Investigation of Physical Characteristics and In Vitro Anti-Inflammatory Effects of Fucoidan from Padina arborescens: A Comprehensive Assessment against Lipopolysaccharide-Induced Inflammation.

A biocompatible, heterogeneous, fucose-rich, sulfated polysaccharide (fucoidan) is biosynthesized in brown seaweed. In this study, fucoidan was isolated from Padina arborescens (PAC) using celluclast-assisted extraction, purified, and evaluated for its anti-inflammatory potential in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Structural analyses were performed using Fourier transform infrared (FTIR) and scanning electron microscopy. Among the purified fucoidans, fucoidan fraction 5 (F5) exhibited strong inhibitory activity against LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine generation through the regulation of iNOS/COX-2, MAPK, and NF-κB signaling in LPS-induced RAW 264.7 cells. Determination of the structural characteristics indicated that purified F5 exhibited characteristics similar to those of commercial fucoidan. In addition, further analyses suggested that F5 inhibits LPS-induced toxicity, cell death, and NO generation in zebrafish models. Taken together, these findings imply that P. arborescens fucoidans have exceptional anti-inflammatory action, both in vitro and in vivo, and that they may have prospective uses in the functional food sector.

Narirutin-Rich Celluclast Extract from Mandarin (Citrus unshiu) Peel Alleviates High-Fat Diet-Induced Obesity and Promotes Energy Metabolism in C57BL/6 Mice.

Mandarin peel, a main by-product from the processing of citrus juice, has been highlighted for its various bioactivities and functional ingredients. Our previous study proved the inhibitory effects of Celluclast extract from mandarin peel (MPCE) on lipid accumulation and differentiation in 3T3-L1 adipocytes. Therefore, the current study aimed to evaluate the anti-obesity effect of MPCE in high-fat diet (HFD)-induced obese mice. The high-performance liquid chromatography (HPLC) analysis exhibited that narirutin and hesperidin are the main active components of MPCE. Our current results showed that MPCE supplementation decreased adiposity by reducing body and organ weights in HFD-induced obese mice. MPCE also reduced triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and leptin contents in the serum of HFD-fed mice. Moreover, MPCE significantly inhibited hepatic lipid accumulation by regulating the expression levels of proteins associated with lipid metabolism, including sterol regulatory element-binding protein (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Furthermore, MPCE administration significantly inhibited both adipogenesis and lipogenesis, with modulation of energy metabolism by activating 5' adenosine monophosphate-activated protein kinase (AMPK) and lipolytic enzymes such as hormone-sensitive lipase (HSL) in the white adipose tissue (WAT). Altogether, our findings indicate that MPCE improves HFD-induced obesity and can be used as a curative agent in pharmaceuticals and nutraceuticals to alleviate obesity and related disorders.

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.

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.

Diphlorethohydroxycarmalol inhibits melanogenesis via protein kinase A/cAMP response element-binding protein and extracellular signal-regulated kinase-mediated microphthalmia-associated transcription factor downregulation in α-melanocyte stimulating hormone-stimulated B16F10 melanoma cells and zebrafish.

Diphlorethohydroxycarmalol (DPHC) is a marine polyphenolic compound derived from brown alga Ishige okamurae. A previously study has suggested that DPHC possesses strong mushroom tyrosinase inhibitory activity. However, the anti-melanogenesis effect of DPHC has not been reported at cellular level. The objective of the present study was to clarify the melanogenesis inhibitory effect of DPHC and its molecular mechanisms in murine melanoma cells (B16F10) and zebrafish model. DPHC significantly inhibited tyrosinase activity and melanin content dose-dependently in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. This polyphenolic compound also suppressed the expression of phosphorylation of cAMP response element-binding protein (CREB) by attenuating phosphorylation of cAMP-dependent protein kinase A, resulting in decreased MITF expression levels. Furthermore, DPHC downregulated MITF protein expression levels by promoting the phosphorylation of extracellular signal-regulated kinase. It also inhibited tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH stimulated B16F10 cells. In in vivo studies using zebrafish, DPHC also markedly inhibited melanin synthesis in a dose-dependent manner. These results demonstrate that DPHC can effectively inhibit melanogenesis in melanoma cells in vitro and in zebrafish in vivo, suggesting that DPHC could be applied in fields of pharmaceutical and cosmeceuticals as a skin-whitening agent. Significance of study: The present study showed for the first time that DPHC could inhibit a-MSH-stimulated melanogenesis via PKA/CREB and ERK pathway in melanoma cells. It also could inhibit pigmentation in vivo in a zebrafish model. This evidence suggests that DPHC has potential as a skin whitening agent. Taken together, DPHC could be considered as a novel anti-melanogenic agent to be applied in cosmetic, food, and medical industry.

