dieckol and eckol

Both amyloid-β (Aβ) and insulin are amyloidogenic peptides, and they play a critical role in Alzheimer's disease (AD) and type-2 diabetes (T2D). Misfolded or aggregated Aβ and glycated insulin are commonly found in AD and T2D patients, respectively, and exhibit neurotoxicity and oxidative stress. The present study examined the anti-Aβ

Topics: Amyloid beta-Peptides; Benzofurans; Dioxins; Glycation End Products, Advanced; Lipid Peroxidation; Molecular Docking Simulation; Molecular Structure; Phaeophyceae; Phloroglucinol; Protein Aggregation, Pathological

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases with a multifactorial nature. β-Secretase (BACE1) and acetylcholinesterase (AChE), which are required for the production of neurotoxic β-amyloid (Aβ) and the promotion of Aβ fibril formation, respectively, are considered as prime therapeutic targets for AD. In our efforts towards the development of potent multi-target, directed agents for AD treatment, major phlorotannins such as eckol, dieckol, and 8,8'-bieckol from

Topics: ADAM17 Protein; Alzheimer Disease; Amyloid Precursor Protein Secretases; Aspartic Acid Endopeptidases; Benzofurans; Cholinesterase Inhibitors; Cholinesterases; Dioxins; Molecular Docking Simulation; Seaweed; Tannins

Alzheimer disease (AD) is a neurodegenerative disorder characterized by excessive accumulation of amyloid-beta peptide (Aβ) and progressive loss of neurons. Therefore, the inhibition of Aβ-induced neurotoxicity is a potential therapeutic approach for the treatment of AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Apoptosis; Benzofurans; Cyclooxygenase 2; Dioxins; Down-Regulation; Drug Evaluation, Preclinical; MAP Kinase Signaling System; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase Type II; PC12 Cells; Peptide Fragments; Phaeophyceae; Rats; Seaweed

Eckol and dieckol are important phlorotannins found in edible brown algae including Eisenia bicyclis, Ecklonia stolonifera, and others. Inhibition of monoamine oxidase (MAO) play an important role in the early management of Parkinson's disease (PD). The aim of this study was to determine the effectiveness of eckol and dieckol isolated from the methanolic extract of E. bicyclis against PD by the inhibition of human MAO-A and MAO-B (hMAO-A and hMAO-B). A sensitive enzyme-based chemiluminescent assay and kinetics methods were used to investigate enzyme inhibition and mode of inhibition. A molecular docking simulation was performed to clarify the binding characteristics of eckol and dieckol to hMAO-A and hMAO-B. The results suggested that methanolic extract of E. bicyclis and its isolated phlorotannins, eckol and dieckol, have potent inhibitory activity against hMAO-A and hMAO-B. The enzyme-based kinetics results demonstrated eckol mixed and non-competitive inhibition of hMAO-A and hMAO-B, respectively, while dieckol non-competitively inhibited both hMAOs. Molecular docking simulation predicted that eckol and dieckol exhibit higher binding affinity towards hMAO-A and hMAO-B through hydrogen bonding and hydrophobic interactions. These findings implicate eckol and dieckol as inhibitors of hMAOs that might be of potential value in the management of PD.

Topics: Benzofurans; Dioxins; Dose-Response Relationship, Drug; Humans; Molecular Docking Simulation; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Phaeophyceae; Structure-Activity Relationship

As part of our efforts to isolate anti-hepatotoxic agents from marine natural products, we screened the ability of 14 edible varieties of Korean seaweed to protect against doxorubicin-induced hepatotoxicity in primary rat hepatocytes.. Among the crude extracts of two Chlorophyta (Codium fragile and Capsosiphon fulvescens), seven Phaeophyta (Undaria pinnatifida, Sargassum thunbergii, Pelvetia siliquosa, Ishige okamurae, Ecklonia cava, Ecklonia stolonifera and Eisenia bicyclis), five Rhodophyta (Chondrus ocellatus, Gelidium amansii, Gracilaria verrucosa, Symphycladia latiuscula and Porphyra tenera), and the extracts of Ecklonia stolonifera, Ecklonia cava, Eisenia bicyclis and Pelvetia siliquosa exhibited significant protective effects on doxorubicin-induced hepatotoxicity, with half maximal effective concentration (EC50) values of 2.0, 2.5, 3.0 and 15.0 μg/ml, respectively.. Since Ecklonia stolonifera exhibits a significant protective potential and is frequently used as foodstuff, we isolated six phlorotannins, including phloroglucinol (1), dioxinodehydroeckol (2), eckol (3), phlorofucofuroeckol A (4), dieckol (5) and triphloroethol-A (6). Phlorotannins 2 ∼ 6 exhibited potential protective effects on doxorubicin-induced hepatotoxicity, with corresponding EC50 values of 3.4, 8.3, 4.4, 5.5 and 11.5 μg/ml, respectively.. The results clearly demonstrated that the anti-hepatotoxic effects of Ecklonia stolonifera and its isolated phlorotannins are useful for further exploration and development of therapeutic modalities for treatment of hepatotoxicity.

