Structure-Based In Silico Screening of Marine Phlorotannins for Potential Walrus Calicivirus Inhibitor.

A new calicivirus isolated from a walrus was reported in 2004. Since unknown marine mammalian zoonotic viruses could pose great risks to human health, this study aimed to develop therapeutic countermeasures to quell any potential outbreak of a pandemic caused by this virus. We first generated a 3D model of the walrus calicivirus capsid protein and identified compounds from marine natural products, especially phlorotannins, as potential walrus calicivirus inhibitors. A 3D model of the target protein was generated using homology modeling based on two publicly available template sequences. The sequence of the capsid protein exhibited 31.3% identity and 42.7% similarity with the reference templates. The accuracy and reliability of the predicted residues were validated via Ramachandran plotting. Molecular docking simulations were performed between the capsid protein 3D model and 17 phlorotannins. Among them, five phlorotannins demonstrated markedly stable docking profiles; in particular, 2,7-phloroglucinol-6,6-bieckol showed favorable structural integrity and stability during molecular dynamics simulations. The results indicate that the phlorotannins are promising walrus calicivirus inhibitors. Overall, the study findings showcase the rapid turnaround of in silico-based drug discovery approaches, providing useful insights for developing potential therapies against novel pathogenic viruses, especially when the 3D structures of the viruses remain experimentally unknown.

Antioxidant Effects of Turbo cornutus By-Products Visceral Extract against Hydrogen Peroxide-Induced Oxidative Stress by Regulating MAPK and Akt Signaling Pathways in Vero Cells.

Turbo cornutus, a marine gastropod mollusk commonly called sea snail, is found along the southern coast of Korea and holds considerable importance as a marine food resource, particularly on Jeju Island, Korea. Data are scarce on the antioxidant activity of hot water extracts from T. cornutus visceral tissue. Therefore, this study was performed to evaluate the antioxidant activities of T. cornutus visceral tissue hot water extract (TVE) and the underlying mechanisms against hydrogen peroxide-induced oxidative stress in Vero cells. The amino acid composition and antioxidant effects of TVE were evaluated. Furthermore, the impact of TVE on the expression of proteins within the mitogen-activated protein kinase (MAPK) pathway is investigated. TVE showed a concentration-dependent enhancement in its scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (IC50 = 1.07 ± 0.06 mg/mL) and hydrogen peroxide (IC50 = 0.33 ± 0.03 mg/mL). TVE reduced intracellular reactive oxygen species (ROS) production and maintained cell viability under H2O2-induced oxidative stress by suppressing apoptosis in Vero cells. Additionally, TVE demonstrated regulatory effects on the MAPK and protein kinase B (Akt) signaling pathways activated by H2O2. In conclusion, the findings from our study propose that TVE holds potential as a bioactive component in the formulation of functional foods.

Short-range end resection requires ATAD5-mediated PCNA unloading for faithful homologous recombination.

Homologous recombination (HR) requires bidirectional end resection initiated by a nick formed close to a DNA double-strand break (DSB), dysregulation favoring error-prone DNA end-joining pathways. Here we investigate the role of the ATAD5, a PCNA unloading protein, in short-range end resection, long-range resection not being affected by ATAD5 deficiency. Rapid PCNA loading onto DNA at DSB sites depends on the RFC PCNA loader complex and MRE11-RAD50-NBS1 nuclease complexes bound to CtIP. Based on our cytological analyses and on an in vitro system for short-range end resection, we propose that PCNA unloading by ATAD5 is required for the completion of short-range resection. Hampering PCNA unloading also leads to failure to remove the KU70/80 complex from the termini of DSBs hindering DNA repair synthesis and the completion of HR. In line with this model, ATAD5-depleted cells are defective for HR, show increased sensitivity to camptothecin, a drug forming protein-DNA adducts, and an augmented dependency on end-joining pathways. Our study highlights the importance of PCNA regulation at DSB for proper end resection and HR.

Purification and Molecular Docking Study on the Angiotensin I-Converting Enzyme (ACE)-Inhibitory Peptide Isolated from Hydrolysates of the Deep-Sea Mussel Gigantidas vrijenhoeki.

