Table 1.

Studies on the anti-inflammatory activity of Sargassum crude extracts and their partitions.

Sample	Observed Response	Tested Compound	Model	Ref.
Subgenus Sargassum
S. binderi	(1)Decreased serum interleukin (IL)-2, tumor necrosis factor (TNF)-α, and IL-1β production, improve wound healing rate, and elevated serum IL-4 1 (2)Decreased nitric oxide (NO) production 2,3	Phyto-oleic acid nanovesicles (PONVs) made by petroleum ether extract 1; water extract 2; and ethanolic precipitate of water extract 3	Wounded streptozotocin-induced diabetic rats 1; and lipopolysaccharide (LPS)-induced RAW 264.7 2,3	1 [34] * 2 [35] * 3 [36] *
S. patens	(3)Decreased NO, prostaglandin E2 (PGE2), IL-6, TNF-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 production 1,2 (4)Inhibition of p65 nuclear factor kappa B (NF-kB) translocation 1 (5)Decreased ear edema volume and mastocyte infiltration 1	Ethanol extract 1,2	LPS-induced RAW 264.7 1,2; and croton oil-induced rat ear edema 1	1 [37] 2 [38]
S. wightii	(1)Significant inhibition of 5-lipoxygenase (LOX), COX-1, and COX-2 in vitro 1 (2)Inhibition of in vitro albumin denaturation 2,6 (3)Decreased paw edema volume 3,4,5 (4)Inhibition of red blood cells (RBC) hemolysis and proteinase activity 6	Methanol-ethyl acetate extract 1; chloroform extract 1,3; ethanol extract 2,3; hexane extract 3, 6; methanol extract 4,5,6; butanol extract 4; and ethyl-acetate extract 6	In vitro inhibition of 5-LOX, COX-1, and COX-2 1; albumin denaturation inhibition 2,6; carrageenan-induced rat paw edema 3,4,5; and RBC membrane stabilization and proteinase inhibition 6	1 [39] * 2 [40] * 3 [41] * 4 [23] 5 [42] * 6 [43] *
S. swartzii	(1)Decreased serum TNF-α, IL-6, and C-reactive protein (CRP) production in diabetic rats 1 (2)Decreased paw edema volume and inflammatory exudate 2 (3)Reduction of inflammatory cells accumulation, cell swelling, and dilated sinusoids in hepatocytes through histopathological observation 3 (4)Decreased NO production 4	Gold nanoparticles of water extract 1; methanol extract 2; water extract 3; and diethyl ether fraction of methanol extract 4	Alloxan-induced diabetic Wistar rats 1; carrageenan-induced rat paw edema and peritonitis 2; acetaminophen-induced hepatotoxicity in mice 3; and LPS-induced RAW 264.7 4	1 [44] * 2 [45] * 3 [46] 4 [47] *
S. crassifolium	Decreased rat paw edema volume	β-glucan extract yielded from acid and ultrasound methods	Carrageenan-induced rat (Rattus novergicus) paw edema	[48] *
S. ilicifolium	Decreased paw edema volume	Methanol extract;	Carrageenan-induced rat paw edema	[49] *
S. duplicatum	Decreased NO production 1,2	Water extract 1; and ethanolic precipitate of water extract 2	LPS-induced RAW 264.7 1,2	1 [35] * 2 [36] *
S. subrepandum	Improved plasma lipid profile (plasma cholesterol, triglycerides, low density lipoprotein/LDL, and high density lipoprotein/HDL), decreased serum malondialdehyde (MDA), NO, TNF-α, and leptin production, and increased serum adiponectin level	Methanol extract (100 mg/kg)	Atherogenic diet-induced female Sprague Dawley rats	[50]