Topics: Animals; Benzofurans; Dioxins; Doxorubicin; Hepatocytes; Male; Phaeophyceae; Phloroglucinol; Protective Agents; Rats; Rats, Sprague-Dawley; Seaweed

In this study the protective effect of phlorotannins, including phloroglucinol, eckol, dieckol, eckstolonol and triphloroethol A, isolated from brown algae Ecklonia cava was investigated against AAPH-induced oxidative stress toxicity in zebrafish embryos. Zebrafish embryos were exposed to AAPH and compared with other groups that were co-exposed with phlorotannins until 2-days post-fertilisation. All phlorotannins scavenged intracellular ROS and prevented lipid peroxidation and reduced AAPH-induced cell death in zebrafish embryos. Negative changes in morphological phenomena, such as pericardial oedema, yolk sac oedema, and growth retardation in zebrafish embryos exposed to AAPH were not observed in groups exposed to phlorotannins. These results clearly indicate that phlorotannins possess prominent antioxidant activity against AAPH-mediated toxicity and might be potential therapeutic agents for treating or preventing several diseases implicated with oxidative stress. This study provides a useful tool for examining the protective effect of antioxidants against AAPH-induced oxidative stress in an alternative in vivo model.

Topics: Amidines; Animals; Antioxidants; Benzofurans; Dioxins; Oxidative Stress; Phaeophyceae; Phloroglucinol; Protective Agents; Zebrafish

Pancreatic lipase is a potential therapeutic target for the treatment of diet-induced obesity in humans. In an ongoing search for new pancreatic lipase inhibitors from natural sources, a methanolic extract of marine brown algae, Eisenia bicyclis, showed a significant inhibitory effect against pancreatic lipase. Bioassay-guided isolation of this methanolic extract using a pancreatic lipase inhibitory assay led to the isolation and identification of six known phlorotannins: eckol (1), fucofuroeckol A (2), 7-phloroeckol (3), dioxindehydroeckol (4), phlorofucofuroeckol A (5), and dieckol (6). The structures were established on the basis of nuclear magnetic resonance and mass spectrometry spectroscopic data interpretation. Among the isolated phloroglucinol polymers, compounds 2 and 3 showed potent inhibitory effects on pancreatic lipase with IC₅₀ values ranging from 37.2 ± 2.3 to 12.7 ± 1.0 μM, respectively.

Topics: Animals; Benzofurans; Dioxins; Inhibitory Concentration 50; Lipase; Oxindoles; Phaeophyceae; Swine; Tannins

In this Letter, we first investigated the barrier protective effects of eckol and its derivatives against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. Data showed that eckol (1) and dieckol (2) inhibited lipopolysaccharide (LPS)-mediated barrier disruption and transendothelial migration of leukocytes to human endothelial cells. Eckol (1) also suppressed acetic acid induced-hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Interestingly, the barrier protective effects of dieckol (2) were better than those of eckol (1) and hydroxyl groups in dieckol (2) positively regulate protective effects.

