Fucosterol isolated from Sargassum horneri attenuates allergic responses in immunoglobulin E/bovine serum albumin-stimulated mast cells and passive cutaneous anaphylaxis in mice.

Allergic diseases have become a serious problem worldwide and occur when the immune system overreacts to stimuli. Sargassum horneri is an edible marine brown alga with pharmacological relevance in treating various allergy-related conditions. Therefore, this study aimed to investigate the effect of fucosterol (FST) isolated from S. horneri on immunoglobulin E(IgE)/bovine serum albumin (BSA)-stimulated allergic reactions in mouse bone marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in BALB/c mice. The in silico analysis results revealed the binding site modulatory potential of FST on the IgE and IgE-FcεRI complex. The findings of the study revealed that FST significantly suppressed the degranulation of IgE/BSA-stimulated BMCMCs by inhibiting the release of ß-hexosaminidase and histamine in a dose-dependent manner. In addition, FST effectively decreased the expression of FcεRI on the surface of BMCMCs and its IgE binding. FST dose-dependently downregulated the expression of allergy-related cytokines (interleukin (IL)-4, -5, -6, -13, tumor necrosis factor (TNF)-α, and a chemokine (thymus and activation-regulated chemokine (TARC)) by suppressing the activation of nuclear factor-κB (NF-κB) and Syk-LAT-ERK-Gab2 signaling in IgE/BSA-stimulated BMCMCs. As per the histological analysis results of the in vivo studies with IgE-mediated PCA in BALB/c mice, FST treatment effectively attenuated the PCA reactions. These findings suggest that FST has an immunopharmacological potential as a naturally available bioactive compound for treating allergic reactions.

In vitro and in vivo immuno-enhancing effect of fucoidan isolated from non-edible brown seaweed Sargassum thunbergii.

Fucoidan has been reported to have various biological activities, such as antioxidant, antitumor and anticoagulant, with various health benefits. However, few studies have been conducted to extract fucoidan from Sargassum thunbergii in terms of its immuno-enhancing activities. This aim of this study was to investigate the immuno-enhancing effect of fucoidan (S3) isolated from Sargassum thunbergii through water extraction and ethanol precipitation in RAW 264.7 macrophages and zebrafish. The results showed that S3 contained a relatively high content of fucose and sulfated polysaccharide. Fourier-transform infrared spectroscopy (FTIR) results show that the characteristic peaks at 845 cm-1 and 1220-1270 cm-1 indicate that S3 contains sulfate groups. In vitro, S3 effectively enhanced nitric oxide (NO) production and phagocytic activity. In addition, the results of the study demonstrated that the secretion of tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, and IL-10 was upregulated by nuclear factor kappa B (NF-κB) signaling pathway in a dose-dependent manner. In vivo, S3 activates zebrafish immune responses by promoting secretion of NO and activating the NF-κB pathway. Overall, these results suggest that S3 could be used as a functional ingredient added to nutritional supplements and functional foods.

Peptides inhibiting angiotensin-I-converting enzyme: Isolation from flavourzyme hydrolysate of Protaetia brevitarsis larva protein and identification.

Many angiotensin-I-converting enzyme (ACE) inhibitory peptides are used to prevent and manage hypertension. In this study, ACE inhibitory peptides were isolated from an insect protein that is attracting attention for it potential antihypertensive activity. Protaetia brevitarsis larva protein was enzymatically hydrolyzed by Flavourzyme®, and the hydrolysate was shown to inhibit ACE. Subsequent fractionation, using ultrafiltration and gel permeation chromatography followed by liquid chromatography-tandem mass spectrometry analysis, identified four previously unknown peptides with significant ACE inhibition characteristics (Ser-Tyr, Pro-Phe, Tyr-Pro-Tyr, and Trp-Ile). The highest inhibition activity observed for Trp-Ile. These peptides stimulated production of NO in human umbilical vein endothelial cells and, based on molecular docking analysis, exerted their inhibitory effects via hydrogen bonding with the ACE receptor active site. Thus, the identified peptides can be considered as promising candidates for ACE inhibition and have potential to be used as functional food ingredients.

Ishophloroglucin A Ameliorates VEGF-Induced Epithelial-Mesenchymal Transition via VEGFR2 Pathway Inhibition in Microgravity-Stimulated Human Retinal Pigment Epithelial Cells.