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.

Effects of Ethanol Extracts from Grateloupia elliptica, a Red Seaweed, and Its Chlorophyll Derivative on 3T3-L1 Adipocytes: Suppression of Lipid Accumulation through Downregulation of Adipogenic Protein Expression.

Grateloupia elliptica (G. elliptica) is a red seaweed with antioxidant, antidiabetic, anticancer, anti-inflammatory, and anticoagulant activities. However, the anti-obesity activity of G. elliptica has not been fully investigated. Therefore, the effect of G. elliptica ethanol extract on the suppression of intracellular lipid accumulation in 3T3-L1 cells by Oil Red O staining (ORO) was evaluated. Among the eight red seaweeds tested, G. elliptica 60% ethanol extract (GEE) exhibited the highest inhibition of lipid accumulation. GEE was the only extract to successfully suppress lipid accumulation among ethanol extracts from eight red seaweeds. In this study, we successfully isolated chlorophyll derivative (CD) from the ethyl acetate fraction (EA) of GEE by high-performance liquid chromatography and evaluated their inhibitory effect on intracellular lipid accumulation in 3T3-L1 adipocytes. CD significantly suppressed intracellular lipid accumulation. In addition, CD suppressed adipogenic protein expression such as sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid binding protein 4 (FABP4). Taken together, our results indicate that CD from GEE inhibits lipid accumulation by suppressing adipogenesis via the downregulation of adipogenic protein expressions in the differentiated adipocytes. Therefore, chlorophyll from G. elliptica has a beneficial effect on lipid metabolism and it could be utilized as a potential therapeutic agent for preventing obesity.

Protocatechuic Aldehyde Inhibits α-MSH-Induced Melanogenesis in B16F10 Melanoma Cells via PKA/CREB-Associated MITF Downregulation.

Protocatechuic aldehyde (PA) is a naturally occurring phenolic compound that is a potent inhibitor of mushroom tyrosinase. However, the molecular mechanisms of the anti-melanogenesis activity of PA have not yet been reported. The aim of the current study was to clarify the melanogenesis inhibitory effects of PA and its molecular mechanisms in murine melanoma cells (B16F10). We first predicted the 3D structure of tyrosinase and used a molecular docking algorithm to simulate binding between tyrosinase and PA. These molecular modeling studies calculated a binding energy of -527.42 kcal/mol and indicated that PA interacts with Cu400 and 401, Val283, and His263. Furthermore, PA significantly decreased α-MSH-induced intracellular tyrosinase activity and melanin content in a dose-dependent manner. PA also inhibited key melanogenic proteins such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH-stimulated B16F10 cells. In addition, PA decreased MITF expression levels by inhibiting phosphorylation of cAMP response element-binding protein (CREB) and cAMP-dependent protein kinase A (PKA). These results demonstrate that PA can effectively suppress melanin synthesis in melanoma cells. Taken together, our results show that PA could serve as a potential inhibitor of melanogenesis, and hence could be explored as a possible skin-lightening agent.

Protocatechuic Aldehyde Attenuates UVA-Induced Photoaging in Human Dermal Fibroblast Cells by Suppressing MAPKs/AP-1 and NF-κB Signaling Pathways.

