Table 1.

Resume of the main anti-inflammatory potential disclosed for seaweeds specialized metabolites.

Compound (Number)	Source *	Concentration Tested	Experimental Model	Pharmacological Markers
Phloroglucinol (1) 1 [40]	Ecklonia cava	10 μΜ	RAW 264.7 cells HT1080 cells	↓ TNF-α, IL-1β e IL-6, PGE2 Inhibit MMP-2 and MMP-9
Dieckol (2) 2 [42,47]	Eisenia sp.	10 and 20 μΜ	HUVECs Mice treated by high mobility group box 1 protein (HMGB1)	↓ LPS-mediated hyperpermeability (74.9%) ↓ LPS-induced HMGB1 release ↓ acetic acid induced-hyperpermeability and carboxymethylcellulose-induced leukocytes migration (55%)
Eckol (3) 3 [43]	Eisenia sp. Eckonia sp.	1–10 μΜ	Propionibacterium acnes induced HaCaT cells	↓ TNF-α ↓ COX-2, iNOS
Phlorofucofuroeckol B 4 (4a) [45]	Eisenia arborea	75 μΜ	ICR strain mouse	inhibition of ear edema induced by AA (42.2%), by TPA (38.4%), and by OXA (41.0%). EGCG inhibits 12.9%, 13.8%, and 5.7% of ear edema induced by AA, TPA, and OXA, respectively
Phlorofucofuroeckol A 5 (4b) [41,45]	Eisenia arborea Ecklonia stolonifera Okamura 1913 a	40 μΜ 10 μΜ 75 μΜ	LPS-stimulated BV-2 cells RBL-2H3 cells ICR strain mouse	↓ TNF-α, IL-1β e IL-6 ↓ COX-2, NO ↓ phosphorylation Akt, ERK, JNK ↓ histamine, leukotriene B4, PEG2 inhibition of ear edema induced by AA (30.5%), TPA (31.7%), and OXA (23.4%). EGCG inhibits 12.9%, 13.8%, and 5.7% of by AA, TPA, and OXA, respectively
Fucofuroeckol-A (5) 6 [39]	Eisenia bicyclis (Kjellman) Setchell 1905	1–100 μΜ	LPS-induced RAW 264.7 cells	↓ NO, PGE2, iNOS ↓ TNF-α, IL-1β, IL-6 ↓ COX-2
6,6′-Bieckol (6) 7 [44,45]	Ecklonia cava Eisenia arborea	100 and 200 μΜ 75 μΜ	LPS-induced RAW 264.7 cells ICR strain mouse	↓ NO, PGE2, iNOS ↓ TNF-α, IL-6 ↓ COX-2 inhibition of ear oedema induced by AA (41.9%), TPA (34.2%), and OXA (17.8%). EGCG inhibits 12.9%, 13.8%, and 5.7% of by AA, TPA, and OXA, respectively
6,8′-Bieckol (7) 8 [45]	Eisenia arborea	10 μΜ 75 μΜ	RBL-2H3 cells ICR strain mouse	↓ COX-2 mRNA expression inhibition of ear oedema induced by AA (39.8%), TPA (49.4%), and OXA (77.8%). EGCG inhibits 12.9%, 13.8%, and 5.7% of by AA, TPA, and OXA, respectively
8,8′-Bieckol (8) 9 [45]	Eisenia arborea	10 μΜ 75 μΜ	RBL-2H3 cells ICR strain mouse	↓ histamine, leukotriene B4, PEG2 inhibition of ear oedema induced by AA (21.0%), TPA (31.7%), and OXA (32.3%). EGCG inhibits 12.9%, 13.8%, and 5.7% of by AA, TPA, and OXA, respectively
Octaphlorethol A (9) 10 [46]	Ishige foliacea	6.2 and 12.5 μΜ	CpG-stimulated BMCD and BMDM	↓ TNF-α, IL-6, IL12 p40
Vidalol A (10) 11 [52]	Vidalia obtusiloba	n. r.	phorbol ester (PMA)—induced swelling of the mouse ear Enzymatic activity	↓ eodema (58–82%) ↓ phospholipase A2