Microgravity stimulation is associated with retinal pigment epithelial (RPE) cells that transition to mesenchymal cells (EMT), and these pathological changes cause visual impairment. Vascular endothelial growth factor (VEGF) is produced from the RPE and contributes to photoreceptor survival. However, changes in VEGF production and function under microgravity stimulation are unknown. In this study, we verified that microgravity stimulation changed the morphological characteristics of human RPE cells (ARPE19 cells) and the expression of actin cytoskeleton regulators, which are related to excessive VEGF expression. Interestingly, microgravity stimulation increased not only the production of VEGF but also the expression of EMT markers. Previously, we studied the potential of ishophloroglucin A (IPA), a phlorotannin, as an antioxidant. In silico results confirmed that IPA could structurally bind to VEGF receptor 2 (VEGFR2) among VEGFRs and inhibit the VEGF pathway. IPA significantly decreased VEGF production and EMT marker expression in microgravity-stimulated cells. It also significantly reduced excessive cell migration in VEGF-induced EMT. Overall, our findings suggested that IPA treatment decreased VEGF production and EMT marker expression in microgravity-stimulated or VEGF-treated ARPE19 cells, and this decrease in EMT could restore excessive cell migration by inhibiting the VEGF/VEGFR2 pathway. Therefore, it is a potential therapeutic candidate for angiogenesis-related eye diseases.

Anti-Melanogenesis and Photoprotective Effects of Ecklonia maxima Extract Containing Dieckol and Eckmaxol.

Seaweeds are potential ingredients in the cosmeceutical industry. Our previous study demonstrates that the phlorotannin-enriched extract of Ecklonia maxima (EME-EA) containing dieckol and eckmaxol possesses strong anti-inflammatory activity and suggests the cosmeceutical potential of EME-EA. In order to evaluate the cosmeceutical potential of EME-EA, the anti-melanogenesis and photoprotective effects of EME-EA were investigated in this study. EME-EA remarkably inhibited mushroom tyrosinase and melanogenesis in alpha-melanocyte-stimulating hormone-stimulated B16F10 cells. In addition, EME-EA significantly suppressed UVB-induced HaCaT cell death that was consistent with inhibition of apoptosis and reduction in scavenging intracellular reactive oxygen species. Furthermore, EME-EA significantly inhibited collagen degradation and matrix metalloproteinases expression in UVB-irradiated HDF cells in a concentration-dependent manner. These results indicate that EME-EA possesses strong anti-melanogenesis and photoprotective activities and suggest EME-EA is an ideal ingredient in the pharmaceutical and cosmeceutical industries.

Isolation and Characterization of Efficient Active Compounds Using High-Performance Centrifugal Partition Chromatography (CPC) from Anti-Inflammatory Activity Fraction of Ecklonia maxima in South Africa.

Ecklonia maxima is a brown seaweed, which is abundantly distributed in South Africa. This study investigated an efficient approach using high-performance centrifugal partition chromatography (HPCPC), which has been successfully developed for the isolation and purification of phlorotannins, eckmaxol, and dieckol from the ethyl acetate fraction of E. maxima (EEM). We evaluated EEM for its inhibitory effect against lipopolysaccharide (LPS)-induced inflammatory responses in zebrafish embryos. The separation of eckmaxol and dieckol from samples of EEM using HPCPC was found to be of high purity and yield under an optimal solvent system composed of n-hexane:ethyl acetate:methanol:water (2:7:3:7, v/v/v/v). To evaluate the anti-inflammatory efficacy of EEM containing active compounds, zebrafish embryos exposed to LPS were compared with and without EEM treatment for nitric oxide (NO) production, reactive oxygen species (ROS) generation, and cell death two days after fertilization. These evaluations indicate that EEM alleviated inflammation by inhibiting cell death, ROS, and NO generation induced by LPS treatment. According to these results, eckmaxol and dieckol isolated from brown seaweed E. maxima could be considered effective anti-inflammatory agents as pharmaceutical and functional food ingredients.

Structural characteristics of sulfated polysaccharides from Sargassum horneri and immune-enhancing activity of polysaccharides combined with lactic acid bacteria.

