Table A4.
Effects of oral supplementation of brown seaweed derived phenolic compounds on inflammation-related parameters.
| Compound/Format | Effective Concentrations | Algal Source | Experimental Model | Inflammatory Phase 1 | Significant Findings 2 | Reference |
|---|---|---|---|---|---|---|
| (poly)phenol-rich seaweed extract | 400 mg; 8 weeks | Ascophyllum nodosum | 80 participants; 30–65 years old with a body mass index (in kg/m2) ≥ 25. |
Steady state | ↓ DNA damage in obese people No significant differences in CRP, antioxidant status and inflammatory cytokines |
[7] |
| MeOH–EtAc extract => phlorotannin | 100–200 mg/kg/day 3 days before experiment |
Eisenia bicyclis = Ecklonia bicyclis | Sprague Dawley rat, platelet aggregation + activation | Steady state | Eisenia bicyclis extract strongly inhibits in vivo platelet aggregation. Mechanism in vitro: downregulated ADP-induced platelet activation (Ca-mobilization, fibrinogen binding, granule release—mediated via decreased Src, PI3K, PLCgamma2, MAPK signaling) |
[122] |
| MeOH extract=> Eckol | 25, 50, 100 μg/mL, pretreatment 2 h prior to anaphylaxis induction 25, 50, 100 μg/mL, 24 h |
Ecklonia cava | BALB/c mice; anti-DNP-IgE induced PCA C57BL/6 male mice; anti-DNP-IgE and IgE-BSA induced allergic |
allergy | ↑ binding of IgE to FcɛRI ↓ FcɛRI expression ↓ mRNA level of IL-1β, IL-6, TNF-α, IFN-γ ↓ NF-κB nuclear translocation ↓ IκB degradation ↓ secretion of inflammatory mediators, such as histamine, β-hexosaminidase, leukotrienes and prostaglandins ↓ production of Th2-type cytokines, such as IL-4, IL-5, IL-13 (not 25 ug/mL) |
[123] |
| MeOH-ethyl acetate extract (crude (72–74%) phlorotannins = phloroglucinol oligomer); | oral 1× or 2×; 0.1, 1 mg/ear |
Ecklonia kurome
Ecklonia arborea |
male ICR mouse; AA induced ear oedema |
allergy | inhibitory effects are comparable to known anti-allergic agents presumed mechanisms: inhibition of MC degranulation + inhibition of COX-2 and LOX, and to lesser extent PLA2, activities |
[125] |
| (poly)phenol-rich brown algae extract | 100 mg/kg 500 mg/kg; 12 weeks |
Ecklonia cava | C57BL/6 male mice; HFD+/− seaweed supplement | 1,3 | ↓ MCP1 ↓ TNF-α ↓ IL-1 ↓ COX-2 (slightly decreased) protein level ↓ NF-κB protein level↓ Body weight ↓ adipose tissue weight ↓ deposition in the liver ↓ TG and TC levels ↓ leptin and adiponectin ratio ↓ Glucose Tolerance Test ↓ Insulin Resistance ↑ protein levels of P-AMPK ↑ SIRT1 protein levels ↑ PGC1α protein levels in the nucleus |
[128] |
| A single compound Pyrogallol-Phloroglucinol-6,6-Bieckol from the brown algae ethanoic extract | 2 mg/kg; 4 weeks |
Ecklonia cava | C57Bl/6N mice; HFD +/− seaweed supplement |
1,2,3 | In visceral fat: ↓ TNF-a mRNA levels ↓ IL-1β mRNA levels ↓ Macrophage infiltration ↓ M1/M2 ratio (CD86 and CD80 lower, CD163 and CD206 higher) ↓ RAGE ↓ RAGE-RAGE Ligand Bonding ↓ Body weight ↓ size of visceral adipocytes ↓ fat mass ↓ serum TG and TC ↓ AGEs, HMGB1 and S100beta secret by adipocytes |
[137] |