The objective of this study was to prepare an angiotensin I-converting enzyme (ACE)-inhibitory peptide from the hydrothermal vent mussel, Gigantidas vrijenhoeki. The G. vrijenhoeki protein was hydrolyzed by various hydrolytic enzymes. The peptic hydrolysate exhibited the highest ACE-inhibitory activity and was fractionated into four molecular weight ranges by ultrafiltration. The <1 kDa fraction exhibited the highest ACE inhibitory activity and was found to have 11 peptide sequences. Among the analyzed peptides, KLLWNGKM exhibited stronger ACE inhibitory activity and an IC50 value of 0.007 µM. To investigate the ACE-inhibitory activity of the analyzed peptides, a molecular docking study was performed. KLLWNGKM exhibited the highest binding energy (-1317.01 kcal/mol), which was mainly attributed to the formation of hydrogen bonds with the ACE active pockets, zinc-binding motif, and zinc ion. These results indicate that G. vrijenhoeki-derived peptides can serve as nutritional and pharmacological candidates for controlling blood pressure.

Angiotensin I-Converting Enzyme (ACE) Inhibition and Molecular Docking Study of Meroterpenoids Isolated from Brown Alga, Sargassum macrocarpum.

Angiotensin I-converting enzyme (ACE) is an important blood pressure regulator. In this study, we aimed to investigate the ACE-inhibitory effects of meroterpenoids isolated from the brown alga, Sargassum macrocarpum, and the molecular mechanisms underlying ACE inhibition. Four fractions of S. macrocarpum were prepared using hexane, chloroform, ethyl acetate, and water as solvents and analyzed for their potential ACE-inhibitory effects. The chloroform fraction showed the strongest ACE-inhibitory effect, with an IC50 value of 0.18 mg/mL. Three meroterpenoids, sargachromenol, 7-methyl sargachromenol, and sargaquinoic acid, were isolated from the chloroform fraction. Meroterpenoids isolated from S. macrocarpum had IC50 values of 0.44, 0.37, and 0.14 mM. The molecular docking study revealed that the ACE-inhibitory effect of the isolated meroterpenoids was mainly attributed to Zn-ion, hydrogen bonds, pi-anion, and pi-alkyl interactions between the meroterpenoids and ACE. These results suggest that S. macrocarpum could be a potential raw material for manufacturing antihypertensive nutraceutical ingredients.

Antioxidant, Antiviral, and Anti-Inflammatory Activities of Lutein-Enriched Extract of Tetraselmis Species.

Microalgae are proposed to have powerful applications for human health in the pharmaceutical and food industries. Tetraselmis species (sp.), which are green microalgae, were identified as a source of broad-spectrum health-promoting biological activities. However, the bioactivity of these species has not been elucidated. We aimed to confirm the antioxidant, antiviral, and anti-inflammatory effects of Tetraselmis sp. extract (TEE). TEE showed 2,2-diphenyl-1-picryl-hydrazyl-hydrate radical and hydrogen peroxide scavenging activities and reduced plaque formation in Vero E6 cells infected with vaccinia virus. TEE treatment also significantly inhibited nitric oxide (NO) production and improved cell viability in lipopolysaccharide (LPS)-induced RAW264.7 cells. These anti-inflammatory effects were further analyzed in LPS-induced RAW 264.7 cells and the zebrafish model. Further, TEE reduced induced NO synthase expression and proinflammatory cytokine release, including tumor necrosis factor-α, interleukin-6, and interleukin-1ß, through MAPKs and NF-κB-dependent mechanisms. Further analysis revealed that TEE increased the survival rate and reduced cell death and NO production in an LPS-stimulated zebrafish model. Further, high-performance liquid chromatography revealed a strong presence of the carotenoid lutein in TEE. Overall, the results suggest that lutein-enriched TEE may be a potent antioxidant, antiviral, and anti-inflammatory agent that could be sustainably utilized in industrial applications.

In Silico Virtual Screening of Marine Aldehyde Derivatives from Seaweeds against SARS-CoV-2.

Coronavirus disease 2019, caused by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global pandemic that poses an unprecedented threat to the global economy and human health. Several potent inhibitors targeting SARS-CoV-2 have been published; however, most of them have failed in clinical trials. This study aimed to assess the therapeutic compounds among aldehyde derivatives from seaweeds as potential SARS-CoV-2 inhibitors using a computer simulation protocol. The absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties of the compounds were analyzed using a machine learning algorithm, and the docking simulation of these compounds to the 3C-like protease (Protein Data Bank (PDB) ID: 6LU7) was analyzed using a molecular docking protocol based on the CHARMm algorithm. These compounds exhibited good drug-like properties following the Lipinski and Veber rules. Among the marine aldehyde derivatives, 4-hydroxybenzaldehyde, 3-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, and 5-bromoprotocatechualdehyde were predicted to have good absorption and solubility levels and non-hepatotoxicity in the ADME/Tox prediction. 3-hydroxybenzaldehyde and 3,4-dihydroxybenzaldehyde were predicted to be non-toxic in TOPKAT prediction. In addition, 3,4-dihydroxybenzaldehyde was predicted to exhibit interactions with the 3C-like protease, with binding energies of -71.9725 kcal/mol. The computational analyses indicated that 3,4-dihydroxybenzaldehyde could be regarded as potential a SARS-CoV-2 inhibitor.