Sargassum horneri (SH), a marine brown alga, is known to contain a variety of bioactive ingredients and previous studies reported sulfated polysaccharides in SH as a potential candidate for a functional ingredient. However, immune-enhancing activity combined with Lactobacillus plantarum (LAB) is not yet studied. In the present study, we attempted to characterize sulfated polysaccharides (SHCPs) in SH by MALDI-TOF/TOF mass spectrometry and evaluate their immune-enhancing effect on macrophage cells. The main residue of SHCPs in SH is 2-sulfated 1,4-linked L-fucose and this epitope combined with LAB shows immune enhancement properties through cytokine production at the cellular level and increases the population of lymphocytes and myelomonocytes in the adult zebrafish kidney. These results indicate that SHCPs, along with LAB, have potent immune-enhancing activity and may be utilized as a potential immunomodulatory ingredient.

Antihypertensive Effects of IGTGIPGIW Peptide Purified from Hippocampus abdominalis: p-eNOS and p-AKT Stimulation in EA.hy926 Cells and Lowering of Blood Pressure in SHR Model.

The aim of this study was to assess the potential hypertensive effects of the IGTGIPGIW peptide purified from Hippocampus abdominalis alcalase hydrolysate (HA) for application in the functional food industry. We investigated the antihypertensive effects of IGTGIPGIW in vitro by assessing nitric oxide production in EA.hy926 endothelial cells, which is a major factor affecting vasorelaxation. The potential vasorelaxation effect was evaluated using 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, a fluorescent stain. IGTGIPGIW significantly increased the expression of endothelial-derived relaxing factors, including endothelial nitric oxide synthase and protein kinase B, in EA.hy926 cells. Furthermore, oral administration of IGTGIPGIW significantly lowered the systolic blood pressure (183.60 ± 1.34 mmHg) and rapidly recovered the diastolic blood pressure (143.50 ± 5.55 mmHg) in the spontaneously hypertensive rat model in vivo. Our results demonstrate the antihypertensive activity of the IGTGIPGIW peptide purified from H. abdominalis and indicate its suitability for application in the functional food industry.

Therapeutic Potential of Phlorotannin-Rich Ecklonia cava Extract on Methylglyoxal-Induced Diabetic Nephropathy in In Vitro Model.

Advanced glycation end-products (AGEs) play a vital role in the pathogenesis of diabetic complications. Methylglyoxal (MGO), one of the major precursors of AGEs, is a highly reactive dicarbonyl compound that plays an important role in the pathogenesis of diabetic nephropathy. This study was designed to evaluate the therapeutic potential of phlorotannin-rich Ecklonia cava extract (ECE) on MGO-induced diabetic nephropathy in in vitro models using mouse glomerular mesangial cells. ECE showed anti-glycation activity via breaking of AGEs-collagen cross-links and inhibition of AGEs formation and AGE-collagen cross-linking formation. The renoprotective effects were determined by assessing intracellular reactive oxygen species (ROS) and MGO accumulation, cell apoptosis, and the Nrf-2/ARE signaling pathway. MGO-induced renal damage, intracellular ROS production level, and MGO-protein adduct accumulation were significantly decreased by pretreating ECE. Moreover, ECE pretreatment exhibited preventive properties against MGO-induced dicarbonyl stress via activation of the Nrf2/ARE signaling pathway and reduction of RAGE protein expression in mouse glomerular mesangial cells. Collectively, these results indicated potential anti-glycation properties and prominent preventive effects of ECE against MGO-induced renal damage. Additionally, ECE may be utilized for the management of AGE-related diabetic nephropathy.

Anti-Inflammatory Effect of Sulfated Polysaccharides Isolated from Codium fragile In Vitro in RAW 264.7 Macrophages and In Vivo in Zebrafish.

In this study, the anti-inflammatory activity of sulfated polysaccharides isolated from the green seaweed Codium fragile (CFCE-PS) was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results demonstrated that CFCE-PS significantly increased the viability of LPS-induced RAW 264.7 cells in a concentration-dependent manner. CFCE-PS remarkably and concentration-dependently reduced the levels of inflammatory molecules including prostaglandin E2, nitric oxide (NO), interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6 in LPS-stimulated RAW 264.7 cells. In addition, in vivo test results indicated that CFCE-PS effectively reduced reactive oxygen species, cell death, and NO levels in LPS-stimulated zebrafish. Thus, these results indicate that CFCE-PS possesses in vitro and in vivo anti-inflammatory activities and suggest it is a potential ingredient in the functional food and pharmaceutical industries.

