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. 2021 Jun 25;10(7):1478. doi: 10.3390/foods10071478

Table 2.

Selected in vivo or ex vivo studies of the anti-inflammatory activity of phlorotannins extracts and isolated phlorotannins from brown algae.

Extract/Compound Model Conditions Effect Ref.
Cystoseira sedoides
EtOH 50% → Fract. PE → DCM → EtOAc Model 1—XYL-induced mice ear edema
Models 2—Carrageenan-induced paw edema in Wistar rats
Model 1—50 and 100 mg EtOAc/kg s.c. 30 min prior to XYL application
Model 2—50 and 100 mg EtOAc/kg i.p. 30 min prior to carrageenan application
Model 1—↓ swelling up to 83%
Model 2—↓ swelling up to 81%
[98]
Cladostephus spongiosis
EtOH 50% → Fract. PE → DCM → EtOAc Model 1—XYL-induced mice ear edema
Models 2—Carrageenan-induced paw edema in Wistar rats
Model 1—50 and 100 mg EtOAc/kg s.c. 30 min prior to XYL
Model 2—50 and 100 mg EtOAc/kg i.p. 30 min prior to carrageenan
Model 1—↓ swelling up to 69%
Model 2—↓ swelling up to 71%
[98]
Padina pavonica
EtOH 50% → Fract. PE → DCM → EtOAc Carrageenan-induced paw edema in Wistar rats 50 and 100 mg EtOAc/kg i.p. 30 min prior to carrageenan ↓ swelling up to 58% [98]
Sargassum horneri
EtOH 70% OVA + PM-induced lung inflammation in BALB/c mice 200 and 400 mg extract/kg orally administered before PM ↓ iNOS and COX-2, IL-1β, IL-6, TNF-α, pERK 1/2, p-p38-MAPK and p-JNK; ↑ HO-1 and Nrf-2 [99]
Sargassum sagamianum
EtOH 80% Ear edema in ICR mice 0–100 µg/mL of extract + 1 μg/mL LPS ↓ swelling [92]
Sargassum fulvellum
EtOH 95% → fract H2O → EtOAc → n-But UVB-induced BALB/c mice 3 and 10 μg topically applied in the back 30 min prior to irradiation EtOAc fraction ↓ NO, PGE2, TNF-α, COX-2 and iNOS [94]
Myagropsis myagroides
EtOH 96% PMA-induced ear edema in mice 90 µg topically administered 1 h prior to PMA injection ↓ swelling in 67% [100]
Ecklonia cava
EtOH 70% Periodontitis-induced Sprague-Dawley rats 100–400 µg extract/kg/day for 8 weeks ↓ gene expression IL-1β, MMP-2 and -9 and RANKL/OPG ratio [83]
EtOH 30% → EtOH 95% LPS-induced septic shock in C57BL/6 mice 10–100 mg/kg/d orally administered over 7 days before i.p. of LPS (25 mg/kg) ↓ NO, PGE2, iNOS, COX-2, IL-6, TNF-α, HMGB-1, and p-NIK, p-TAK1, p-IKK, p-IκB α, NF-κB-p50 and -p65; ↑ HO-1 and Nrf-2 [101]
Ascophyllum nodosum
EtOH 60% → fract → food-grade capsule (101·89 mg TPC) LPS-induced Human blood ex vivo Oral administration of a single capsule prior to blood collection ↓ IL-6 [102]
Isolated compounds
6,6′-Bieckol from Eisenia arborea AA, TPA, OXA-induced ear edema in ICR mice Topical application (15 nmol/µL) with each sensitizer ↓ swelling in 62%, 36% and 59%, respectively [103]
AA, TPA, OXA-induced ear edema Oral gavage of 75 nmol, 18 h prior to each sensitizer ↓ swelling 42%, 34% and 18%, respectively [104]
6,6′-bieckol from Myagropsis myagroides PMA-induced ear edema in mice 30 µg topically administered, 1 h prior to PMA injection ↓ swelling in 64% [100]
6,8′-bieckol from Eisenia arborea AA, TPA, OXA-induced ear edema in ICR mice Topical application (15 nmol/µL) with each sensitizer ↓ swelling in 56%, 66% and 78%, respectively [103]
AA, TPA, OXA-induced ear edema Oral gavage of 75 nmol, 18 h prior to each sensitizer ↓ swelling 40%, 49% and 78%, respectively [104]
8,8′-Bieckol from Eisenia arborea AA, TPA, OXA-induced ear edema in ICR mice Topical application (0.01–0.1 mg/mL) with each sensitizer ↓ swelling up to 80%, 49% and 71%, respectively [105]
AA, TPA, OXA-induced ear edema Oral gavage of 75 nmol, 18 h prior to each sensitizer ↓ swelling 21%, 32% and 32%, respectively [104]
Dieckol from Eisenia bicyclis Acetic acid-induced ICR mice 20 µM, 6 h prior to i.p. 0.7% acetic acid ↓ CAMs and adhesion and migration of leucocytes [79]
Dieckol from Ecklonia cava γ-radiation induced hepatocytes from Wistar rats 5–20 µM 1 h prior to irradiation (8 Gy/min) ↓ NF-kB and COX-2 [65]
CoCl2-induced hepatocytes from ICR mice 100 µM 30 min prior to CoCl2 stimulation (500 µM) ↓ COX-2 and p-p38-MAPK [106]
High glucose-induced zebrafish 20 µM 16 h prior to glucose ↓ NO, iNOS and COX-2 [35]
UVB-irradiated zebrafish embryos 50 µM 1 h prior to irradiation (50 mJ/cm2) ↓ NO [107]
Eckol comercial CCl4-injured livers of Kunming mice 0.5 and 1.0 mg compound/kg/day orally administered over 7 days before i.p. 0.5% CCl4 ↓ IL-1β, IL-6 and TNF-α, ↑ IL-10 [67]
Eckol from Ecklonia cava UVB-irradiated zebrafish embryos 50 µM 1 h prior to irradiation (50 mJ/cm2) ↓ NO [107]
Eckol from Eisenia arborea AA, TPA, OXA-induced ear edema in ICR mice Topical application (0.01–0.1 mg/mL) with each sensitizer ↓ swelling up to 49%, 38% and 65%, respectively [105]
AA, TPA, OXA-induced ear edema Oral gavage of 75 nmol, 18 h prior to each sensitizer ↓ swelling 13%, 40% and 19%, respectively [104]
Eckol from Eisenia bicyclis Acetic acid-induced ICR mice 20 µM, 6 h prior to i.p. 0.7% acetic acid ↓ CAMs and adhesion and migration of leucocytes [79]
Eckstolonol from Ecklonia cava UVB-irradiated zebrafish embryos 50 µM 1 h prior to irradiation (50 mJ/cm2) ↓ NO [107]
Phlorofucofuroeckol-A from Eisenia arborea AA, TPA, OXA-induced ear edema in ICR mice Topical application (0.01–0.1 mg/mL) with each sensitizer ↓ swelling up to 68%, 44% and 77%, respectively [105]
Pholorofucofuroeckol-A from Eisenia bicyclis AA, TPA, OXA-induced ear edema Oral gavage of 75 nmol, 18 h prior to each sensitizer ↓ swelling 31%, 32% and 23%, respectively [104]
Phlorofucofuroeckol-B from Eisenia arborea AA, TPA, OXA-induced ear edema in ICR mice Topical application (0.01–0.1 mg/mL) with each sensitizer ↓ swelling up to 78%, 56% and 72%, respectively [105]
AA, TPA, OXA-induced ear edema Oral gavage of 75 nmol, 18 h prior to each sensitizer ↓ swelling 42%, 38% and 41%, respectively [104]
Phloroglucinol commercial Acetic acid-induced ICR mice 20 µM, 6 h prior to i.p. 0.7% acetic acid ↓ CAMs and adhesion and migration of leucocytes [79]
Phloroglucinol from Ecklonia cava UVB-irradiated zebrafish embryos 50 µM 1 h prior to irradiation (50 mJ/cm2) ↓ NO [107]
Triphlorethol A from Ecklonia cava UVB-irradiated zebrafish embryos 50 µM, 1 h prior to irradiation (50 mJ/cm2) ↓ NO [107]