| Polyphenols-rich Ethanol extract | 200, 400 mg/kg; 7 days |
Sargassum horneri | BALB/c female mice; PM induced airway inflammation in allergic asthma |
1,2 | ↓ granulocyte infiltration ↓ macrophage infiltration ↓ TLRs expression in lungs ↓ NF-κB pathway activation ↓ pro-inflammatory cytokines IL-1β, TNF-α, IL-6 expression in lung↑ IL-10 expression in lung ↓ IL-25, IL-33, IL-8, TGF-β in lung ↓ cytokines (IL-25, IL-33) in serum |
[124] |
| phlorotannins-rich extract | PREC (75 and 150) or dieckol (50 and 100 mg/kg; 4 weeks Combination cisplatin (1, 3 or 5 μM) with PREC (35, 50, 75 or 100 μg/mL); 48 h |
Ecklonia cava | BALB/c athymic female nude mice; SKOV3 cells induced ovarian carcinoma | 1 | PREC: ↓ Akt in ovarian cancer ↓ NF-κB in ovarian cancer ↑ intracellular ROS in ovarian cancer ↓ cisplatin-induced ROS in normal HEK293 ↑ ROS production in SKOV3 cells the combined treatment of PREC and cisplatin: ↓ ROS production in in SKOV3 cells and normal HEK 293cells Dieckol: ↑pathwayscisplatin-induced ROS production Dieckol: ↓pathwayscisplatin-induced ROS production (slightly) |
[129] |
| phlorotannin derived from the brown alga | 0.5 and 1.0 mg/kg/day; Pretreatment for 7 days |
Ecklonia stolonifera | Male Kunming mice; CCl4 induced acute liver injury |
1,2 | ↓ TNF-a ↓ IL-1β ↓ IL-6 ↓ ROS ↑ IL-10 ↑ CD11c+ |
[135] |
| Ethyl acetate fraction containing diphlorethohydroxycarmalol | 6.25, 12.5, 25 μg/mL | Ishige okamurae | zebrafish embryo; FD induced ROS, NO production and cell death |
1,2 | ↓ ROS production ↓ NO production |
[134] |
| polyphenol-rich brown algae extract | 25, 50 and 100 μg/mL; pretreatment for 1 h | Ecklonia cava | Zebrafish embryos | 1,2 | ↓ ROS expression ↓ NO expression ↓ iNOS |
[133] |
| chloroform–methanol extract Apo-9′-fucoxanthinone (AF) |
25, 50 and 100 μg/mL; pretreatment for 1 h | Sargassum muticum | Zebrafish embryos | 1,2 | ↓ IL-1β, ↓ TNF-α ↓ ROS ↓ COX-2 ↓ NF-κB ↓ MAPK ↓ iNOS ↓ NO |
[131] |
| Six purified phlorotannins ((eckol; 6,60-bieckol; 6,80-bieckol; 8,80-bieckol; phlorofucofuroeckol (PFF)-A and PFF-B) |
10, 100, 200 µM | Eisenia arborea | ICR mice; AA, TPA and OXA induced ear swelling |
1 | ↓ COX-2 mRNA expression ↓ COX-2 enzymatic activity |
[136] |
| Ethanol extract including Dieckol, 2,7-phloroglucinol-6,6-bieckol (PHB), PFF-A and pyrogallol-phloroglucinol-6,6′-bieckol (PPB) | 2.5 mg/kg; 4 weeks |
Ecklonia cava | 57BL/6N mice; HFD+/− seaweed supplement | 1,2,3 | ↓ TNF-α ↓ IL-6 ↓ TLR4 expression ↓ NF-kB expression ↓ CD11b ↓ CD86 ↑ CD206 ↓ body weight ↓ food intake ↓ fat mass ↓ leptin resistance ↑ leptin sensitivity ↓ PPAR expression ↓ CEBP expression ↓ FAS expression ↓ ACC expression ↓ ER |
[126] |
| Ethanolic extract including phlorotannin | 70 mg/kg; 4 weeks |
Ecklonia cava | male 57BL/6N mice, HFD+/− seaweed supplement | 1,2,3 | ↓ NF-kB ↓ TNF-α ↓ IL-6 ↓ TLR4 expression ↓ CD4 and CD8a ↓ CD11b ↑ CD206 ↓ CD80 ↑ IL-10 ↑ TGF-β mRNA ↓ Body weight ↓ Food intake ↓ Adipocyte size ↓ Leptin resistance ↓ RAGE |
[127] |
| phlorotannins-rich ethanolic extract | 100, 200, 400 mg/kg/day; 8 weeks |