Topics: Acetic Acid; Animals; Carboxymethylcellulose Sodium; Cell Membrane Permeability; Cell Movement; Dioxins; Human Umbilical Vein Endothelial Cells; Humans; Leukocytes; Lipopolysaccharides; Mice; Protective Agents

The phlorotannins (phloroglucinol, eckol, and dieckol) are active compounds found in Eisenia bicyclis, and have been widely investigated for their antioxidant, anti-tumor, and anti-cancer activities. In this study, we investigated the protective effects of these phlorotannins against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice treated by high mobility group box 1 protein (HMGB1), and the signaling pathways involved. The protective activities of the phlorotannins were determined by measuring permeability, leukocyte adhesion and migration, and the activations of pro-inflammatory proteins in HMGB1-activated HUVECs. We found that the phlorotannins inhibited; lipopolysaccharide (LPS)-induced HMGB1 release, HMGB1-mediated barrier disruption, the expressions of cell adhesion molecules (CAMs), and the adhesion/transendothelial migration of leukocytes to human endothelial cells. The phlorotannins also suppressed acetic acid induced-hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that the hydroxyl groups on dieckol positively regulated these vascular barrier protective effects. Collectively, these results suggest that phloroglucinol, eckol, and dieckol protect vascular barrier integrity by inhibiting hyperpermeability, the expressions of CAMs, and the adhesion and migration of leukocytes, which confirms their potential usefulnesses for the treatment of vascular inflammatory diseases.

Topics: Animals; Benzofurans; Blood Vessels; Blotting, Western; Cell Adhesion Molecules; Cell Membrane Permeability; Cell Movement; Cell Survival; Dioxins; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Female; HMGB1 Protein; Humans; Inflammation; Kelp; Lipopolysaccharides; Mice; Mice, Inbred ICR; Phloroglucinol; Spectrometry, Mass, Electrospray Ionization; Tannins; Toll-Like Receptor 4

In order to develop new anticoagulant agents, two single compounds (eckol and dieckol) were isolated from Eisenia bicyclis and examined their anticoagulant activities by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT) as well as cell-based thrombin and activated factor X (FXa) generation activities. And the effects of eckol and dieckol on the expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). Data showed that eckol and dieckol prolonged aPTT and PT significantly and inhibited thrombin and FXa activities. They also inhibited the generation of thrombin or FXa in HUVECs. In accordance with these anticoagulant activities, eckol or dieckol showed anticoagulant effect in vivo. Furthermore, eckol and dieckol inhibited TNF-α induced PAI-1 production and the ratio between PAI-1 and t-PA was found to be significantly decreased by eckol and dieckol. Surprisingly, these anticoagulant and profibrinolytic effects of dieckol were better than those of eckol indicating that hydroxyl group in eckol positively regulated anticoagulant function of eckol. Therefore, these results suggest that eckol or dieckol possesses antithrombotic activities and provides a possibility to develop as an agent for the anticoagulation.

Topics: Animals; Benzofurans; Dioxins; Enzyme-Linked Immunosorbent Assay; Factor Xa; Fibrinolysis; Fibrinolytic Agents; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice; Mice, Inbred ICR; Prothrombin; Thrombin; Tissue Plasminogen Activator; Tumor Necrosis Factor-alpha

The present work investigates protein tyrosine phosphatase 1B (PTP1B) and the α-glucosidase inhibitory activities of two edible brown algae, Ecklonia stolonifera and Eisenia bicyclis, as well as in their isolated phlorotannins. Since the individual extracts and fractions showed significant inhibitory activities, column chromatography was performed to isolate six phlorotannins, phloroglucinol (1), dioxinodehydroeckol (2), eckol (3), phlorofurofucoeckol-A (4), dieckol (5), and 7-phloroeckol (6). Phlorotannins 3-6 were potent and noncompetitive PTP1B inhibitors with IC(50) values ranging from 0.56 to 2.64 µM; 4-6 exhibited the most potent α-glucosidase inhibition with IC(50) values ranging from 1.37 to 6.13 µM. Interestingly, 4 and 6 were noncompetitive, while 5 exhibited competitive inhibition in an α-glucosidase assay. E. stolonifera and E. bicyclis as well as their isolated phlorotannins therefore possessed marked PTP1B and α-glucosidase inhibitory activities; this could lead to opportunities in the development of therapeutic agents to control the postprandial blood glucose level and thereby prevent diabetic complications.

