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Nutrients
2020 Jun 06;126:. doi: 10.3390/nu12061698.
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A Glycosaminoglycan-Rich Fraction from Sea Cucumber Isostichopus badionotus Has Potent Anti-Inflammatory Properties In Vitro and In Vivo.
Olivera-Castillo L
,
Grant G
,
Kantún-Moreno N
,
Barrera-Pérez HA
,
Montero J
,
Olvera-Novoa MA
,
Carrillo-Cocom LM
,
Acevedo JJ
,
Puerto-Castillo C
,
May Solís V
,
Pérez-Vega JA
,
Gil-Zamorano J
,
Hernández-Garibay E
,
Fernández-Herrera MA
,
Pérez-Tapia M
,
Medina-Contreras O
,
Villanueva-Toledo JR
,
Rodriguez-Canul R
,
Dávalos A
.
Abstract
Sea cucumber body wall contains several naturally occurring bioactive components that possess health-promoting properties. Isostichopus badionotus from Yucatan, Mexico is heavily fished, but little is known about its bioactive constituents. We previously established that I. badionotus meal had potent anti-inflammatory properties in vivo. We have now screened some of its constituents for anti-inflammatory activity in vitro. Glycosaminoglycan and soluble protein preparations reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammatory responses in HaCaT cells while an ethanol extract had a limited effect. The primary glycosaminoglycan (fucosylated chondroitin sulfate; FCS) was purified and tested for anti-inflammatory activity in vivo. FCS modulated the expression of critical genes, including NF-ĸB, TNFα, iNOS, and COX-2, and attenuated inflammation and tissue damage caused by TPA in a mouse ear inflammation model. It also mitigated colonic colitis caused in mice by dextran sodium sulfate. FCS from I. badionotus of the Yucatan Peninsula thus had strong anti-inflammatory properties in vivo.
Figure 1. Extracts (crude GAGs, soluble proteins, ethanol soluble) from the body wall of I. badionotus inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced proliferation of HaCat [human keratinocyte] cells in culture (a). Purified GAGs (3 μg/mL) limit TPA-mediated production of Interferon gamma (IFNγ)-positive HaCaT cells (b). N ≥ 4 per group and values with distinct superscripts differ significantly from each other (p ≤ 0.05).
Figure 2. GAGs preparation isolated from I. badionotus body wall. (a) Alcian Blue-stained polyacrylamide gel electrophoretogram of initial and purified GAGs from sea cucumber (I. badionotus). (b) 1H NMR spectra at 600 MHz of fucosylated chondroitin sulfate of sea cucumber (I. badionatus). (c) Infrared spectra of GAGs from sea cucumber (I. badionotus). (d) Overlay comparing GAGs to standards.
Figure 3. GAGs from sea cucumber (I. badionotus) body wall exert anti-inflammatory effects in a mouse ear inflammation model. Mouse ears exposed to vehicle (control, left ear), or inflammatory agent TPA alone, or TPA followed by dexamethasone (DXA) or GAGs (right ear). (a) Representative photomicrographs of transverse section of mouse ears sensitized with TPA or TPA and test substance, stained with haematoxylin-eosin (magnification 10X). Images are representative of five mice with similar results. (b) Differences in ear weights (right–left) after treatment with TPA or TPA and test substance; n ≥ 5 per group. (c) Histological score for ear micrographs in (a); values are the mean ± SEM, n = 3 per group. (d) Differences in ear weights (right–left) after treatment with TPA or TPA and shark cartilage (CSS); n ≥ 3 per group. Values with distinct superscripts differ significantly from each other (p ≤ 0.05).
Figure 4. GAGs from sea cucumber (I. badionotus) target principal inflammation-related genes. Mouse ears were exposed to vehicle alone (left ear), GAGs, inflammatory agent TPA followed by GAGs, or TPA followed by dexamethasone (DXA) as an anti-inflammatory control (right ear). Genes NF kappa B (NF-ĸB), IL-6, TNF alpha (TNFα), iNOS, IL-10, IL-11, COX-2 and STAT3 were evaluated by qRT-PCR. Values (fold change) are the mean ± SD. Values with distinct superscripts differ significantly from each other (p < 0.05).
Figure 5. GAGs from sea cucumber (I. badionotus) with sulfate levels of 4.5% or above have similar anti-inflammatory properties. (a) The sulfate content of freshly-isolated GAGs used in analyses was quantified. The GAGs—LS were derived from the same sample but were reconstituted and lyophilized at least 3 times prior to sulfate analysis. (b) Differences in ear weights (right-left) in mouse ears exposed to vehicle alone (left ear), or inflammatory agent TPA followed by GAGs or GAGs—LS [low sulfate] (right ear). For each figure, n ≥ 4 per group and values with distinct superscripts differ significantly from each other (p ≤ 0.05).
Figure 6. Orally-administered GAGs from sea cucumber (I. badionotus) body wall exert anti-inflammatory effects on Dextran sodium Sulfate (DSS)-colitis in mice. DSS (25 g/L in drinking water) was offered mice for four days, followed by water alone for two days. A proportion of the mice were dosed daily with GAGS (80 mg/kg body weight (BW)/d) for one day prior to and during the experimental period. (a) Weight change in mice dosed with DSS ± co-treatment with GAGs. (b) Colonic TNFα gene expression in mice dosed with DSS ± co-treatment with GAGs. (c) Colon lengths in mice dosed with DSS ± co-treatment with GAGs. (d) Small intestine lengths in mice dosed with DSS ± co-treatment with GAGs. For each figure, n ≥ 4 per group and values with distinct superscripts differ significantly from each other (p ≤ 0.05).
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