Ultraviolet radiation (UV) is a major causative factor of DNA damage, inflammatory responses, reactive oxygen species (ROS) generation and a turnover of various cutaneous lesions resulting in skin photoaging. The purpose of this study is to investigate the protective effect of protocatechuic aldehyde (PA), which is a nature-derived compound, against UVA-induced photoaging by using human dermal fibroblast (HDF) cells. In this study, our results indicated that PA significantly reduced the levels of intracellular ROS, nitric oxide (NO), and prostaglandins-E2 (PGE2) in UVA-irradiated HDF cells. It also inhibited the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Besides, PA significantly suppressed the expression of matrix metalloproteinases-1 (MMP-1) and pro-inflammatory cytokines and promoted collagen synthesis in the UVA-irradiated HDF cells. These events occurred through the regulation of activator protein 1 (AP-1), nuclear factor-κB (NF-κB), and p38 signaling pathways in UVA-irradiated HDF cells. Our findings suggest that PA enhances the protective effect of UVA-irradiated photoaging, which is associated with ROS scavenging, anti-wrinkle, and anti-inflammatory activities. Therefore, PA can be a potential candidate for the provision of a protective effect against UVA-stimulated photoaging in the pharmaceutical and cosmeceutical industries.

Inhibition of Adipogenesis by Diphlorethohydroxycarmalol (DPHC) through AMPK Activation in Adipocytes.

The purpose of this study was to investigate the antiobesity effect and the mechanism of action of diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae in 3T3-L1 cells. The antiobesity effects were examined by evaluating intracellular fat accumulation in Oil Red O-stained adipocytes. Based on the results, DPHC dose-dependently inhibited the lipid accumulation in 3T3-L1 adipocytes. DPHC significantly inhibited adipocyte-specific proteins such as SREBP-1c, PPARγ, C/EBP α, and adiponectin, as well as adipogenic enzymes, including perilipin, FAS, FABP4, and leptin in adipocytes. These results indicated that DPHC primarily acts by regulating adipogenic-specific proteins through inhibiting fat accumulation and fatty acid synthesis in adipocytes. DPHC treatment significantly increased both AMPK and ACC phosphorylation in adipocytes. These results indicate that DPHC inhibits the fat accumulation by activating AMPK and ACC in 3T3-L1 cells. Taken together, these results suggest that DPHC can be used as a potential therapeutic agent against obesity.

Anti-Obesity Effect of Diphlorethohydroxycarmalol Isolated from Brown Alga Ishige okamurae in High-Fat Diet-Induced Obese Mice.

Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current study explored the effect of DPHC on high-fat diet (HFD)-induced obesity in C57BL/6J mice. The results indicated that oral administration of DPHC (25 and 50 mg/kg/day for six weeks) significantly and dose-dependently reduced HFD-induced adiposity and body weight gain. DPHC not only decreased the levels of triglyceride, low-density lipoprotein cholesterol, leptin, and aspartate transaminase but also increased the level of high-density lipoprotein cholesterol in the serum of HFD mice. In addition, DPHC significantly reduced hepatic lipid accumulation by reduction of expression levels of the critical enzymes for lipogenesis including SREBP-1c, FABP4, and FAS. Furthermore, DPHC remarkably reduced the adipocyte size, as well as decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes including PPARγ, C/EBPα, SREBP-1c, FABP4, and FAS, which regulate the lipid metabolism in the epididymal adipose tissue (EAT). Further studies demonstrated that DPHC significantly stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in both liver and EAT. These results demonstrated that DPHC effectively prevented HFD-induced obesity and suggested that DPHC could be used as a potential therapeutic agent for attenuating obesity and obesity-related diseases.

Bromophenol (5-bromo-3,4-dihydroxybenzaldehyde) isolated from red alga Polysiphonia morrowii inhibits adipogenesis by regulating expression of adipogenic transcription factors and AMP-activated protein kinase activation in 3T3-L1 adipocytes.

The aim of the present study was to investigate the effect of 5-bromo-3,4-dihydroxybenzaldehyde (BD) isolated from Polysiphonia morrowii on adipogenesis and differentiation of 3T3-L1 preadipocytes into mature adipocytes and its possible mechanism of action. Levels of lipid accumulation and triglyceride were significantly lower in BD treated cells than those in untreated cells. In addition, BD treatment reduced protein expression levels of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding proteins α, and sterol regulatory element-binding protein 1 compared with control (no treatment). It also reduced expression levels of adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. AMP-activated protein kinase activation was found to be one specific mechanism involved in the effect of BD. These results demonstrate that BD possesses inhibitory effect on adipogenesis through activating AMP-activated protein kinase signal pathway.