↓—decrease; ↑—increase; DCM—dichloromethane; Ac—acetone; EtOH—ethanol; EtOAc—ethyl acetate; n-But—n-buthanol; PE—petroleum ether; LPS—lipopolysaccharide; AA—arachidonic acid; TPA—12-O-tetradecanoylphorbol-13-acetate; OXA—oxazolone; OVA—ovalbumin; PMA—phorbol 12-myristate 13-acetate; HMGB1—high mobility group protein 1; CAMs—cell adhesion molecules; PGE2—prostaglandin E2; TNF-α—tumor necrosis factor α; IL-6—interleukin 6; IL-1β—interleukin 1β; IL-10—interleukin 10NO—nitric oxide; COX-2—cyclooxygenase-2; iNOS—inducible nitric oxide synthase; MMP—matrix metalloproteinase; p-IKKα/β—phospho-IkB kinase; p-IkBα—phospho nuclear factor kB inhibitor α; NF-kB—nuclear factor kB; p-JNK—phospho-c-Jun N-terminal kinase; p-ERK1/2—phospho-extracellular signal—regulated kinase 1 and 2; p38-MAPK—p38 mitogen-activated protein kinases; i.p.—intraperitoneal injection; XYL—xylene; PM—particulate matter; s.c.—subcutaniously; Nrf-2—nuclear factor erythroid 2-related factor 2; HO-1—heme oxygenase; RANKL/OPG—receptor activator of NF-κB ligand-osteoprotegerin; p-NIK—phospho-NF-kappa-B-inducing kinase; p-TAK1—phospho-transforming growth factor-β-activated kinase 1; UVB—ultraviolet-B; CoCl2—cobalt chloride; CCl4—carbon tetrachloride.