (NO) production at 10 µg/mL. In this study, 10 µM AMT 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine was used as a positive control.	[22]
Ecklonia stolonifera	Phlorofucofuroeckol B (compound purified by HPLC and characterized by NMR).	LPS-stimulated microglial cells.	Inhibits secretion of tumor necrosis factor (TNF) -α, interleukin (IL)-1β and IL-6, downregulates the transcription of cycloxygenase (COX)-2 and iNOS synthase, inhibits IκB-α/NF-κB and Akt/ERK/JNK pathways at concentrations of 10 µM–40 µM.	[23]
Ecklonia cava	Dieckol (compound purified by HPLC and characterized by NMR).	LPS-stimulated microglial cells.	Suppresses LPS-induced mRNA expression of inflammatory mediators COX-2 and iNOS and NO production at concentrations 50 µg/mL to 300 µg/mL. Inhibits IL-1β and TNFα production. Reduces mRNA expression of NF-κB and p38 MAPK.	[24]
Ecklonia cava	Dieckol (commercial dieckol is used in this study).	Carrageenan-triggered inflammation in mice.	Dieckol inhibits carrageenan-triggered inflammation, leukocyte infiltration and formation of pro-inflammatory regulators such as TNFα, IL1β, IL6, etc. at dosages from 5 mg/kg–20 mg/kg bodyweight.	[25]
Ishige okamurae	Diphloretho- hydroxycarmalol purified from aqueous methanol extract through HPLC and characterized by NMR.	LPS-induced RAW 264.7 cells and TNF-α-stimulated C2C12 myotubes.	Downregulates mRNA expression of pro-inflammatory cytokines, reduces NO production and reduces protein expression of NF-κB and p38 MAPK at concentration ranges from 6 to 200 µg/mL.	[26]
Ishige okamurae	Diphloretho- hydroxycarmalol purified from aqueous methanol extract through HPLC and characterized by NMR.	LPS-stimulated RAW 264.7 macrophages.	Downregulates IκB-α and NF-κB protein expression and inhibits IL-6 production by downregulating STAT5 activation and SOCS1 augmentation at concentration ranges from 12.5 to 100 µM.	[27]
Ishige foliacea	Octaphlorethol A purified from aqueous ethanolic extract and characterized by LC/MS and NMR.	CpG- stimulated C57BL/6 mice bone-marrow-derived macrophages and bone-marrow-derived dendritic cells.	Exhibits anti-inflammatory activity by octaphlorethol A by transcriptional regulation of NF-κB through MAPK at concentration ranges from 1.5 to 50 µM.	[28]
Saccharina japonica	Fucoidan purified from ethanolic extract by dialysis and HPLC.	LPS-stimulated RAW 264.7 macrophages and LPS-induced zebrafish embryonic cells.	Reduces the production of NO and downregulates the expression of MAPK (including p38, ENK and JNK) and NF-κB (including p65 and IκBα/ IκBβ) signaling pathways at concentration ranges from 12.5 to 50 µg/mL.	[29]
Colpomenia sinuosa	Fucoidan purified from ethanol:formaldehyde:water solvent system through acid extraction and purification.	In vitro NO scavenging assay and RBC hemolysis and PCM-induced hepatic injury in rat.	Prevents paracetamol-induced hepatic oxidative stress and decreases NO, iNOS, TNFα, IL-1β and IL-6 in liver tissue at a concentration of 10 to 50 µg/mL.	[30]
Fucus vesiculosus	Fucoidan from Fucus vesiculosus purchased from Sigma.	LPS-stimulated RAW 264.7 macrophages and LPS-induced zebrafish embryonic cells.	Decreases secretion of NO, prostaglandin (PG) E2, TNFα and IL-1β at concentration ranges from 0.5 to 10 µg/mL.	[31]
Fucus vesiculosus	Fucoidan crude hot water extract.	UV-induced inflammation in HaCaT cells.	Decreases production of NO, PGE2, IL-1β and TNFα, and inhibits NF-κB, Akt, ERK, p38 MAPK and JNK pathways regulated by nc886-PKR.	[32]
Sargassum fulvellum	Sulfated polysaccharides purified from ethanolic extract by HPLC.	LPS-stimulated RAW 264.7 macrophages and LPS-induced zebrafish embryonic cells.	Suppresses production of NO, TNFα, IL-1β and IL-6, downregulates expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells, improves survival rate and reduces cell death, reactive oxygen species (ROS) and NO in LPS-stimulated zebrafish at concentration ranges from 25 to 100 µg/mL.	[33]
Sargassum horneri	Alginic acid purified from ethanolic extract by HPLC and GC/MS.	LPS-stimulated RAW 264.7 and human haCaT cells and particulate-matter-stimulated inflammation in keratinocytes and fibroblasts	Suppresses PGE2 production via COX-2 inhibition, decreases pro-inflammatory cytokines and abates NF-κB and MAPK pathways in the model system at concentration ranges from 50 to 125 µg/mL.	[34]
Grifola frondosa	Laminarin purified from water extract by dialysis.	LPS-stimulated RAW 264.7 macrophages.	Inhibits NO and PGE2 production, suppresses pro-inflammatory cytokine (TNF-α and IL-6) secretion and inactivates NF-κB pathway at concentration ranges from 50 to 200 µg/mL.	[35]
