Evaluation of the cardiotoxicity of Echinochrome A using human induced pluripotent stem cell-derived cardiac organoids.

Echinochrome A (EchA), a marine-derived natural product, has shown promise in treating cardiovascular and inflammatory diseases due to its antioxidant and anti-inflammatory properties. However, its cardiac safety remains underexplored. In this study, we utilized human induced pluripotent stem cell-derived cardiac organoids (hCOs) to validate their ability to model the cardiac safety profile of EchA in a human-relevant system.

Stichoposide C and Rhizochalin as Potential Aquaglyceroporin Modulators.

Aquaporins (AQPs) are a family of integral membrane proteins that selectively transport water and glycerol across the cell membrane. Because AQPs are involved in a wide range of physiological functions and pathophysiological conditions, AQP-based therapeutics may have the broad potential for clinical utility, including for disorders of water and energy balance. However, AQP modulators have not yet been developed as suitable candidates for clinical applications.

Sulfated Polyhydroxysteroid Glycosides from the Sea of Okhotsk Starfish and Potential Mechanisms for Their Observed Anti-Cancer Activity against Several Types of Human Cancer Cells.

Three new monosulfated polyhydroxysteroid glycosides, spiculiferosides A (), B (), and C (), along with new related unsulfated monoglycoside, spiculiferoside D (), were isolated from an ethanolic extract of the starfish collected in the Sea of Okhotsk. Compounds - contain two carbohydrate moieties, one of which is attached to C-3 of the steroid tetracyclic core, whereas another is located at C-24 of the side chain of aglycon. Two glycosides (, ) are biosides, and one glycoside (), unlike them, includes three monosaccharide residues.

New Rare Triterpene Glycosides from Pacific Sun Star, , and Their Anticancer Activity.

Six previously unknown triterpene glycosides, pacificusosides L-Q (-), and two previously known triterpene glycosides, cucumariosides B () and A (), were isolated from an alcoholic extract of Pacific sun star, . The structures of - were determined using 1D and 2D NMR, ESIMS, and chemical modifications. Compound is a rare type of triterpene glycoside with non-holostane aglycon, having a linear trisaccharide carbohydrate chain.

Fucosylated Chondroitin Sulfates with Rare Disaccharide Branches from the Sea Cucumbers and : Structures and Influence on Hematopoiesis.

Two fucosylated chondroitin sulfates were isolated from the sea cucumbers and using a conventional extraction procedure in the presence of papain, followed by anion-exchange chromatography on DEAE-Sephacel. Their composition was characterized in terms of quantitative monosaccharide and sulfate content, and structures were mainly elucidated using 1D- and 2D-NMR spectroscopy. As revealed by the data of the NMR spectra, both polysaccharides along with the usual fucosyl branches contained rare disaccharide branches α-D-GalNAc46-(1→2)-α-L-Fuc34 → attached to -3 of the GlcA of the backbone ( = H or SO).

Holothurian triterpene glycoside cucumarioside A-2 induces macrophages activation and polarization in cancer immunotherapy.

Background: Despite intensive developments of adoptive T cell and NK cell therapies, the efficacy against solid tumors remains elusive. Our study demonstrates that macrophage-based cell therapy could be a potent therapeutic option against solid tumors.

Methods: To this end, we determine the effect of a natural triterpene glycoside, cucumarioside A-2 (CA-2), on the polarization of mouse macrophages into the M1 phenotype, and explore the antitumor activity of the polarized macrophage.

Rhizochalinin Exhibits Anticancer Activity and Synergizes with EGFR Inhibitors in Glioblastoma In Vitro Models.

Rhizochalinin (Rhiz) is a recently discovered cytotoxic sphingolipid synthesized from the marine natural compound rhizochalin. Previously, Rhiz demonstrated high in vitro and in vivo efficacy in various cancer models. Here, we report Rhiz to be highly active in human glioblastoma cell lines as well as in patient-derived glioma-stem like neurosphere models.

Carbohydrate-Containing Low Molecular Weight Metabolites of Microalgae.