Vidalol B (11)12 [52]	Vidalia obtusiloba	n. r.	phorbol ester (PMA)—induced swelling of the mouse ear Enzymatic activity	↓ eodema (58–82%) ↓ phospholipase A2
3-BDB (12) 13 [53,54]	Polysiphonia morrowii Polysiphonia urceolata Rhodomela confervoides	12.5, 25, 50, and 100 μM 100 mg/kg	LPS-stimulated RAW 264.7 BALB/c mice induced by DNCB	↓ IL-6, phosphorylation NF-ΚB ↓ STAT1; Tyr 701 ↓ edema inflammation, AD symptoms, Ig2
BEMB (13) 14 [56]	Polysiphonia morrowii	12.5–50 μM	LPS-stimulated RAW 264.7 and zebrafish embryos	↓ NO, iNOS, COX-2, NF-ƘB
BBDE (14) 15 [57]	Polysiphonia morrowii	0.1, 1, 2 μM	LPS-stimulated RAW 264.7	↓ NO, iNOS, COX-2, PGE2, TNF-α, IL-6, IL-1β
Compound (15) 16 [58]	Gracilaria opuntia	n. r.	Enzymatic activity	↓ COX-2, 5-LOX
Compound (16) 17 [59]	Gracilaria opuntia	n. r.	Enzymatic activity	↓ 5-LOX
Compound (17) 18 [59]	Gracilaria opuntia	n. r.	Enzymatic activity	↓ 5-LOX
Compound (18) 19 [60]	Gracilaria salicornia	n. r.	Enzymatic activity	↓ COX-2, 5-LOX
Compound (19) 20 [60]	Gracilaria salicornia	n. r.	Enzymatic activity	↓ COX-2, 5-LOX
Rutin (20) 21 [61]	Porphyra dentata	80–250 μM	LPS-stimulated RAW 264.7	↓ NO, iNOS, NF-ƘB
5β-Hydroxypalisadin B 22 (21) [64]	Laurencia snackeyi	50 μM 0.25, 0.1 and 1 µg/mL	LPS-induced RAW 264.7 LPS-induced zebrafish embryo	↓ NO, COX-2, iNOS ↓ NO, Improved survival, heart rate and yolk sac oedema size
Neorogioltriol (22)23 [66,67]	Laurencia glandulifera	8 μM 1 mg/kg	LPS-induced RAW 264.7 Writhing test in mice Formalin test in rats	↓ NO, iNOS ↓ macrophage activation induce Arginase 1, MRC1, miRNA miR-146a ↓ writhing response induced by acetic acid by 88.9% ↓ 2° phase formalin test in 48.7%
Neorogioldiol (23) 24 [67]	Laurencia sp	62.5 μM	LPS-induced RAW 264.7 C57BL/6 mice	↓ NO, iNOS ↓ macrophage activation induce Arginase 1, MRC1, miRNA miR-146a ↓ tissue damage, TNF-α, IL-6, IL-12
Compound (24) 25 [67]	Laurencia sp	10 μM	LPS-induced RAW 264.7 C57BL/6 mice	↓ NO, iNOS ↓ macrophage activation induce Arginase 1, MRC1, miRNA miR-146a ↓ tissue damage, TNF-α, IL-6, IL-12
Compound (25) 26 [68]	Gracilaria Salicornia	n. r.	Enzymatic activity	↓ 5-LOX
Fucoxanthin (26) 27 [74,77,82]	Sargassum siliquastrum (Mertens ex Turner) C.Agardh 1820	0.1–1 mg/kg 15, 30, 60 μM	LPS-induced sepsis in mice LPS-induced RAW 264.7 LPS-activated BV-2 microglia	↓ TNF-α, IL-6, IL-12, NF-ƘB ↑ rate of survival ↓ iNOS, COX-2, mRNA, TNF-α, IL-6 ↓ iNOS, COX-2, mRNA, TNF-α, IL-6 ↓ Akt, NF-Κb, ERK, p38 MAPK
Fucosterol (27) 28 [90,91,93]	Undaria pinnatifida Hizikia fusiformis (Harvey) Okamura 1932 b Panida australis c	15, 30, 60 mg/kg 1–10 µM 0.004, 0.2, 10 µM	LPS-induced ALI in mise CoCl2-induced hypoxia in keratinocytes LPS or Aβ-induced BV2 (microglial) cells	↓ lung histopathologic changes, wet-to-dry ratio ↓ TNF-α, IL-6, IL-1β, NF-κB ↓ IL-6, IL-1β, TNF-α, pPI3K and pAkt and HIF1-α accumulation ↓ L-6, IL-1β, TNF-α, NO, PGE2