S. polycystum	(1)Decreased rat paw edema volume 1 (2)Decreased serum TNF-α and intact condition of hepatocytes 2 (3)Improvement of inflammatory condition in histopathological evaluation of liver and kidney tissue 3 (4)Decreased production of NO and proinflammatory cytokines (TNF-α, IL-1β, and IL-6) 4	Hexane fraction from methanol extract 1; ethanol extract 2,3; water extract 3; hexane, dichloromethane, and methanol extract 4	Carrageenan-induced rat paw edema 1; acetaminophen-induced hepatoxicity in rat 2; high calorie diet and low dose streptozotocin-induced type II diabetes 3; and LPS-induced C8B4 microglia cells 4	1 [51] * 2 [52] * 3 [53] * 4 [54] *
S. vulgare	(1)Decreased rat paw edema volume 1 (2)Inhibition of COX-1 and COX-2 activity 2	Methanol extract 1; ethyl acetate extract 2	Carrageenan-induced rat paw edema 1; and in vitro inhibition to COX-1 and COX-2 enzymes 2	1 [55] 2 [56]
Subgenus Bactrophycus
S. thunbergii	(1)Decreased production of NO, TNF-α 1,2,4, IL-1β, and IL-6 1,2 (2)Decreased ear edema volume 3 (3)Suppression of iNOS expression 4 (4)Decreased NO production and increased reactive oxygen species (ROS) scavenging activity 5 (5)Suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression 6 (6)Suppression of ear edema and erythema 7 (7)Decreased production of myeloperoxidase (MPO) and enhanced production of antioxidant enzymes (superoxide dismutase (SOD)-1 and glutathion reductase) 8	Ethanolic extract of fermented samples and its fractions 1; ethyl acetate extract 2; extract of dichloromethane, ethanol, and water 3; ethanol 70% extract 4; ethanol extract 5; and methanol extract 6,7,8	LPS-induced RAW 264.7 1,2,5; rat ear edema 3; LPS-induced BV-2 microglial cells 4; H2O2-induced RAW 264.7 5; phorbol 12-myristate 13 acetate (PMA)-induced HT1080 6; PMA-induced mouse ear edema and erythema 7; and TNF-α stimulated human monocytic leukemia 8	1 [18] 2 [57] 3 [22] 4 [58] 5 [59] 6 [60] 7 [61] 8 [62]
S. fulvellum	(1)Decreased production of COX-2, iNOS, pro-inflammatory cytokines, NO, and PGE2 1,2,3 (2)Increased expression of CU/Zn- superoxide dismutase (SOD) and reduced ROS production 1 (3)Decreased ear edema volume 4 (4)Suppressed NO production 5,6 and reduced cytoplasmic activity 5, (5)Decreased serum IL-4, immunoglobulin E (IgE), and TNF-α production, and reduction of IL-4, IL-5, and IL-13 in mice splenocytes 7 (6)Suppression of ear edema and erythema formation 8	Ethyl acetate fraction from ethanol extract 1, hexane fraction 2; ethanol extract 3,4,7; dichloromethane extract 4; and water extract 4,5; ethanol precipitate of water extract 6; and methanol extract 8	Ultraviolet B (UVB)-induced HaCaT keratinocytes and BALB/c mice 1; LPS-induced RAW 264.7 2,3,5, 6; rat ear edema 3,4; dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in BALB/c mice 7; and PMA-induced mouse ear edema and erythema 8	1 [24] 2 [63] 3 [64] 4 [22] 5 [35] * 6 [36] * 7 [65] 8 [61]
S. serratifolium	(1)Decreased NO, PGE2, iNOS, and COX-2 production 1,2,4 (2)Inhibition of inhibitor kappa B (IkB) degradation 1,3 (3)Decreased expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, monocyte chemoattractant protein (MCP)-1, keratinocyte chemoattractant (KC) 3,6, and MMP-9 6, and elevated heme oxygenase 1 expression 3 (4)Inhibition of NF-kB transactivation 3,4,6, MAPKs phosphorylation, and phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) activation 4 (5)Decreased expression of MMP-1, MMP-3, and MMP-13 4 (6)Decreased macrophage infiltration and MCP-1 expression in epididymal tissue 5	Ethanol extract 1,2,4; hexane fraction from ethanolic extract 3; meroterpenoid-rich extract from hexane fraction 5,6	LPS-induced mouse peritoneal macrophage 1; LPS-induced BV-2 microglial cells and LPS-induced rat hippocampus cells 2; TNF-α-induced human umbilical vein endothelial cells (HUVECs) 3,6; IL-1β-treated SW1353 human chondrocytes 4; high fat (HF)-fed C57BL/6J mice 5; and high cholesterol diet (HCD)-fed C57BL/6J mice 6	1 [66] 2 [67] 3 [20] 4 [68] 5 [28] 6 [29]