Mitigative Effects of PFF-A Isolated from Ecklonia cava on Pigmentation in a Zebrafish Model and Melanogenesis in B16F10 Cells.

Melanin synthesis is a defense mechanism that prevents skin damage, but excessive accumulation of melanin occurs in the skin in various reactions such as pigmentation, lentigines, and freckles. Although anti-melanogenic effects have been demonstrated for various naturally occurring marine products that inhibit and control tyrosinase activity, most studies have not been extended to in vivo applications. Phlorofucofuroeckol-A (PFF-A, 12.5-100 µM) isolated from Ecklonia cava has previously been shown to have tyrosinase-mitigative effects in B16F10 cells, but it has not been evaluated in an in vivo model, and its underlying mechanism for anti-melanogenic effects has not been studied. In the present study, we evaluated the safety and efficacy of PFF-A for anti-melanogenic effects in an in vivo model. We selected low doses of PFF-A (1.5-15 nM) and investigated their mitigative effects on pigmentation stimulated by α-MSH in vivo and their related-mechanism in an in vitro model. The findings suggest that low-dose PFF-A derived from E. cava suppresses pigmentation in vivo and melanogenesis in vitro. Therefore, this study presents the possibility that PFF-A could be utilized as a new anti-melanogenic agent in the cosmeceutical industries.

Detrimental impact of fine dust on zebrafish: Investigating a protective agent against ocular-damage using in vitro and in vivo models.

Pollution caused by fine dust is becoming a global problem in the aquatic environment. Many studies have investigated the hazards that fine dust may pose to terrestrial organisms; however, information on the effects on aquatic environments remain limited. In this study, the physicochemical characteristics of the fine dust associated with the captured powder or liquid state were compared using scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDS). Raw fine dust (RFD), in the captured powder state, was suspended in water (SFD), and the elemental composition, morphology, and size distribution of both were analyzed. Zebrafish were used as a model to study the effects of SFD-exposure on aquatic organisms. A fatal malformation was observed in the integuments of zebrafish exposed to SFD, specifically in the exterior and interior eye tissues. Furthermore, the exposure of SFD to Tg (flk; EGFP) zebrafish remarkably increased ocular vessel diameter expansion along with blood flow velocity. Regarding vessel diameter expansion, EA.hy926 cells exposed to SFD were adversely affected, with a significant increase in cell migration and capillary-like structure formation, which are angiogenic markers. The SFD-induced angiogenesis in vitro and in vivo was dramatically restored to normal via α/ß-adenosine isolated from the anti-angiogenic brown algae Ishige okamurae extract. Taken together, the current study presents solid evidence of the altered physicochemical characteristics of SFD compared to RFD, and the detrimental impact of SFD in an aquatic in vivo zebrafish model. In addition, the protective effect of α/ß-adenosine, a marine natural product, on SFD-induced angiogenesis suggests that it can be used as an agent to reduce the adverse effects of SFD on aquatic animals.

Arsenic removal from the popular edible seaweed Sargassum fusiforme by sequential processing involving hot water, citric acid, and fermentation.

Higher quantities of arsenic (As) in Sargassum fusiforme limit its use as a food ingredient. The present study aimed to reduce As in S. fusiforme using sequential processing involving hot water, citric acid, and fermentation. The As content in S. fusiforme of 76.18 mg/kg was reduced to 30.47 mg/kg and 24.45 mg/kg using hot water and citric acid processing, respectively. However, the As content in S. fusiforme was reduced to 9.09 mg/kg by sequential processing with hot water and citric acid. Using response surface methodology, optimal processing conditions for S. fusiforme were determined to be treatment with hot water at 60 °C for 120 min followed by treatment with 0.4% citric acid. To further reduce the As content, the processed S. fusiforme was fermented by Lactobacillus rhamnosus, and the As content was further reduced to 1.64 mg/kg. In addition, the levels of organic acids and amino acids in S. fusiforme pre- and post-fermentation were significantly altered. These results indicated that the As content in S. fusiforme could be effectively reduced using the sequential processing with hot water, citric acid, and L. rhamnosus fermentation, and the organic acid and amino acid levels were significantly altered by L. rhamnosus fermentation.