Ecklonia cava | Male Sprague Dawley rats; Experimental periodontitis induced by placing a sterile 4-0 silk ligature around the gingival cervix of the right mandibular second molar teeth |
1,2 | ↓ COX-2 activity ↓ PGE2 ↓ NO ↓ iNOS |
[130] |
| Ethanolic extract and PPB | ECE: 70 mg/kg PPB: 2.5 mg/kg; 4 weeks |
Ecklonia cava | Male C57BL/6N mice; HFD+/− seaweed supplement | 1,2,3 | ↓ MCP-1 ↓ TNF-α ↓ IL-6 ↓ IL-10 ↓ iNOS ↓ CD80 ↑ CD206 ↓ ER stress ↓ size of white adipocytes ↑ PPAR expression |
[138] |
| baicalein, luteolin, rosmarinic acid and cis-2-decenoic acid (10-HAD) |
Test diet for mice:(baicalein (650 mg/kg diet), luteolin (300 mg/kg diet), rosmarinic acid (500 mg/kg diet), monolaurin (500 mg/kg diet), 10-HAD (500 mg/kg diet)); 4 weeks Capsule for human: (baicalein 250 mg/day, luteolin 75 mg/day, rosmarinic acid 100 mg/day, monolaurin 250 mg/day, 10-HAD 100 mg/day and iodine 0.15 mg/day); 3 times/day 6 months |
Unknown | C3H/HeN inbred female mice; LD infection +/− test diet Adult human; with a history of acute LD |
1,2 | Animal study: ↓ IL-6 ↓ TNF-α ↓ INF-γ Human study: By administration of the composition, 17.7% had slight physical and psychological improvement, and 17.7% were none responsive ↓ IL-17 |
[139] |
| commercial (30%) polyphenolic fraction (VNP)oral admin |
Rat: 1 dose 2000 mg/kg Human: 2400 mg/day 8 weeks |
Sargassum fusiformi, Ecklonia kurome, Ecklonia Stolonifera, Eisenia bicyclis and Ecklonia cava | Sprague Dawley rat human (men) |
1 | rat: serum ferric reducing antioxidant power (FRAP) significantly elevated 30 min after treatment, but declined quickly thereafterhuman: ↑ erectile function (significantly) =usefulness of these polyphenolic compounds as chemo preventive agents against vascular risk factors originating from oxidative stress |
[132] |
| Compound 21 | 35 mg/kg; 7 days |
Synthesized by the department of pharmaceutical chemistry | Female Lewis rats; MBP-induced EAE |
3 | Attenuates neurological deficits, immune infiltration and demyelination in EAE rats Reduces the population of Th1/Th17 cells and inhibits their infiltration into the CNS |
[142] |
| phloroglucinol derivative Compound 21 |
1, 5, 10, 20, 50 mg/kg; 4 weeks |
Unknown | Cuprizone induced intoxication in mice, | 3 | significantly improved neurological dysfunction and motor coordination impairment decreased microglia and astrocytes activities and the subsequent neuro-inflammatory response |
[141] |
| EtOAc Fraction of seaweed Crude Extract | 200 mg/kg; 8 weeks |
Ecklonia cava from Jeju or Gijang | C57BL/6 mice; HFD+/− seaweed supplement | 1,3 | ↓ TNF-a mRNA levels ↓ IL-1ß mRNA levels↓ body weights ↓ weight gain ↓ fat tissue mass ↓ Plasma ALT and cholesterol levels ↑ PPARγ2 mRNA expression ↑ C/EBPα, mRNA ↓ Blood glucose levels |
[140] |
1 Phases of inflammation as indicated in Table 1: 1-initiation of inflammation; 2-short term amplification and regulation; 3-short- or long-term consequences; 2 Symbols used: ↑—increase; ↓—decrease; =—no change.