Anti-Inflammatory Effect of Turbo cornutus Viscera Ethanolic Extract against Lipopolysaccharide-Stimulated Inflammatory Response via the Regulation of the JNK/NF-kB Signaling Pathway in Murine Macrophage RAW 264.7 Cells and a Zebrafish Model: A Preliminary Study.

Turbo cornutus, the horned turban sea snail, is found along the intertidal and basaltic shorelines and is an important fishery resource of Jeju Island. In this study, we performed a preliminary study on anti-inflammatory effect of 70% ethanol extract obtained from T. cornutus viscera (TVE) on lipopolysaccharide (LPS)-stimulated RAW264.7 cells in vitro and zebrafish embryos in vivo. TVE reduced the production of LPS-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) without any toxic effects. TVE also decreased the protein expression of LPS-induced inducible NO synthase and cyclooxygenase-2 and suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß. Furthermore, mechanistic studies indicated that TVE suppressed c-Jun N-terminal kinase phosphorylation and nuclear factor-kB activation. In zebrafish embryos, TVE did not show developmental toxicity based on the survival rate and cell death findings. In LPS-stimulated zebrafish embryos, TVE suppressed NO production and cell death. In conclusion, the result from this preliminary study showed TVE has a potential anti-inflammatory property that can be exploited as a functional food ingredient.

Identifying Potential Antioxidant Properties from the Viscera of Sea Snails (Turbo cornutus).

Turbo cornutus, the horned turban sea snail, is found along the intertidal and basaltic shorelines of Jeju Island, Korea. T. cornutus feeds on seaweeds (e.g., Undaria sp., and Ecklonia sp.) composed of diverse antioxidants. This study identified potential antioxidant properties from T. cornutus viscera tissues. Diverse extracts were evaluated for their hydrogen peroxide (H2O2) scavenging activities. T. cornutus viscera protamex-assisted extracts (TVP) were purified by gel filtration chromatography (GFC), and potential antioxidant properties were analyzed for their amino acid sequences and its peroxidase inhibition effects by in silico molecular docking and in vitro analysis. According to the results, T. cornutus viscera tissues are composed of many protein contents with each over 50%. Among the extracts, TVP possessed the highest H2O2 scavenging activity. In addition, TVP-GFC-3 significantly decreased intracellular reactive oxygen species (ROS) levels and increased cell viability in H2O2-treated HepG2 cells without cytotoxicity. TVP-GFC-3 comprises nine low molecular bioactive peptides (ELR, VGPQ, TDY, ALPHA, PAH, VDY, WSDK, VFSP, and FAPQY). Notably, the peptides dock to the active site of the myeloperoxidase (MPO), especially TDY and FAPQY showed the MPO inhibition effects with IC50 values of 646.0 ± 45.0 µM and 57.1 ± 17.7 µM, respectively. Altogether, our findings demonstrated that T. cornutus viscera have potential antioxidant properties that can be used as high value-added ingredients.

The Effects of Marine Algal Polyphenols, Phlorotannins, on Skeletal Muscle Growth in C2C12 Muscle Cells via Smad and IGF-1 Signaling Pathways.

Skeletal muscle is an important tissue in energy metabolism and athletic performance. The use of effective synthetic supplements and drugs to promote muscle growth is limited by various side effects. Moreover, their use is prohibited by anti-doping agencies; hence, natural alternatives are needed. Therefore, we evaluated the muscle growth effect of substances that can act like synthetic supplements from edible marine algae. First, we isolated six marine algal polyphenols belonging to the phlorotannin class, namely dieckol (DK), 2,7″-phloroglucinol-6,6'-bieckol (PHB), phlorofucofuroeckol A (PFFA), 6,6'-bieckol (6,6-BK), pyrogallol-phloroglucinol-6,6'-bieckol (PPB), and phloroglucinol (PG) from an edible brown alga, Ecklonia cava and evaluated their effects on C2C12 myoblasts proliferation and differentiation. Of the six phlorotannin isolates evaluated, DK and PHB induced the highest degree of C2C12 myoblast proliferation. In addition, DK and PHB regulates myogenesis by down-regulating the Smad signaling, a negative regulator, and up-regulating the insulin-like growth factor-1 (IGF-1) signaling, a positive regulator. Interestingly, DK and PHB bind strongly to myostatin, which is an inhibitor of myoblast proliferation, while also binding to IGF-1 receptors. Moreover, they bind to IGF-1 receptor. These results suggest that DK and PHB are potential natural muscle building supplements and could be a safer alternative to synthetic drugs.