Protective Effects of Novel Antioxidant Peptide Purified from Alcalase Hydrolysate of Velvet Antler Against Oxidative Stress in Chang Liver Cells in Vitro and in a Zebrafish Model In Vivo.

Velvet antler has a long history in traditional medicine. It is also an important healthy ingredient in food as it is rich in protein. However, there has been no report about antioxidant peptides extracted from velvet antler by enzymatic hydrolysis. Thus, the objective of this study was to hydrolyze velvet antler using different commercial proteases (Acalase, Neutrase, trypsin, pepsin, and α-chymotrypsin). Antioxidant activities of different hydrolysates were investigated using peroxyl radical scavenging assay by electron spin resonance spectrometry. Among all enzymatic hydrolysates, Alcalase hydrolysate exhibited the highest peroxyl radical scavenging activity. Alcalase hydrolysate was then purified using ultrafiltration, gel filtration, and reverse-phase high performance liquid chromatography. The purified peptide was identified to be Trp-Asp-Val-Lys (tetrapeptide) with molecular weight of 547.29 Da by Q-TOF ESI mass spectroscopy. This purified peptide exhibited strong scavenging activity against peroxyl radical (IC50 value, 0.028 mg/mL). In addition, this tetrapeptide showed significant protection ability against AAPH-induced oxidative stress by inhibiting of reactive oxygen species (ROS) generation in Chang liver cells in vitro and in a zebrafish model in vivo. This research suggests that the tetrapeptide derived from Alcalase-proteolytic hydrolysate of velvet antler are excellent antioxidants and could be effectively applied as functional food ingredients and pharmaceuticals.

Soft Coral Dendronephthya puetteri Extract Ameliorates Inflammations by Suppressing Inflammatory Mediators and Oxidative Stress in LPS-Stimulated Zebrafish.

Marine-derived extract and/or bioactive compounds have attracted increasing demand due to their unique and potential uses as cures for various inflammation-based diseases. Several studies revealed anti-inflammatory candidates found in soft corals. However, the effects of soft corals on inflammation in an in vivo model remain to be determined. Therefore, the extract of soft coral Dendronephthya puetteri (DPE) was investigated for an in vivo anti-inflammatory effect in a lipopolysaccharide (LPS)-stimulated zebrafish model to determine its potential use as a natural anti-inflammatory agent. We also investigated whether DPE has toxic effects in a zebrafish model. No significant changes were observed in terms of survival, heart beat rate, or developmental abnormalities in the zebrafish embryos exposed to a concentration below 100 µg/mL of DPE. Treating the zebrafish model with LPS-treatment significantly increased the ROS, NO generation, and cell death. However, DPE inhibited this LPS-stimulated ROS, NO generation, and cell death in a dose-dependent manner. In addition, DPE significantly reduced the mRNA expression of both iNOS and COX-2 and markedly suppressed the expression levels of the proinflammatory cytokines, TNF-α and IL-6, in an LPS-stimulated zebrafish model. These findings demonstrate that DPE has profound anti-inflammatory effect in vivo, suggesting that DPE might be a strong natural anti-inflammatory agent.

Mussel (Mytilus coruscus) Water Extract Containing Taurine Prevents LPS-Induced Inflammatory Responses in Zebrafish Model.

Mussel (Mytilus coruscus) water extract had strong anti-inflammatory activities, but the effects and its mechanisms of mussel on anti-inflammatory properties in vivo remain to be determined. This study, therefore, was designed to investigate anti-inflammatory activities of mussel water extract containing a large amounts of taurine (151.96 nmol/mg) using the lipopolysaccharide (LPS)-induced inflammatory zebrafish model. In this study, mussel water extract containing taurine shows potent protective effects against the cell death stimulated by LPS exposure in zebrafish embryos. In addition, zebrafish subjected to LPS treatment exhibited significantly increased reactive oxygen species (ROS) and nitric oxide (NO) levels. However, mussel water extract markedly suppressed LPS-induced ROS and NO production. Our results indicate that mussel water extract attenuated inflammation by inhibiting the LPS-induced intracellular ROS and NO production in zebrafish embryos. These findings could demonstrate the anti-inflammatory activity of mussel water extract containing taurine, which might have a protective effects on inflammatory diseases.

