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.
Mar Drugs
2022 Nov 14;2011:. doi: 10.3390/md20110715.
Show Gene links
Show Anatomy links
Implication of Echinochrome A in the Plasticity and Damage of Intestinal Epithelium.
Ahn JS
,
Shin YY
,
Oh SJ
,
Song MH
,
Kang MJ
,
Park SY
,
Nguyen PT
,
Nguyen DK
,
Kim HK
,
Han J
,
Vasileva EA
,
Mishchenko NP
,
Fedoreyev SA
,
Stonik VA
,
Seo Y
,
Lee BC
,
Kim HS
.
???displayArticle.abstract???
The diverse therapeutic feasibility of the sea urchin-derived naphthoquinone pigment, Echinochrome A (Ech A), has been studied. Simple and noninvasive administration routes should be explored, to obtain the feasibility. Although the therapeutic potential has been proven through several preclinical studies, the biosafety of orally administered Ech A and its direct influence on intestinal cells have not been evaluated. To estimate the bioavailability of Ech A as an oral administration drug, small intestinal and colonic epithelial organoids were developed from mice and humans. The morphology and cellular composition of intestinal organoids were evaluated after Ech A treatment. Ech A treatment significantly increased the expression of LGR5 (~2.38-fold change, p = 0.009) and MUC2 (~1.85-fold change, p = 0.08). Notably, in the presence of oxidative stress, Ech A attenuated oxidative stress up to 1.8-fold (p = 0.04), with a restored gene expression of LGR5 (~4.11-fold change, p = 0.0004), as well as an increased expression of Ly6a (~3.51-fold change, p = 0.005) and CLU (~2.5-fold change, p = 0.01), markers of revival stem cells. In conclusion, Ech A is harmless to intestinal tissues; rather, it promotes the maintenance and regeneration of the intestinal epithelium, suggesting possible beneficial effects on the intestine when used as an oral medication.
22A0205L1-11 Ministry of Health and Welfare, 2018R1A5A2023879 National Research Foundation of Korea, 2019R1A2C2085876 National Research Foundation of Korea
Figure 1. Effect of Ech A on the mouse intestinal organoids. Mouse SIOs and COs were embedded in the extracellular matrix and cultured in the presence of 10 µM and 20 µM of Ech A for 4 days. (A) Bright-field images of mouse intestinal organoids treated with Ech A concentration of 0, 10, 20 µM. Upper panel: mSIOs, lower panel: mCOs. (B) Representative image of budding structure in mSIOs (left) and the quantification of budding structures (right). Arrows indicate budding structure. (C) Quantification of organoid formation in mSIOs (left) and mCOs (right). (D) Relative marker expression of differentiated intestinal epithelial cells in mSIOs and mCOs. Ech A: Echinochrome A, mSIO: mouse small intestinal organoid, mCO: mouse colon organoid, ISC: intestinal stem cell, PC: Paneth cell, GC: goblet cell, EC: enterocyte, RSC: revival stem cell, DCS: deep crypt secretory cell. Scale bar = 1 mm. All data represent the mean ± SD of the results from three independent experiments. ** p < 0.01.
Figure 2. Effect of Ech A on the human intestinal organoids. Human SIOs and COs were embedded in the extracellular matrix and cultured in the presence of 10 µM and 20 µM of Ech A for 5 days. (A) Bright-field images of human intestinal organoids treated with Ech A concentrations of 0, 10, 20 µM. Upper panel: hSIOs, lower panel: hCOs. (B) Quantification of organoid formation efficiency in hSIOs (left) and hCOs (right). (C) Relative marker expression of differentiated intestinal epithelial cells differentiation in hSIOs and hCOs. Ech A: Echinochrome A, hSIO: human small intestinal organoid, hCO: human colon organoid, ISC: intestinal stem cell, PC: Paneth cell, GC: goblet cell, EC: enterocyte, RSC: revival stem cell, DCS: deep crypt secretory cell. Scale bar = 1 mm. All data represent the mean ± SD of the results from three independent experiments. * p < 0.05.
Figure 3. Antioxidant effect of Ech A on oxidative damage-induced mouse intestinal organoids. Organoids were treated with 250 µM tBHP in the presence or absence of 20 µM Ech A for 4 h. (A) Flow cytometric analysis of ROS production by using ROS dye CellROX Deep Red assay and (B) mean fluorescence intensities (MFI) of CellROX-labeled cells in mSIOs and mCOs. Upper panel: mSIOs, lower panel: mCOs. (C) Relative gene expression level of ISC (Lgr5, Olfm4) and RSC (Clu, Ly6a) markers. Ech A: Echinochrome A, tBHP: tert-Butyl hydroperoxide, mSIO: mouse small intestinal organoid, mCO: mouse colon organoid, MFI: mean fluorescence intensities. * p < 0.05, ** p < 0.01.