S. miyabei	(1)Suppressed NO, IL-6, TNF-α, IL-1β, iNOS, and COX-2 production (2)Decreased mitogen-activated protein kinases (MAPKs) and NF-kB activation (3)Decreased ear edema volume	Ethanol extract	LPS-induced RAW 264.7 and rat ear edema	[69]
S. fusiforme	(1)Suppressed ear edema formation and RBL (rat basophilic leukemia) degranulation 1 (2)Decreased activity of phospholipase A2 (PLA2), COX-2, LOX, and hyaluronidase 1 (3)Decreased NO 2,4 and ROS 4 production (4)Decreased TNF-α production, and elevated production of IL-6 and IL-10 production 3 (5)Decreased NO, iNOS, COX-2, and pro-inflammatory cytokines production via inhibition of MAPKs activation 5 (6)Suppression of ear edema and erythema formation 6	Administration of diethyl ether fraction percutaneously and orally 1; ethyl acetate fraction from ethanol 30% extract 2; water extract 3; methanol extract and its fractions (dichloromethane, ethyl acetate, n-butanol, water) 4; ethanol extract of fermented and non-fermented sample 5; and methanol extract 6	Rat ear edema and RBL cells 1, LPS-induced RAW 264.7 2,4,5; tert-butyl hydroperoxide (t-BHP)-induced RAW 264.7 RAW 264.7 4; LPS-induced C2C12 myotube cells 3; and PMA-induced mouse ear edema and erythema 6	1 [31] 2 [70] 3 [71] 4 [33] 5 [72] 6 [61]
S. horneri	(1)Decreased production of NO 1,2,4,6,7,8,9, PGE2 2,4,6,7,9, and pro-inflammatory enzymes (iNOS and COX-2) 1,4,6,7,9 (2)Inhibition of extracellular signal-regulated kinase (ERK) 1,4,6,9, c-Jun-N-terminal kinase (JNK) 4,6,9, p38 1,6,9, and NF-κB 1,4,6,9 activation (3)Hindered cell migration and decreased MMP-2 and MMP-9 activity 3 (4)Decreased population of T helper, T cytotoxic, granulocytes, eosinophil, and monocytes 5 (5)Decreased production of TNF-α 5,6,7 IL-1β 5,6,7, IL-6 5,6,7, IL-4 5, IL-5 5, and IL-13 5 (6)Elevated expression of hemeoxygenase 1 8 (7)Decreased NO production and increased ROS scavenging activity 10 (8)Suppression of ear edema and erythema formation 11	Ethanol 70% extract 1,4,5; ethanol 85% extract 2; ethanol extract 3,6,7,10 and its fraction 3,6; methanol 80% extract and its fraction 8; combination of Ecklonia cava and S. horneri ethanol 70% extracts 9; and methanol extract 11	LPS-induced RAW 264.7 1,2,4,6,8,9,10; PMA-induced HT1080 fibrosarcoma 3; concanavalin A-induced rat splenocytes 5; fine dust (FD)-induced RAW 264.7 7; and PMA-induced mouse ear edema and erythema 11	1 [73] 2 [74] 3 [30] 4 [75] 5 [76] 6 [19] 7 [77] 8 [78] 9 [79] 10 [59] 11 [61]
S. coreanum	(1)Decreased production of NO, IL-6, TNF-α, IL-1β, iNOS, and COX-2 via inhibition of NF-kB activation (2)Decreased ear edema volume	Ethanol extract	LPS-induced RAW 264.7 and rat ear edema	[80]
S. ringgoldianum	Suppression of mouse ear edema and erythema formation	Methanol extract	PMA-induced mouse ear edema and erythema	[61]
S. micracanthum	(1)Decreased production of NO, IL-6, TNF-α, IL-1β, iNOS, and COX-2 1 (2)Inhibition of NF-kB activation 1 (3)Decreased ear edema volume 2	Water extract 1; and ethanol extract 2	LPS-induced RAW 264.7 1; and croton oil-induced rat ear edema 2	1 [81] 2 [82]