In Vitro and In Vivo Photoprotective Effects of (-)-Loliode Isolated from the Brown Seaweed, Sargassum horneri.

Skin is the largest organ of humans. Overexposure to ultraviolet (UV) is the primary environmental factor that causes skin damage. The compound, (-)-loliode, isolated from the brown seaweed Sargassum horneri, showed strong antioxidant and anti-inflammatory activities in in vitro and in vivo models. To further explore the potential of (-)-loliode in cosmetics, in the present study, we investigated the photoprotective effect of (-)-loliode in vitro in skin cells and in vivo in zebrafish. The results indicated that (-)-loliode significantly reduced intracellular reactive oxygen species (ROS) level, improved cell viability, and suppressed apoptosis of UVB-irradiated human keratinocytes. In addition, (-)-loliode remarkably attenuated oxidative damage, improved collagen synthesis, and inhibited matrix metalloproteinases expression in UVB-irradiated human dermal fibroblasts. Furthermore, the in vivo test demonstrated that (-)-loliode effectively and dose-dependently suppressed UVB-induced zebrafish damage displayed in decreasing the levels of ROS, nitric oxide, lipid peroxidation, and cell death in UVB-irradiated zebrafish. These results indicate that (-)-loliode possesses strong photoprotective activities and suggest (-)-loliode may an ideal ingredient in the pharmaceutical and cosmeceutical industries.

Zebrafish Model for Studying Dexamethasone-Induced Muscle Atrophy and Preventive Effect of Maca (Lepidium meyenii).

Loss of myofibers during muscle atrophy affects functional capacity and quality of life. Dexamethasone, an inducer of rapid atrophy of skeletal myofibers, has been studied as a glucocorticoid receptor in muscle atrophy or motor neurodegeneration. In this study, we examined dexamethasone-induced muscle atrophy using zebrafish (Danio rerio), a vertebrate model, and assessed whether administration of Lepidium meyenii (maca) as a dietary supplement can prevent muscle atrophy. Changes in skeletal myofibers in zebrafish were evaluated after exposure to dexamethasone for different periods and at different concentrations. Under optimized conditions, zebrafish pre-fed with maca for 3 days were exposed to 0.01% dexamethasone for 1 h/day for 7 days. Thereafter, myofiber loss, damaged muscle contractile proteins, and abnormal exploratory behavior due to the structural and functional impairment of skeletal muscle associated with muscle atrophy were investigated using hematoxylin-eosin, immunofluorescence staining, and behavioral analyses. Our findings suggest that dexamethasone induces muscle atrophy in zebrafish, inhibiting exploratory behavior by inducing myofiber loss, inhibiting muscle contraction, and causing changes in endurance and velocity. Thus, the zebrafish model can be used to screen pharmaceutical agents and to study muscle atrophy. Furthermore, maca is a potential dietary supplement to prevent muscle atrophy, as it protects muscle fibers.

Purification and Structural Characterization of Sulfated Polysaccharides Derived from Brown Algae, Sargassum binderi: Inhibitory Mechanism of iNOS and COX-2 Pathway Interaction.

Among the components derived from brown algae, anionic sulfated polysaccharides, which contain sulfated fucose as the major monosaccharide, exert significant biological activities. In this study, we purified and structurally characterized sulfated polysaccharides from brown algae, Sargassum binderi (S. binderi; SBPs), and evaluated their biological activity in vitro and in vivo. The SBPs were separated based on their charges and their biophysical properties were investigated according to their functional groups, structural features, and molecular weights using FTIR, NMR, and MALS. Among all the SBPs, Fraction 4 (SBP-F4), with an average molecular weight of 2.867 × 105 g/mol, had the highest polysaccharide and sulfate contents (75.15 ± 0.25% and 24.08 ± 0.18%, respectively). The biological activities of SBP-F4 were investigated further in vitro and in vivo. Our results showed that SBP-F4 significantly suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in LPS-activated macrophages. Moreover, in the LPS-treated zebrafish model, a significant decrease in cell death and NO production was observed. Collectively, these results show that SBPs not only exert protective effects against LPS-induced cytotoxicity but also inhibit the activation and anti-inflammatory activity of macrophages. Therefore, polysaccharides derived from S. binderi are potential anti-inflammatory agents for use in clinical settings.