Padina boryana	Fucosterol purified from ethanolic extract by HPLC.	Particulate matter and LPS-stimulated RAW 264.7 macrophages.	Inactivates NF-kB and MPAK pathways and suppresses iNOS, COX-2, pro-inflammatory cytokines and PGE2 mRNA expression at concentration ranges from 12.5 to 50 µg/mL.	[36]
Stypopodium flabelliforme	Epitaondiol purified from marine metabolite.	In vitro sPLA2 activity, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model.	Inhibits phospholipase A2 production, suppresses eicosanoid (LTB4 and TXB2) release and reduces TPA-induced mouse ear inflammation at approximately 3.8 µM.	[37]
Laurencia glandulifera	Neorogioltriol purified from many solvent fractions by HPLC.	LPS-stimulated RAW 264.7 macrophages, DSS-induced colitis in mice.	Suppresses macrophage activation, promotes M2-like anti-inflammatory phenotype and suppresses DSS-induced colitis by reducing tissue damage and pro-inflammatory cytokine production.	[38]
Dunaliella tertiolecta	Ergosterol purified from lipid extract by HPLC and analyzed by GC/MS.	LPS- and ConA-stimulated sheep peripheral blood mononuclear cells.	Inhibits pro-inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10) production at concentration of 0.2 to 0.8 mg/mL.	[39]
Sargassum muticum	Apo-9′-fucoxanthinone.	LPS-stimulated RAW 264.7 macrophages and LPS-induced zebrafish embryonic cells.	Suppresses mRNA expression of inflammatory mediators such as iNOS, COX-2 and pro inflammatory cytokines, and modulates NF-κB and MPAK signaling pathways	[40]
Amansia multifida	Lectin purified by sodium salt extraction and HPLC.	Carrageenan-triggered inflammation models in rat.	Reduces parameters of the inflammatory process such as edema formation and leukocyte migration, and modulates levels of proinflammatory cytokines, IL-1β and TNF-α.	[41]
Bryothamnion triquetrum	Lectin.	Carrageenan-triggered inflammation in rat.	Inhibits vascular and cellular events of an acute inflammatory response, and inhibits neutrophil migration to inflammation sites via suppression of TNF-α and IL-1β production at different concentrations in different models.	[42]
Ulva spp.	Peptide fractions purified from enzyme hydrolysate and characterized by FPLC.	LPS and ConA-stimulated rat spleen mononuclear cells.	Modulates TLR4 and the NFκB/p38/JNK pathway at 0.01 g/L to 0.1g/L.	[43]
Caulerpa peltata, Caulerpa racemosa	Caulerpin purified from ethanolic extract and crystalized from liquid portioning.	DSS-induced colitis in mice.	Reduces inflammatory infiltrates and the levels of the proinflammatory cytokines, increases the levels of the anti-inflammatory cytokine IL-10 and suppresses NF-κB p65 expression.	[44]
Gracilaria opuntia	Azocinyl morpholinone alkaloid purified from ethanol:methanol extract by HPLC.	Carrageenan-triggered inflammation in rat. In vitro anti-inflammatory model using 5-LOX inhibition assay.	Reduces edema formation by 6 h and exhibits a selective inhibitory effect on COX-2 and 5-LOX activity at a concentration of approximately 0.08 mg/mL.	[45]
Ulva pertusa	3-Hydroxy-4,7-megastigmadien-9-one purified from aqueous ethanol extract by MPLC.	CpG-stimulated C57BL/6 mice bone-marrow-derived dendritic cells.	Inhibits IL-12 p40, IL-6 and TNF-α production and blocks MAPKs and NF-κB pathways at concentration ranges from 0.1 to 50 µM.	[46]
Laelia undulata	Floridoside purified from methanolic extract by thin-layer chromatography.	LPS-stimulated BV-2 microglia cells.	Inhibits the production of NO and ROS and downregulates the protein and gene expression levels of iNOS and COX-2 by significantly blocking the phosphorylation of p38 and ERK in LPS-stimulated BV-2 cells at concentration ranges from 10 to 50 µM.	[47]
Cymopolia barbata	Cymopol and cyclocymopol purified from various non-polar extract through HPLC.	DSS-induced colitis in mice, zebrafish tail wound model and RAW 264.7 macrophages.	Attenuates neutrophil migration and reduces the colon inflammation at the in vitro concentration of 1 to 3 µM and 0.1 to 0.4 g/kg body weight.	[48]
Sargassum siliquastrum	Sargachromanol G isolated from aqueous methanol and other solvent and then purified from HPLC.	LPS- and RANKL-stimulated RAW 264.7 macrophages	Reduces the expression of pro-inflammatory cytokines, suppresses NO and PGE2 production via inhibition of iNOS and COX-2 and inhibits RANKL-induced activation of NF-κB by suppressing RANKL-mediated IκB-α degradation at concentration ranges from 10 to 40 µM.	[49,50]