S. macrocarpum	(1)Decreased production of IL-12 p40, IL-6, and TNF-α (2)Inhibition of NF-kB nuclear translocation and IkB degradation 1,2 (3)Decreased production of NO, PGE2, iNOS, COX-2, TNF-α, and IL-1β 2 (4)Suppression of PI3K/Akt and ERK phosphorylation and increased nuclear factor erythroid-2-related factor 2 (Nrf2) and hemeoxygenase-1 expression 2	Ethanol 70% extract 1,2	CpG-DNA-induced bone marrow-derived macrophages (BMDMs) and bone marrow-derived dendritic cells (BMDCs) from C57BL/6 mice 1; and LPS-induced RAW 264.7 2	1 [83] 2 [84]
S. sagamianum	(1)Decreased production of NO, IL-6, IL-1β, TNF-α, iNOS, and COX -2 via inhibition of NF-kB p65 activation 1 (2)Decreased ear edema volume 1 (3)Suppression of mouse ear edema and erythema formation 2	Ethanol extract 1; and methanol extract 2	LPS-induced RAW 264.7 and rat ear edema 1; and PMA-induced mouse ear edema and erythema 2	1 [85] 2 [61]
S. muticum	(1)Decreased NO and PGE2 production, iNOS and COX-2 expression (protein and mRNA), IL-1β and IL-6 expression (mRNA) 1 (2)Decreased production of IL-6, TNF-α, and interferon (IFN)-γ in serum and lymphocyte 2 (3)Improved arthritis score, edema condition, and histology of the knee joint 2 (4)Suppressed MMP-1 expression via inhibition of activator protein (AP)-1 activation and its binding to MMP-1 promoter 3 (5)Decreased production of serum IL-2, TNF-α, and IL-1β 4 (6)Suppression of p38 and JNK phosphorylation 5	Ethanol 80% extract and its fraction (hexane, CH2Cl2, EtOAc, BuOH, and water) 1; ethanol 70% extract 2; ethyl acetate fraction of ethanol extract 3,5; and methanol extract 4	LPS-induced RAW 264.7 1; Collagen-induced arthritis DBA/1J mice 2; UVB-induced HaCaT keratinocytes 3,5; and STZ-induced hepatic injury in Wistar rats 4	1 [21] 2 [27] 3 [86] 4 [87] 5 [88]
S. hemiphyllum	(1)Decreased production of histamine and β-hexosaminidase in PMA-induced rat peritoneal mastocyte 1 (2)Decreased production of IL-8 and TNF-α in A23187-induced HMC-1 1 (3)Inhibition of NF-kB activation in TNF-α-induced 293T cells 1 (4)Decreased iNOS expression via inhibition of MAPKs activation 2 (5)Decreased NO production and increased ROS scavenging activity 3	Methanol extract 1,2; and ethanol extract 3	PMA-induced rat peritoneal mastocyte, A23187-induced HMC-1/human mast cell, and TNF-α-induced 293T cells 1; β-amyloid protein (Aβ)-induced HT-22 mouse neuronal cells 2; and LPS and H2O2-induced RAW 264.7 3	1 [89] 2 [90] 3 [59]
S. confusum	(1)Decreased iNOS expression via inhibition of MAPKs activation 1 (2)Suppression of mouse ear edema and erythema formation 2	Methanol extract 1,2	β-amyloid protein (Aβ)-induced HT-22 mouse neuronal cells 1; and PMA-induced mouse ear edema and erythema 2	1 [90] 2 [61]
S. siliquastrum	Suppression of NO and iNOS production	Aqueous extract of sample fermented by Lactobacillus sp. SH-1	LPS-induced RAW 264.7	[91]
S. pallidum	(1)Enhanced production of serum IL-2, IL-4, and IL-10 (2)Decreased production of serum IL-6, IL-1β, and TNF-α	Water extract	N-methyl-N′-nitro-nitrosoguanidine (MNNG)-induced gastric cancer rats	[92]

Note: References followed by an asterisk (*) used samples from a tropical area. The superscripted numbering of reference, model, tested compund, and observed response in the same row are related to one another. This superscripted numbering is discontinous between rows and only applied to the same row.