Potential Antioxidant Properties of Enzymatic Hydrolysates from Stichopus japonicus against Hydrogen Peroxide-Induced Oxidative Stress.

A comprehensive antioxidant evaluation was performed on enzymatic hydrolysates of Stichopus japonicus (S. japonicus) using Vero cells and zebrafish models for in vitro and in vivo studies, respectively. S. japonicus was hydrolyzed with food-grade enzymes (alcalase, α-chymotrypsin, flavourzyme, kojizyme, neutrase, papain, pepsin, protamex, and trypsin), and the free radical scavenging activities were screened via electron spin resonance (ESR) spectroscopy. According to the results, the enzymatic hydrolysates contained high protein and relatively low polysaccharide and sulfate contents. Among these hydrolysates, the α-chymotrypsin assisted hydrolysate from S. japonicus (α-chy) showed high yield and protein content, and strong hydroxyl radical scavenging activity. Therefore, α-chy was chosen for further purification. The α-chy was fractionated by ultrafiltration into three ultrafiltration (UF) fractions based on their molecular weight: >10 kDa (α-chy-I), 5-10 kDa (α-chy-II), and <5 kDa (α-chy-III), and we evaluated their antioxidant properties in H2O2 exposed Vero cells. The α-chy and its UF fractions significantly decreased the intracellular reactive oxygen species (ROS) generation and increased cell viability in H2O2 exposed Vero cells. Among them, α-chy-III effectively declined the intracellular ROS levels and increased cell viability and exhibited protection against H2O2 induced apoptotic damage. Furthermore, α-chy-III remarkably attenuated the cell death, intracellular ROS and lipid peroxidation in H2O2 exposed zebrafish embryos. Altogether, our findings demonstrated that α-chy and its α-chy-III from S. japonicus possess strong antioxidant activities that could be utilized as a bioactive ingredient for functional food industries.

ATAD5 restricts R-loop formation through PCNA unloading and RNA helicase maintenance at the replication fork.

R-loops are formed when replicative forks collide with the transcriptional machinery and can cause genomic instability. However, it is unclear how R-loops are regulated at transcription-replication conflict (TRC) sites and how replisome proteins are regulated to prevent R-loop formation or mediate R-loop tolerance. Here, we report that ATAD5, a PCNA unloader, plays dual functions to reduce R-loops both under normal and replication stress conditions. ATAD5 interacts with RNA helicases such as DDX1, DDX5, DDX21 and DHX9 and increases the abundance of these helicases at replication forks to facilitate R-loop resolution. Depletion of ATAD5 or ATAD5-interacting RNA helicases consistently increases R-loops during the S phase and reduces the replication rate, both of which are enhanced by replication stress. In addition to R-loop resolution, ATAD5 prevents the generation of new R-loops behind the replication forks by unloading PCNA which, otherwise, accumulates and persists on DNA, causing a collision with the transcription machinery. Depletion of ATAD5 reduces transcription rates due to PCNA accumulation. Consistent with the role of ATAD5 and RNA helicases in maintaining genomic integrity by regulating R-loops, the corresponding genes were mutated or downregulated in several human tumors.

Structural Evidence for Antihypertensive Effect of an Antioxidant Peptide Purified from the Edible Marine Animal Styela clava.

This study investigated the antihypertensive effects of an antioxidant peptide, Leu-Trp-His-Thr-His (LWHTH), purified from Styela clava peptic hydrolysate, to assess the bioactivity of the peptide and verify the value of S. clava as a health-promoting food. Also, the study presented structural evidence for the effects of LWHTH. The inhibitory effect of LWHTH on angiotensin I-converting enzyme (ACE) was assessed using enzyme reaction methods and the simulation methods in computational space. LWHTH inhibited ACE with an IC50 value of 16.42 ± 0.45 µM. The LWHTH structure was stable, and its ACE inhibitory effect was retained under simulated gastrointestinal conditions. In silico simulations revealed that LWHTH binds the active site of ACE, with residues LW making the ACE-LWHTH complex stable and residues HTH making the complex strong. Furthermore, LWHTH significantly reduced blood pressure in spontaneously hypertensive rats. These results demonstrate that LWHTH has the potential to be a healthy functional food with antihypertensive effects. Therefore, S. clava consumption may be beneficial for human health.