Caulerpin (28) 29 [97,98]	Caulerpa racemosa (Forsskål) J.Agardh 1873 Caulerpa sertularioide	100 μmol/kg 4 mg/kg	Swiss albino mice C57BL/6 mice with colitis induced DSS	↓ formalin effects in both phases by 35.4% and 45.6%. reduction 55.8% on capsaicin-induced ear oedema model ↓ recruit cells (48.3%) on carrageenan-induced peritonitis triggering improvement of DAI and attenuating the colon shortening/ damage ↓ TNF-α, IFN-γ, IL-6, IL-17, NFκB p65 ↑ IL-10 in the colon tissue
Z-4,7,10,13,16,19-Docosahexaenoic acid-DHA (29) [102,104,106]	Sargassum natans (Linnaeus) Gaillon 1828	n. r. 3 g/day	21 volunteers (9 men and 12 postmenopausal women) with chronic inflammation and some characteristics of metabolic syndrome	RvE1 protect tissue counterregulates pro-inflammatory gene expression ↓ fumarate, pyruvate, citrate, isocitrate, malate, α-ketoglutarate ↑ succinate, glucuronate
Z-5,8,11,14,17-Eicosapentaenoic acid-EPA (30) [99,104,106]	Vertebrata lanosa (Linnaeus) T.A.Christensen 1967 Palmaria palmata (Linnaeus) F.Weber and D.Mohr 1805 Laminaria digitata (Hudson) J.V.Lamouroux 1813	n. r. 3 g/day	21 volunteers (9 men and 12 postmenopausal women) with chronic inflammation and some characteristics of metabolic syndrome	RvE1 protect tissue counterregulates pro-inflammatory gene expression ↓ fumarate, α-ketoglutarate ↑ UDP-glucuronate, glucuronate
E-9-Oxooctadec-10-enoic acid (34) [105]	Gracilaria verrucose (Hudson) Papenfuss, nom. Rejic. 1950 d	50–100 μM	LPS-induced RAW 264.7	↓ NO, TNF-α, IL-6 ↓ NF-ƘB, JAK/STAT
E-10-Oxooctadec-8-enoic acid (35) [105]	Gracilaria verrucose d	50–100 μM	LPS-induced RAW 264.7	↓ NO, TNF-α, IL-6 ↓ NF-ƘB, JAK/STAT

* The macroalgae full names are accordingly the Algaebase (https://www.algaebase.org/ (accessed on 18 December 2022)); ¹ benzene-1,3,5-triol; ² 4-(4-((6-(3,5-dihydroxyphenoxy)-4,7,9-trihydroxydibenzo[b,e][1,4]dioxin-2-yl)oxy)-3,5-dihydroxyphenoxy)dibenzo[b,e][1,4]dioxine-1,3,6,8-tetraol; ³ 4-(3,5-dihydroxyphenoxy)dibenzo[b,e][1,4]dioxine-1,3,6,8-tetraol; ⁴ 4,9-bis(3,5-dihydroxyphenoxy)benzo[b]benzo[5,6][1,4]dioxino[2,3-e]benzofuran-1,3,6,10,12-pentaol; ⁵ 4-(3,5-dihydroxy-phenoxy)benzo[b]benzo[5,6][1,4]dioxino[2,3-e]benzofuran-1,3,6,9,10,12-hexaol; ⁶ 4-(3,5-dihydroxyphenoxy)benzo[b]benzo[5,6][1,4]dioxino[2,3-e]benzofuran-1,3,6,9,10,12-hexaol; ⁷ 6,6′-bis(3,5-dihydroxyphenoxy)-[1,1′-bidibenzo[b,e][1,4]dioxin]-2,2′,4,4′,7,7′,9,9′-octaol; ⁸ 6,9′-bis(3,5-dihydroxyphenoxy)-[1,2′-bidibenzo[b,e][1,4]dioxin]-1′,2,3′,4,6′,7,8′,9-octaol; ⁹ 