Microalgae are abundant components of the biosphere rich in low molecular weight carbohydrate-containing natural products (glycoconjugates). Glycoconjugates take part in the processes of photosynthesis, provide producers with important biological molecules, influence other organisms and are known by their biological activities. Some of them, for example, glycosylated toxins and arsenicals, are detrimental and can be transferred via food chains into higher organisms, including humans.

Assimiloside A, a Glycolipid with Immunomodulatory Activity from the Northwestern Pacific Marine Sponge .

Assimiloside A (), an unprecedented marine glycolipid containing a γ-lactone of 4,16,26-trihydroxy C fatty acid as an aglycon and a trisaccharide carbohydrate moiety, was isolated from the marine sponge . Its structure was elucidated by NMR spectroscopy, mass spectrometry, chemical transformations, and ECD spectroscopy combined with time-dependent density functional theory calculations. Assimiloside A at nontoxic concentrations of 0.

A Mass Spectrometry Database for Sea Cucumber Triterpene Glycosides.

Sea cucumber triterpene glycosides are a class of secondary metabolites that possess distinctive chemical structures and exhibit a variety of biological and pharmacological activities. The application of MS-based approaches for the study of triterpene glycosides allows rapid evaluation of the structural diversity of metabolites in complex mixtures. However, the identification of the detected triterpene glycosides can be challenging.

Djakonoviosides A, A, A, B-B - Triterpene Monosulfated Tetra- and Pentaosides from the Sea Cucumber : The First Finding of a Hemiketal Fragment in the Aglycones; Activity against Human Breast Cancer Cell Lines.

Seven new monosulfated triterpene glycosides, djakonoviosides A (), A (), A (), and B-B (-), along with three known glycosides found earlier in the other species, namely okhotoside A-1, cucumarioside A-1, and frondoside D, have been isolated from the far eastern sea cucumber (Cucumariidae, Dendrochirotida). The structures were established on the basis of extensive analysis of 1D and 2D NMR spectra and confirmed by HR-ESI-MS data. The compounds of groups A and B differ from each other in their carbohydrate chains, namely monosulfated tetrasaccharide chains are inherent to group A and pentasaccharide chains with one sulfate group, branched by C-2 Qui2, are characteristic of group B.

Echinochrome A Prevents Diabetic Nephropathy by Inhibiting the PKC-Iota Pathway and Enhancing Renal Mitochondrial Function in db/db Mice.

Echinochrome A (EchA) is a natural bioproduct extracted from sea urchins, and is an active component of the clinical drug, Histochrome. EchA has antioxidant, anti-inflammatory, and antimicrobial effects. However, its effects on diabetic nephropathy (DN) remain poorly understood.

Physicochemical characterization and phase II metabolic profiling of echinochrome A, a bioactive constituent from sea urchin, and its physiologically based pharmacokinetic modeling in rats and humans.

Echinochrome A, a natural naphthoquinone pigment found in sea urchins, is increasingly being investigated for its nutritional and therapeutic value associated with antioxidant, anticancer, antiviral, antidiabetic, and cardioprotective activities. Although several studies have demonstrated the biological effects and therapeutic potential of echinochrome A, little is known regarding its biopharmaceutical behaviors. Here, we aimed to investigate the physicochemical properties and metabolic profiles of echinochrome A and establish a physiologically-based pharmacokinetic (PBPK) model as a useful tool to support its clinical applications.

Multiple Effects of Echinochrome A on Selected Ion Channels Implicated in Skin Physiology.

Echinochrome A (Ech A), a naphthoquinoid pigment from sea urchins, is known to have anti-inflammatory and analgesic effects that have been suggested to be mediated by antioxidant activity and intracellular signaling modulation. In addition to these mechanisms, the ion channels in keratinocytes, immune cells, and nociceptive neurons may be the target for the pharmacological effects. Here, using the patch clamp technique, we investigated the effects of Ech A on the Ca-permeable TRPV3, TRPV1 and Orai1 channels and the two-pore domain K (K2P) channels (TREK/TRAAK, TASK-1, and TRESK) overexpressed in HEK 293 cells.