ATAD5 promotes replication restart by regulating RAD51 and PCNA in response to replication stress.

Maintaining stability of replication forks is important for genomic integrity. However, it is not clear how replisome proteins contribute to fork stability under replication stress. Here, we report that ATAD5, a PCNA unloader, plays multiple functions at stalled forks including promoting its restart. ATAD5 depletion increases genomic instability upon hydroxyurea treatment in cultured cells and mice. ATAD5 recruits RAD51 to stalled forks in an ATR kinase-dependent manner by hydroxyurea-enhanced protein-protein interactions and timely removes PCNA from stalled forks for RAD51 recruitment. Consistent with the role of RAD51 in fork regression, ATAD5 depletion inhibits slowdown of fork progression and native 5-bromo-2'-deoxyuridine signal induced by hydroxyurea. Single-molecule FRET showed that PCNA itself acts as a mechanical barrier to fork regression. Consequently, DNA breaks required for fork restart are reduced by ATAD5 depletion. Collectively, our results suggest an important role of ATAD5 in maintaining genome integrity during replication stress.

Bis (3-bromo-4,5-dihydroxybenzyl) ether, a novel bromophenol from the marine red alga Polysiphonia morrowii that suppresses LPS-induced inflammatory response by inhibiting ROS-mediated ERK signaling pathway in RAW 264.7 macrophages.

Inflammation is a pathophysiological defense response against various factors for maintaining homeostasis in the body. However, when continued excessive inflammation becomes chronic, various chronic diseases can develop. Therefore, effective treatment before chronic inflammation development is essential. Bis (3-bromo-4,5-dihydroxybenzyl) ether (BBDE, C14H12Br2O5) is a novel bromophenol isolated from the red alga Polysiphonia morrowii. The beneficial physiological functions of various bromophenols are known, but whether BBDE has beneficial physiological functions is unknown. Therefore, we first investigated whether BBDE exerts any anti-inflammatory effect. We demonstrated that BBDE inhibits inflammation by reducing inflammatory mediators, such as nitric oxide, prostaglandin E2, iNOS, COX2, and pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, and interleukin-6), in LPS-induced macrophage cells. To examine the mechanism of action by which BBDE inhibits inflammation, we confirmed its effect on signal transduction and ROS generation. BBDE selectively inhibited ERK phosphorylation in the mitogen-activated protein kinase pathways. Moreover BBDE suppressed LPS-induced ROS generation in RAW 264.7 macrophage cells. Inhibition of LPS-induced ROS generation by BBDE also caused ERK inactivation and an inflammatory reaction. Therefore, BBDE inhibits LPS-induced inflammation by inhibiting the ROS-mediated ERK signaling pathway in RAW 264.7 macrophage cells and thus can be useful for treating inflammatory diseases.

Protective Effects of An Water Extracts Prepared from Loliolus beka Gray Meat Against H2O2-Induced Oxidative Stress in Chang Liver Cells and Zebrafish Embryo Model.

In this study, we first evaluated protective effects of Loliolus beka in a human liver cell line and zebrafish embryo model with its anti-oxidant activity. First, we prepared the water extract from L. beka meat (LBMW) at room temperature for 24 h and revealed it consisted of a rich taurine. LBMW exhibited the scavenging effects against 2,2-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and hydrogen peroxide (H2O2) as well as the high value of oxygen radical absorbance capacity (ORAC). Also, the hydroxyl radical-induced DNA damage was dose-dependently reduced by the treatment of LBMW. In addition, LBMW showed no cytotoxicity and reduced the production of reactive oxygen species (ROS) in H2O2-treated hepatocytes. Moreover, LBMW regulated the expression of an anti-apoptotic molecule, Bcl-2 and the expression of pro-apoptotic molecules, Bax and PARP in H2O2-treated hepatocytes as well as the increment of antioxidant mediated-HO-1 and Nrf2 protein expression. In further study, LBMW improved the survival rate and decreased the production of ROS in H2O2-treated zebrafish embryo model. Therefore, our results suggest that Loliolus beka has protective effects against H2O2-induced oxidative stress and may be used as a potential source for functional foods.

Protective Effects of An Enzymatic Hydrolysate from Octopus ocellatus Meat against Hydrogen Peroxide-Induced Oxidative Stress in Chang Liver Cells and Zebrafish Embryo.