9,9′-bis(3,5-dihydroxyphenoxy)-[2,2′-bidibenzo[b,e][1,4]dioxin]-1,1′,3,3′,6,6′,8,8′-octaol; ¹⁰ 2-(4-(4-(4-(4-(4-(4-(3,5-dihydroxyphenoxy)-3,5-dihydroxyphenoxy)-3,5-dihydroxyphenoxy)-3,5-dihydroxyphenoxy)-2,6-dihydroxyphenoxy)-2,6-dihydroxyphenoxy)-2,6-dihydroxyphenoxy)benzene-1,3,5-triol; ¹¹ 2-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)benzene-1,3,5-triol; ¹² 2-bromo-4,6-bis(2,3-dibromo-4,5-dihydroxybenzyl)benzene-1,3,5-triol; ¹³ 3-bromo-4,5-dihydroxybenzaldehyde; ¹⁴ 3-bromo-5-(ethoxymethyl)benzene-1,2-diol; ¹⁵ bis(3-bromo-4,5-dihydroxybenzyl)ether; ¹⁶ 2-acetoxy-2-(5-acetoxy-4-methyl-2-oxotetrahydro-2H-pyran-4-yl)ethyl 4-(3-methoxy-2(methoxymethyl)-7-ethyl-3,4,4a,7,8,8a-hexahydro-2H-chromen-4-yloxy)-5-methylheptanoate; ¹⁷ 5-[7-(5-ethyl-3,4-dimethoxycyclooctyl)benzofuran-6-yl]-7-methyl-3,4,7,8-tetrahydro-2H-oxocin-2-one; ¹⁸ 2-(3-ethyl-9-(2-methoxyethoxy)-1-oxo-2,3,4,9-tetrahydro-1H-xanthen-2-yl)ethyl 5-hydroxy-9-methoxy-7,8-dimethyl-8-(5-methylfuran-2-yl)nona-3,6-dienoate; ¹⁹ 4′-[10′-[7-hydroxy-2,8-dimethyl-6-(pentyloxy)-2H-chromen-2-yl]ethyl]-3′,4′-dimethyl-cyclohexanone; ²⁰ 3′-[10′-(8-hydroxy-5-methoxy-2,6,7-trimethyl-2H-chromen2-yl)ethyl]-3′-methyl-2′-methylene cyclohexyl butyrate; ²¹ 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(((2S,4S,5S,6R)-3,4,5-trihydroxy-6-((((2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)methyl)tetrahydro-2H-pyran-2-yl)oxy)-4H-chromen-4-one; ²² (2R,5R,7S,9aS)-7-bromo-2-(bromomethyl)-3,6,6,9a-tetramethyl-2,5,5a,6,7,8,9,9a-octahydrobenzo[b]oxepin-5-ol; ²³ (1R,5S,6S)-5-(1-((3R,4S)-3-bromo-4-hydroxy-4-methylcyclohexyl)vinyl)-1,4,4-trimethyloctahydropentalene-1,6-diol; ²⁴ (1R,6S)-6-bromo-5-(1-((3R,4S)-3-bromo-4-hydroxy-4-methylcyclohexyl)vinyl)-1,4,4-trimethyloctahydropentalen-1-ol; ²⁵ O¹¹,15-cyclo-14-bromo-14,15-dihydrorogiol-3,11-diol; ²⁶ methyl 16(13→14)-abeo-7-labdebe-(12-oxo)carboxylate; ²⁷ (3R)-3-hydroxy-4-((3E,5E,7E,9E,11E,13E,15E)-18-((1S,4S,6R)-4-hydroxy-2,2,6-trimethyl-7-oxabicyclo[4.1.0]heptan-1-yl)-3,7,12,16-tetramethyl-17-oxooctadeca-1,3,5,7,9,11,13,15-octaen-1-ylidene)-3,5,5-trimethylcyclohexyl acetate; ²⁸ (3S,10R,13R,17R)-17-((2R)-5-hydroxy-5-isopropylhept-6-en-2-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol; ²⁹ dimethyl(6E,13E)-5,12-dihydrocycloocta[1,2-b:5,6-b’]diindole-6,13-dicarboxylate; ^a Current accepted name Ecklonia cava subsp. stolonifera (Okamura), S. Akita, K. Hashimoto, T. Hanyuda and H. Kawai, 2020; ^b Current accepted name Sargassum fusiforme (Harvey) Setchell 1931; ^c Unknown name, others authors indicate Posidonia australis Hooker F., 1858; ^d Current accepted name Gracilaripsis longissimi (S. G. Gmelin) Steentoft, L. M. Irvine and Farnham, 1995; n. r. = non revealed.