Biological Activity and Probable Mechanisms of Action of Derivatives of Tryptanthrin and Mostotrin Alkaloids.

The alkaloid tryptanthrin and its water-soluble derivative mostotrin exhibit high antimicrobial and antitumor activity. To develop more active and less toxic preparations, syntheses and testing of the biological activities of a number of new and/or little-studied analogs were performed. Some of them have been shown to have higher cytotoxicity against tumor and microbial cells than tryptanthrin and mostotrin.

Novel GSK-3β Inhibitor Neopetroside A Protects Against Murine Myocardial Ischemia/Reperfusion Injury.

Recent trends suggest novel natural compounds as promising treatments for cardiovascular disease. The authors examined how neopetroside A, a natural pyridine nucleoside containing an α-glycoside bond, regulates mitochondrial metabolism and heart function and investigated its cardioprotective role against ischemia/reperfusion injury. Neopetroside A treatment maintained cardiac hemodynamic status and mitochondrial respiration capacity and significantly prevented cardiac fibrosis in murine models.

Regulation of Inflammation-Mediated Endothelial to Mesenchymal Transition with Echinochrome a for Improving Myocardial Dysfunction.

Endothelial-mesenchymal transition (EndMT) is a process by which endothelial cells (ECs) transition into mesenchymal cells (e.g., myofibroblasts and smooth muscle cells) and induce fibrosis of cells/tissues, due to ischemic conditions in the heart.

Effect of Echinochrome A on Submandibular Gland Dysfunction in Ovariectomized Rats.

Post-menopausal dry mouth or xerostomia is caused by reduced salivary secretion. This study aimed to investigate the efficacy of echinochrome A (Ech A) in alleviating submandibular gland dysfunctions in ovariectomized rats that mimic menopause. Female rats that were eight-weeks-old were randomly divided into SHAM-6, -12; OVX-6, -12; and ECH-6, -12 groups (consisting of 6- and 12-weeks post-sham-operated, ovariectomized, and Ech A-treated ovariectomized rats, respectively).

Echinochrome A Reverses Kidney Abnormality and Reduces Blood Pressure in a Rat Model of Preeclampsia.

We aimed to observe the effects of Echinochrome A (Ech A) on systemic changes using a rat model of preeclampsia. The results showed that an infusion of angiotensin II (Ang II) through an osmotic pump (1 μg/kg/min) on GD 8 increased systolic and diastolic blood pressures and reduced fetal weight and placental weight. The diameters of the glomeruli were expended and glomeruli capillaries were diminished.

Implication of Echinochrome A in the Plasticity and Damage of Intestinal Epithelium.

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.

Echinochrome A Inhibits Melanogenesis in B16F10 Cells by Downregulating CREB Signaling.

Excessive increase in melanin pigment in the skin can be caused by a variety of environmental factors, including UV radiation, and can result in spots, freckles, and skin cancer. Therefore, it is important to develop functional whitening cosmetic reagents that regulate melanogenesis. In this study, we investigated the effects of echinochrome A (Ech A) on melanogenesis in the B16F10 murine melanoma cell line.

1--Alkylglycerol Ethers from the Marine Sponge and Their Cytotoxic Activity.

The cytotoxicity-bioassay-guided fractionation of the ethanol extract from the marine sponge , whose 1--alkyl--glycerol ethers (AGEs) have not been investigated so far, led to the isolation of a complex lipid fraction containing, along with previously known compounds, six new lipids of the AGE type. The composition of the AGE fraction as well as the structures of 6 new and 22 previously known compounds were established using H and C NMR, GC/MS, and chemical conversion methods. The new AGEs were identified as: 1--(Z-docos-15-enyl)--glycerol (), 1--(Z-docos-17-enyl)--glycerol (), 1--(Z-tricos-15-enyl)--glycerol (), 1--(Z-tricos-16-enyl)--glycerol (), 1--(Z-tricos-17-enyl)--glycerol (), and 1--(Z-tetracos-15-enyl)--glycerol ().