Figure 4. Antioxidant effect of Ech A on oxidative damage-induced human intestinal organoids. Organoids were maintained for 5 days and then treated with 250 µM tBHP in the presence or absence of 20 µM Ech A for 4 h. (A) Flow cytometric analysis of ROS production by using ROS dye CellROX Deep Red assay and (B) mean fluorescence intensities (MFI) of CellROX-labeled cells in human SIOs and COs. Upper panel: hSIOs, lower panel: hCOs. (C) Relative gene expression level of ISC (LGR5, OLFM4) and RSC (CLU, ANXA1) markers. Ech A: Echinochrome A, tBHP: tert-Butyl hydroperoxide, hSIO: human small intestinal organoid, hCO: human colon organoid, MFI: mean fluorescence intensities. * p < 0.05, *** p < 0.001.
Artegiani,
Use and application of 3D-organoid technology.
2018, Pubmed
Artegiani,
Use and application of 3D-organoid technology.
2018,
Pubmed
Artyukov,
Marine Polyhydroxynaphthoquinone, Echinochrome A: Prevention of Atherosclerotic Inflammation and Probable Molecular Targets.
2020,
Pubmed
,
Echinobase
Ayyaz,
Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell.
2019,
Pubmed
Barker,
Identification of stem cells in small intestine and colon by marker gene Lgr5.
2007,
Pubmed
Beumer,
Regulation and plasticity of intestinal stem cells during homeostasis and regeneration.
2016,
Pubmed
Bhattacharyya,
Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases.
2014,
Pubmed
Buĭmov,
[Effect of the bioantioxidant histochrome on myocardial injury in reperfusion therapy on patients with myocardial infarction].
2002,
Pubmed
Crespo,
Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing.
2017,
Pubmed
Detel,
The influence of age on intestinal dipeptidyl peptidase IV (DPP IV/CD26), disaccharidases, and alkaline phosphatase enzyme activity in C57BL/6 mice.
2008,
Pubmed
Dutta,
Disease Modeling in Stem Cell-Derived 3D Organoid Systems.
2017,
Pubmed
Egorov,
[Histochrome, a new antioxidant, in the treatment of ocular diseases].
1999,
Pubmed
El Homsi,
Leptin modulates the expression of secreted and membrane-associated mucins in colonic epithelial cells by targeting PKC, PI3K, and MAPK pathways.
2007,
Pubmed
Fahmy,
Protective effect of Echinochrome against intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats.
2020,
Pubmed
Fedoreyev,
Antiviral and Antioxidant Properties of Echinochrome A.
2018,
Pubmed
,
Echinobase
Fujii,
Modeling Human Digestive Diseases With CRISPR-Cas9-Modified Organoids.
2019,
Pubmed
Gakhramanov,
Use of natural antioxidants for the correction of changes in general and local parameters of lipid peroxidation and antioxidant defense system during experimental eye burn.
2006,
Pubmed
Jang,
WNT/β-catenin pathway modulates the TNF-α-induced inflammatory response in bronchial epithelial cells.
2017,
Pubmed
Kim,
Induction of LGR5 by H2O2 treatment is associated with cell proliferation via the JNK signaling pathway in colon cancer cells.
2012,
Pubmed
Kim,
Multifaceted Clinical Effects of Echinochrome.
2021,
Pubmed
,
Echinobase
Kim,
Intestinal goblet cells and mucins in health and disease: recent insights and progress.
2010,
Pubmed
Lebedev,
Echinochrome, a naturally occurring iron chelator and free radical scavenger in artificial and natural membrane systems.
2005,
Pubmed
Lennikov,
Amelioration of endotoxin-induced uveitis treated with the sea urchin pigment echinochrome in rats.
2014,
Pubmed
,
Echinobase
Liu,
A role for intestinal alkaline phosphatase in preventing liver fibrosis.
2021,
Pubmed
Ma,
Crosstalk between Wnt/β-Catenin and NF-κB Signaling Pathway during Inflammation.
2016,
Pubmed
Min,
Gastrointestinal tract modeling using organoids engineered with cellular and microbiota niches.
2020,
Pubmed
Mischenko,
Effects of histochrom and emoxypin on biophysical properties of electroexitable cells.
2009,
Pubmed
Morris,
Reactive Oxygen Species in intestinal stem cell metabolism, fate and function.
2021,
Pubmed
Myant,
ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation.
2013,
Pubmed
Nath,
Reactive Oxygen Species in Modulating Intestinal Stem Cell Dynamics and Function.
