Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Front Nutr
2022 Jan 01;9:888360. doi: 10.3389/fnut.2022.888360.
Show Gene links
Show Anatomy links
Antioxidant and Anti-inflammatory Extracts From Sea Cucumbers and Tunicates Induce a Pro-osteogenic Effect in Zebrafish Larvae.
Carletti A
,
Cardoso C
,
Lobo-Arteaga J
,
Sales S
,
Juliao D
,
Ferreira I
,
Chainho P
,
Dionísio MA
,
Gaudêncio MJ
,
Afonso C
,
Lourenço H
,
Cancela ML
,
Bandarra NM
,
Gavaia PJ
.
???displayArticle.abstract???
Bone metabolic disorders such as osteoporosis are characterized by the loss of mineral from the bone tissue leading to its structural weakening and increased susceptibility to fractures. A growing body of evidence suggests that inflammation and oxidative stress play an important role in the pathophysiological processes involved in the rise of these conditions. As the currently available therapeutic strategies are often characterized by toxic effects associated with their long-term use, natural antioxidants and anti-inflammatory compounds such as polyphenols promise to be a valuable alternative for the prevention and treatment of these disorders. In this scope, the marine environment is becoming an important source of bioactive compounds with potential pharmacological applications. Here, we explored the bioactive potential of three species of holothurians (Echinodermata) and four species of tunicates (Chordata) as sources of antioxidant and anti-inflammatory compounds with a particular focus on polyphenolic substances. Hydroethanolic and aqueous extracts were obtained from animals' biomass and screened for their content of polyphenols and their antioxidant and anti-inflammatory properties. Hydroethanolic fractions of three species of tunicates displayed high polyphenolic content associated with strong antioxidant potential and anti-inflammatory activity. Extracts were thereafter tested for their capacity to promote bone formation and mineralization by applying an assay that uses the developing operculum of zebrafish (Danio rerio) to assess the osteogenic activity of compounds. The same three hydroethanolic fractions from tunicates were characterized by a strong in vivo osteogenic activity, which positively correlated with their anti-inflammatory potential as measured by COX-2 inhibition. This study highlights the therapeutic potential of polyphenol-rich hydroethanolic extracts obtained from three species of tunicates as a substrate for the development of novel drugs for the treatment of bone disorders correlated to oxidative stress and inflammatory processes.
FIGURE 1. Scheme of the protocol used for the evaluation of the osteogenic activity.
FIGURE 2. Osteogenic activity of aqueous (A) and hydroethanolic (B) extracts from four species of tunicates in zebrafish larvae. Results are displayed as corrected operculum area (operculum area/head ratio) expressed as percentage of increase over the control. Representative image (C) of a fish treated with the negative control (ethanol), the positive control (Calcitriol 10 pg/mL) and the most powerful osteogenic extracts among tunicates (Aplidium sp. HE200). Statistical differences among the means were tested through one-way ANOVA followed by Dunnett’s multiple comparison test (p < 0.05) or, whenever normality and homoscedasticity weren’t met, through a non-parametric test followed by Dunn’s multiple comparison test (p < 0.05). P-values are indicated as follow: 0.0021. (**), < 0.0001 (****). HE, hydroethanolic extracts, AQ, aqueous extracts, 100–100 μg/mL, 200–200 μg/mL.
FIGURE 3. Osteogenic activity of aqueous (A) and hydroethanolic (B) extracts from three species of sea cucumbers in zebrafish larvae. Results are displayed as corrected operculum area (operculum area/head ratio) expressed as percentage of increase over the control. Representative image (C) of a fish treated with the negative control (ethanol), the positive control (Calcitriol 10 pg/mL) and the most powerful osteogenic extracts among holothurians (H. mammata HE200). Statistical differences among the means were tested through one-way ANOVA followed by Dunnett’s multiple comparison test (p < 0.05) or, whenever normality and homoscedasticity weren’t met, through a non-parametric test followed by Dunn’s multiple comparison test (p < 0.05). P-values are indicated as follow: 0.0332 (*), 0.0002 (***), < 0.0001 (****). HE, hydroethanolic extracts, AQ, aqueous extracts, 100–100 μg/mL, 200–200 μg/mL.