Octopus ocellatus, a marine cephalopod distributed in the coast of South Korea, China, Japan and tropical sea, contains high amounts of taurine. In this study, an enzymatic hydrolysate obtained from O. ocellatus meat was evaluated for its antioxidant effects using a human liver cell line and zebrafish embryo model. Enzymatic hydrolysates of the O. ocellatus meat (OOM) were prepared using six different enzymes. Among the enzymatic hydrolysates, Alcalase hydrolysate of OOM (OOMAH) showed the highest scavenging effects against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radicals and hydrogen peroxide (H2O2). Moreover, it showed a high oxygen radical absorbance capacity (ORAC). OOMAH treatment effectively reduced the hydroxyl radical-induced DNA damage. OOMAH reduced the production of reactive oxygen species (ROS) in H2O2-treated hepatocytes without cytotoxicity. Furthermore, OOMAH improved the survival rate and reduced the intracellular ROS levels in H2O2-treated zebrafish embryos. Compositional analysis of amino acids indicated a high content of taurine in OOMAH. Current results suggest that OOMAH possesses antioxidant bioactivities and could provide protective effects against H2O2-induced oxidative stress. Therefore, OOMAH might be used as a potential resource of functional foods.

Anti-inflammatory Effects of Galactose-Taurine Sodium Salt: A Taurine Derivate in Zebrafish In Vivo Model.

Taurine, the plentiful amino acids in mammalian cells exerts various biological activities including antioxidant and anti-inflammatory effects. Inflammation can cause several diseases such as cancer, heart disease, rheumatoid arthritis and immune system reactions. Here, we investigated anti-inflammatory effects of Galactose-Taurine sodium salt (Gal-Tau), a newly synthesized taurine derivate in LPS-stimulated zebrafish embryos in vivo model. The result showed that Gal-Tau improved the survival rate and the edema in LPS-treated zebrafish embryos. Also, Gal-Tau effectively reduced the productions of nitric oxide (NO), reactive oxygen species (ROS) and cell death induced by LPS in zebrafish embryos. In addition, Gal-Tau regulated the expression levels of inflammatory mediators such as inducible NOS (iNOS) and cycloxygenase 2 (COX-2) as well as IL-6 and TNF-α, inflammatory cytokines known as important key mediators of inflammation. Taken together, this study first indicates that Gal-Tau could be considered as an effective anti-inflammatory material with its anti-inflammatory activity.

Xylose-Taurine Reduced Suppresses the Inflammatory Responses in Lipopolysaccharide-Stimulated Raw264.7 Macrophages.

Here, the anti-inflammatory effect of Xylose-Taurine reduced (X-T-R), a taurine derivate was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. X-T-R reduced the generations of nitric oxide (NO) and prostaglandin E2 (PGE2) induced by the stimulation of LPS in RAW 264.7 by suppressing the protein expression of iNOS and COX-2 known as inflammatory mediators. Also, X-R-T reduced the expression levels of the pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF-α). Moreover, X-T-R inhibited the activation of nuclear factor-κB (NF-κB) and the phosphorylation of inhibitor κB (IκB)-α. In conclusion, these results first indicate that X-T-R inhibits LPS-induced inflammation by regulating the NF-κB signal pathway in macrophages.

Protective Effects of Xylose-Taurine Reduced against Damages Caused by Oxidative Stress in Zebrafish Embryos In Vivo Model.

The zebrafish (Danio rerio) is useful and convenient vertebrate models in various studies in human disease and drug discovery. In this present study, we first evaluated whether Xylose-Taurine reduced (X-T-R), a taurine derivate protects zebrafish embryos against oxidative stress caused by AAPH (2,2'-Azobis(2-amidinopropane) dihydrochloride). First of all, we selected the concentration of X-T-R showing no toxicity in zebrafish embryos. We identified that X-T-R significantly increased the survival of zebrafish embryo reduced by treatment of AAPH. Also, X-T-R effectively inhibited the productions of reactive oxygen species (ROS) and nitric oxide (NO) as well as the formation of cell death in zebrafish embryos. Moreover, X-T-R down-regulated the expression levels of Bax, caspase-3, caspase-9 and p53 known as pro-apoptotic molecules, whereas up-regulated those of Bcl-2, an anti-apoptotic molecule in AAPH-treated zebrafish embryos. From these results, this study reveals that X-T-R, a taurine derivate might be a potential protector against various damages caused by oxidative stress.