2022,
Pubmed
Oh,
Echinochrome A Reduces Colitis in Mice and Induces In Vitro Generation of Regulatory Immune Cells.
2019,
Pubmed
,
Echinobase
Park,
Echinochrome A Treatment Alleviates Fibrosis and Inflammation in Bleomycin-Induced Scleroderma.
2021,
Pubmed
,
Echinobase
Park,
Echinochrome A Promotes Ex Vivo Expansion of Peripheral Blood-Derived CD34+ Cells, Potentially through Downregulation of ROS Production and Activation of the Src-Lyn-p110δ Pathway.
2019,
Pubmed
Prokopov,
Animal-derived medicinal products in Russia: Current nomenclature and specific aspects of quality control.
2019,
Pubmed
Puschhof,
Intestinal organoid cocultures with microbes.
2021,
Pubmed
Qu,
Establishment of intestinal organoid cultures modeling injury-associated epithelial regeneration.
2021,
Pubmed
Ramasamy,
Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis.
2011,
Pubmed
Regmi,
Heterospheroid formation improves therapeutic efficacy of mesenchymal stem cells in murine colitis through immunomodulation and epithelial regeneration.
2021,
Pubmed
Sato,
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.
2009,
Pubmed
Sayed,
Echinochrome pigment as novel therapeutic agent against experimentally - induced gastric ulcer in rats.
2018,
Pubmed
,
Echinobase
Seo,
Implication of Porphyromonas gingivalis in colitis and homeostasis of intestinal epithelium.
2019,
Pubmed
Seo,
Echinochrome A Improves Exercise Capacity during Short-Term Endurance Training in Rats.
2015,
Pubmed
,
Echinobase
Seol,
Echinochrome A Protects against Ultraviolet B-induced Photoaging by Lowering Collagen Degradation and Inflammatory Cell Infiltration in Hairless Mice.
2021,
Pubmed
Shvilkin,
[Effect of echinochrom on experimental myocardial reperfusion injury].
1991,
Pubmed
Soares,
The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases.
2010,
Pubmed
Sokolova,
Effects of Carrageenans on Biological Properties of Echinochrome.
2018,
Pubmed
,
Echinobase
Stelzner,
A nomenclature for intestinal in vitro cultures.
2012,
Pubmed
Sun,
The Caco-2 cell monolayer: usefulness and limitations.
2008,
Pubmed
Talalaeva,
[Identification of histochrome metabolism products in urine for studying drug pharmacokinetics].
2014,
Pubmed
Tuin,
Role of alkaline phosphatase in colitis in man and rats.
2009,
Pubmed
Van der Sluis,
Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection.
2006,
Pubmed
Wang,
Cathelicidin-WA Protects Against LPS-Induced Gut Damage Through Enhancing Survival and Function of Intestinal Stem Cells.
2021,
Pubmed
Watanabe,
Transplantation of intestinal organoids into a mouse model of colitis.
2022,
Pubmed
Workman,
Enhanced Utilization of Induced Pluripotent Stem Cell-Derived Human Intestinal Organoids Using Microengineered Chips.
2018,
Pubmed
Wu,
Transmissible gastroenteritis virus targets Paneth cells to inhibit the self-renewal and differentiation of Lgr5 intestinal stem cells via Notch signaling.
2020,
Pubmed
Yamashita,
Monolayer platform using human biopsy-derived duodenal organoids for pharmaceutical research.
2021,
Pubmed
Yermak,
Liposomal Form of the Echinochrome-Carrageenan Complex.
2018,
Pubmed
Yui,
YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration.
2018,
Pubmed
Yun,
Echinochrome A Treatment Alleviates Atopic Dermatitis-like Skin Lesions in NC/Nga Mice via IL-4 and IL-13 Suppression.
2021,
Pubmed
,
Echinobase
Zachos,
Human Enteroids/Colonoids and Intestinal Organoids Functionally Recapitulate Normal Intestinal Physiology and Pathophysiology.
2016,
Pubmed
Zakirova,
[The antioxidant histochrome: its effect on lipid peroxidation and the blood rheological properties in patients with unstable stenocardia].
1996,
Pubmed
Zhang,
Mechanism of endometrial MUC2 in reproductive performance in mice through PI3K/AKT signaling pathway after lipopolysaccharide treatment.
2022,
Pubmed
Zhao,
PI3K/Akt and Wnt/β-catenin Signaling Cross-regulate NF-κB Signaling in TNF-α-induced Human Lgr5+ Intestinal Stem Cells.
2022,
Pubmed
Zhou,
Infection of bat and human intestinal organoids by SARS-CoV-2.
2020,
Pubmed
Zietek,
Intestinal organoids for assessing nutrient transport, sensing and incretin secretion.
2015,
Pubmed