Ainsworth,
Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent.
2007, Pubmed
Ainsworth,
Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent.
2007,
Pubmed
Altschul,
Basic local alignment search tool.
1990,
Pubmed
Baharara,
The osteogenic differentiation stimulating activity of Sea cucumber methanolic crude extraction on rat bone marrow mesenchymal stem cells.
2014,
Pubmed
,
Echinobase
Belmiro,
Unfractionated heparin and new heparin analogues from ascidians (chordate-tunicate) ameliorate colitis in rats.
2009,
Pubmed
Bensimon-Brito,
Revisiting in vivo staining with alizarin red S--a valuable approach to analyse zebrafish skeletal mineralization during development and regeneration.
2016,
Pubmed
Benzie,
The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay.
1996,
Pubmed
Bergamin,
Nutraceuticals: Reviewing their Role in Chronic Disease Prevention and Management.
2019,
Pubmed
Bergen,
Zebrafish as an Emerging Model for Osteoporosis: A Primary Testing Platform for Screening New Osteo-Active Compounds.
2019,
Pubmed
Bonaccorsi,
Oxidative stress as a possible pathogenic cofactor of post-menopausal osteoporosis: Existing evidence in support of the axis oestrogen deficiency-redox imbalance-bone loss.
2018,
Pubmed
Bordbar,
High-value components and bioactives from sea cucumbers for functional foods--a review.
2011,
Pubmed
,
Echinobase
Briot,
Inflammatory diseases and bone fragility.
2017,
Pubmed
Bu,
Dried plum polyphenols attenuate the detrimental effects of TNF-alpha on osteoblast function coincident with up-regulation of Runx2, Osterix and IGF-I.
2009,
Pubmed
Carson,
Red algal extracts from Plocamium lyngbyanum and Ceramium secundatum stimulate osteogenic activities in vitro and bone growth in zebrafish larvae.
2018,
Pubmed
Cenci,
Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha.
2000,
Pubmed
Chakraborty,
Zebrafish: a complete animal model for in vivo drug discovery and development.
2009,
Pubmed
Compston,
Osteoporosis.
2019,
Pubmed
Deng,
Dexamethasone induces osteoblast apoptosis through ROS-PI3K/AKT/GSK3β signaling pathway.
2019,
Pubmed
Esmat,
Bioactive compounds, antioxidant potential, and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats.
2013,
Pubmed
,
Echinobase
Gilbert,
Inhibition of osteoblast differentiation by tumor necrosis factor-alpha.
2000,
Pubmed
Ha,
Reactive oxygen species mediate RANK signaling in osteoclasts.
2004,
Pubmed
Hofbauer,
Interleukin-1beta and tumor necrosis factor-alpha, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells.
1999,
Pubmed
Hughes,
Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-beta.
1996,
Pubmed
Kalu,
The ovariectomized rat model of postmenopausal bone loss.
1991,
Pubmed
Kedare,
Genesis and development of DPPH method of antioxidant assay.
2011,
Pubmed
Khotimchenko,
Pharmacological Potential of Sea Cucumbers.
2018,
Pubmed
,
Echinobase
Knopf,
Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin.
2011,
Pubmed
Kousteni,
Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity.
2001,
Pubmed
Krishnaiah,
New lamellarin alkaloids from the Indian ascidian Didemnum obscurum and their antioxidant properties.
2004,
Pubmed
Lobo,
Enhanced primers for amplification of DNA barcodes from a broad range of marine metazoans.
2013,
Pubmed
,
Echinobase
Lordan,
Marine bioactives as functional food ingredients: potential to reduce the incidence of chronic diseases.