(-)-Loliolide Isolated from Sargassum horneri Suppressed Oxidative Stress and Inflammation by Activating Nrf2/HO-1 Signaling in IFN-γ/TNF-α-Stimulated HaCaT Keratinocytes.

The present study evaluated the effects of (-)-loliolide isolated from Sargassum horneri (S. horneri) against oxidative stress and inflammation, and its biological mechanism in interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocytes. The results showed that (-)-loliolide improved the cell viability by reducing the production of intracellular reactive oxygen species (ROS) in IFN-γ/TNF-α-stimulated HaCaT keratinocytes. In addition, (-)-loliolide effectively decreased the expression of inflammatory cytokines (interleukin (IL)-4 IL-6, IL-13, IFN-γ and TNF-α) and chemokines (CCL11 (Eotaxin), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC)), by downregulating the expression of epidermal-derived initial cytokines (IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)). Furthermore, (-)-loliolide suppressed the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling, whereas it activated nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Interestingly, the cytoprotective effects of (-)-loliolide against IFN-γ/TNF-α stimulation were significantly blocked upon inhibition of HO-1. Taken together, these results suggest that (-)-loliolide effectively suppressed the oxidative stress and inflammation by activating the Nrf2/HO-1 signaling in IFN-γ/TNF-α-stimulated HaCaT keratinocytes.

Ecklonia cava Extract and Its Derivative Dieckol Promote Vasodilation by Modulating Calcium Signaling and PI3K/AKT/eNOS Pathway in In Vitro and In Vivo Models.

Nitric oxide (NO), an endothelial-derived relaxing factor synthesized by endothelial nitric oxide synthase (eNOS) in endothelial cells, enhances vasodilation by modulating vascular tone. The calcium concentration critically influences eNOS activation in endothelial cells. Thus, modulation of calcium-dependent signaling pathways may be a potential therapeutic strategy to enhance vasodilation. Marine algae reportedly possess protective effects against cardiovascular disorders, including hypertension and vascular dysfunction; however, the underlying molecular signaling pathways remain elusive. In the present study, we extracted and isolated dieckol from Ecklonia cava and investigated calcium transit-enhanced vasodilation. Calcium modulation via the well-known M3 muscarinic acetylcholine receptor (AchM3R), which is linked to NO formation, was investigated and the vasodilatory effect of dieckol was verified. Our results indicated that dieckol effectively promoted NO generation via the PI3K/Akt/eNOS axis and calcium transients influenced by AchM3R. We also treated Tg(flk: EGFP) transgenic zebrafish with dieckol to assess its vasodilatory effect. Dieckol promoted vasodilation by enlarging the dorsal aorta diameter, thus regulating blood flow velocity. In conclusion, our findings suggest that dieckol modulates calcium transit through AchM3R, increases endothelial-dependent NO production, and efficiently enhances vasodilation. Thus, E. cava and its derivative, dieckol, can be considered as potential natural vasodilators.

Phloroglucinol and dieckol isolated from Ecklonia cava suppress impaired diabetic angiogenesis; A study of in-vitro and in-vivo.

Abnormalities in angiogenesis that are associated with diabetes may contribute to vascular complications and result in disabilities and death. Furthermore, an imbalance in angiogenesis in different tissues, including the retina and kidney, can play a role in the pathogenesis of diabetic microvascular complications. Phlorotannins, such as phloroglucinol (PG) and dieckol (DK), which are found in Ecklonia cava exhibit antioxidant and anti-inflammatory activities that improve endothelial function in hypertension. However, reports on the effects of these compounds on diabetes-induced angiogenesis in vivo and in vitro are scarce. In this study, we assessed the antiangiogenic effects of PG and DK on endothelial cells treated with a high concentration of glucose to mimic angiogenesis. In addition, we sought to determine the effects of these compounds on cell proliferation, cell migration, and capillary formation. In silico docking of PG and DK into VEGFR-2 revealed their potential as therapeutic agents against angiogenesis. Further, both compounds were identified to inhibit the formation of the retinal vessel in transgenic zebrafish (flk:EGFP) embryos under high glucose conditions. These findings suggested that PG and DK derived from E. cava are potential inhibitors of angiogenesis in diabetic vascular complications and could, therefore, be used to develop angiogenic agents.