Antioxidant Effects of Short-Neck Clam (Tapes philippinarum) Water Extract Containing Taurine Against AAPH-Induced Oxidative Stress in Zebrafish Embryos.

The purpose of this study was to investigate the antioxidant activities of short-neck clam water extract (SNC-WE) enriched in taurine. In the present study, the half-maximal inhibitory concentration (IC50) values of the SNC-WE for DPPH, superoxide, and alkyl radical scavenging activities determined by an electron spin resonance (ESR) spectrometer were 3.16, 1.54 and 0.58 mg/mL, respectively. Furthermore, we evaluated the inhibitory effect of taurine enriched SNC-WE against the oxidative stress induced by 2,2'-azobis dihydrochloride (AAPH) in zebrafish embryos. In the present study, we observed that taurine enriched SNC-WE significantly suppressed reactive oxygen species (ROS) production, lipid peroxidation as well as cell death in the zebrafish model. These results indicate that taurine enriched SNC-WE might have antioxidant effects in both in vitro and in vivo zebrafish model.

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.

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.

Indole Derivatives Isolated from Brown Alga Sargassum thunbergii Inhibit Adipogenesis through AMPK Activation in 3T3-L1 Preadipocytes.

Seaweed, a popular and abundant food ingredient mainly consumed in Asian countries, is a good source of bioactive compounds with anti-obesity effects. However, the anti-obesity effects of Sargassum thunbergii have not yet been established. In this study, we isolated six indole derivatives (STCs)-indole-2-carboxaldehyde (STC-1), indole-3-carboxaldehyde (STC-2), indole-4-carboxaldehyde (STC-3), indole-5-carboxaldehyde (STC-4), indole-6-carboxaldehyde (STC-5), and indole-7-carboxaldehyde (STC-6)-from S. thunbergii and evaluated their inhibitory effects on adipocyte differentiation in 3T3-L1 cells. We found that STC-1 and STC-5 resulted in non-toxic inhibition of the differentiation of 3T3-L1 adipocytes and thus selected these compounds for further study. STC-1 and STC-5 significantly inhibited lipid accumulation and downregulated the expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1c (SREBP-1c) in a dose-dependent manner. The specific mechanism mediating the effects of STC-1 and STC-5 was shown to be AMP-activated protein kinase (AMPK) activation. Our results demonstrated the inhibitory effect of STC-1 and STC-5 on adipogenesis through the activation of the AMPK signal pathway. Together, these findings suggested that STC-1 and STC-5 may be effective candidates for the prevention of obesity or obesity-related diseases.

Tuberatolide B Suppresses Cancer Progression by Promoting ROS-Mediated Inhibition of STAT3 Signaling.

Tuberatolide B (TTB, C27H34O4) is a diastereomeric meroterpenoid isolated from the Korean marine algae Sargassum macrocarpum. However, the anticancer effects of TTB remain unknown. In this study, we demonstrate that TTB inhibits tumor growth in breast, lung, colon, prostate, and cervical cancer cells. To examine the mechanism by which TTB suppresses cell growth, we determined the effect of TTB on apoptosis, ROS generation, DNA damage, and signal transduction. TTB induced ROS production in MDA-MB-231, A549, and HCT116 cells. Moreover, TTB enhanced DNA damage by inducing γH2AX foci formation and the phosphorylation of DNA damage-related proteins such as Chk2 and H2AX. Furthermore, TTB selectively inhibited STAT3 activation, which resulted in a reduction in cyclin D1, MMP-9, survivin, VEGF, and IL-6. In addition, TTB-induced ROS generation caused STAT3 inhibition, DNA damage, and apoptotic cell death. Therefore, TTB suppresses cancer progression by promoting ROS-mediated inhibition of STAT3 signaling, suggesting that TTB is useful for the treatment of cancer.