2011,
Pubmed
MacRae,
Zebrafish as tools for drug discovery.
2015,
Pubmed
Manolagas,
From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis.
2010,
Pubmed
Martins,
The antioxidant activity of teas measured by the FRAP method adapted to the FIA system: optimising the conditions using the response surface methodology.
2013,
Pubmed
Pal,
Selective dietary polyphenols induce differentiation of human osteoblasts by adiponectin receptor 1-mediated reprogramming of mitochondrial energy metabolism.
2020,
Pubmed
Park,
Protective effects of green tea polyphenol against reactive oxygen species-induced oxidative stress in cultured rat calvarial osteoblast.
2003,
Pubmed
Pearce,
Anti-inflammatory thiazine alkaloids isolated from the New Zealand ascidian Aplidium sp.: inhibitors of the neutrophil respiratory burst in a model of gouty arthritis.
2007,
Pubmed
Ratnasingham,
A DNA-based registry for all animal species: the barcode index number (BIN) system.
2013,
Pubmed
Re,
Antioxidant activity applying an improved ABTS radical cation decolorization assay.
1999,
Pubmed
Reginster,
Osteoporosis: a still increasing prevalence.
2006,
Pubmed
Roberto,
Antioxidant, Mineralogenic and Osteogenic Activities of Spartina alterniflora and Salicornia fragilis Extracts Rich in Polyphenols.
2021,
Pubmed
Roggatz,
First report of the nutritional profile and antioxidant potential of Holothuria arguinensis, a new resource for aquaculture in Europe.
2016,
Pubmed
,
Echinobase
Santini,
Nutraceuticals: A paradigm of proactive medicine.
2017,
Pubmed
Scalbert,
Dietary polyphenols and the prevention of diseases.
2005,
Pubmed
Shahrulazua,
The In-Vitro Effects of Sea Cucumber (Stichopus sp1) Extract on Human Osteoblast Cell Line.
2013,
Pubmed
,
Echinobase
Singh,
Regeneration of amputated zebrafish fin rays from de novo osteoblasts.
2012,
Pubmed
Tarasco,
The zebrafish operculum: A powerful system to assess osteogenic bioactivities of molecules with pharmacological and toxicological relevance.
2017,
Pubmed
Tarasco,
ZFBONE: An ImageJ toolset for semi-automatic analysis of zebrafish bone structures.
2020,
Pubmed
To,
Rankl-induced osteoclastogenesis leads to loss of mineralization in a medaka osteoporosis model.
2012,
Pubmed
Trzeciakiewicz,
When nutrition interacts with osteoblast function: molecular mechanisms of polyphenols.
2009,
Pubmed
Usategui-Martín,
Polymorphisms in genes involved in inflammation, the NF-kB pathway and the renin-angiotensin-aldosterone system are associated with the risk of osteoporotic fracture. The Hortega Follow-up Study.
2020,
Pubmed
Weitzmann,
Estrogen deficiency and bone loss: an inflammatory tale.
2006,
Pubmed
White,
A simple radiochemical assay for prostaglandin synthetase.
1974,
Pubmed
Witten,
Features of mono- and multinucleated bone resorbing cells of the zebrafish Danio rerio and their contribution to skeletal development, remodeling, and growth.
2001,
Pubmed
Wright,
The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine.
2014,
Pubmed
Yousefzadeh,
Ovariectomized rat model of osteoporosis: a practical guide.
2020,
Pubmed
Zhang,
Tumor necrosis factor-alpha (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways.
2001,
Pubmed
Zhang,
Reactive oxygen species induce cell death via Akt signaling in rat osteoblast-like cell line ROS 17/2.8.
2015,
Pubmed
Zhou,
Oxidative Stress-Related Biomarkers in Postmenopausal Osteoporosis: A Systematic Review and Meta-Analyses.
2016,
Pubmed