Topics: alpha-Glucosidases; Benzofurans; Blood Glucose; Complex Mixtures; Diabetes Mellitus; Dioxins; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypoglycemic Agents; Kinetics; Magnetic Resonance Spectroscopy; Phaeophyceae; Phloroglucinol; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Solutions; Spectrophotometry; Tannins; Yeasts

Ecklonia stolonifera is a rich source of phlorotannins, which are responsible for the potent pharmacological effects associated with this seaweed. The purpose of this study was to develop a reversed-phase high-performance liquid chromatography method for the simultaneous determination of three major phlorotannins, eckol, dieckol, and phlorofucofuroeckol-A, in the extracts of Ecklonia stolonifera. The optimal chromatographic conditions were achieved on a Thermo Hypersil Gold C-18 column (250 x 4.6 mm i.d., 5 microm) using linear gradient elution of acetonitrile and water containing 0.1% formic acid at UV 254 nm. The separated phlorotannins were identified by liquid chromatography-mass spectrometry. The high-performance liquid chromatography method showed good linearity (r2 > 0.998), precision (1.4-9.5%), and accuracy (93.9-108.7%). The limits of detection ranged from 0.06 to 0.30 microg/mL and the lower limits of quantitation ranged from 0.2 to 1.0 microg/mL. Among phlorotannins, dieckol was the most abundant in both ethanol and ethyl acetate extracts of Ecklonia stolonifera.

Topics: Benzofurans; Chromatography, High Pressure Liquid; Dioxins; Phaeophyceae; Plants, Medicinal; Spectrometry, Mass, Electrospray Ionization; Tannins

We conducted this study to isolate novel anti-hyperlipidemic agents derived from natural marine products. To accomplish this, we investigated the effects of ethanolic (EtOH) extracts of Ecklonia stolonifera and its phlorotannin constituents, eckol and dieckol, on serum lipid levels in rats with hyperlipidemia that was induced by a high-cholesterol diet or poloxamer 407. Treatment with the EtOH extracts of E. stolonifera and its phlorotannin-rich ethyl acetate (EtOAc) and n-butanol (n-BuOH) fractions induced a significant reduction in triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) levels, as well as a significant increase in the high-density lipoprotein-cholesterol (HDLC) level in hyperlipidemic rats. However, treatment with the water (H(2)O) fraction did not exert any significant effects on the serum levels of hyperlipidemic rats. In addition, eckol and dieckol isolated from the active EtOAc fraction induced a significant reduction in serum TG, TC, and LDL-C levels, as well as in the atherogenic index (A.I.). Furthermore, treatment with dieckol induced a greater decrease in the serum TG, TC, and LDL-C levels of hyperlipidemic rats than eckol or lovastatin, as well as an increase in the serum HDL-C levels. Taken together, these results suggest that phlorotannins such as eckol and dieckol have the potential for use for the prevention of hyperlipidemic atherosclerosis.

Topics: Animals; Benzofurans; Cholesterol, Dietary; Diet; Dioxins; Ethanol; Freeze Drying; Hyperlipidemias; Hypolipidemic Agents; Male; Phaeophyceae; Poloxamer; Rats; Rats, Sprague-Dawley; Solvents; Tannins; Triglycerides

In order to develop new anti-photoaging agents, we examined the inhibitory effects of 29 seaweed extracts on transcriptional activities of NF-kappaB and AP-1, and MMP-1 expression. The extracts from 3 species of Alariaceae, Eisenia bicyclis, Ecklonia cava and Ecklonia stolonifera, have showed strong inhibition of both NF-kappaB and AP-1 reporter activity, which were well correlated with their abilities to inhibit MMP-1 expression. In addition, MMP-1 expression was dramatically attenuated by treatment with eckol or dieckol which were purely isolated from E. stolonifera, indicating that these compounds are active principles to inhibit MMP-1 expression in human dermal fibroblasts. Taken together, our data demonstrate the inhibitory effect of eckol and dieckol from Ecklonia species on MMP-1 expression in human dermal fibroblasts and provide a possibility to develop as an agent for the prevention and treatment of skin aging.

Topics: Base Sequence; Benzofurans; Blotting, Western; Cells, Cultured; Dioxins; DNA Primers; Fibroblasts; Humans; Matrix Metalloproteinase 1; Phaeophyceae; Reverse Transcriptase Polymerase Chain Reaction; Skin

Chronic exposure of the skin to ultraviolet B (UVB) radiation induces oxidative stress, which plays a crucial role in the induction of skin cancer. In this study, the effect of dietary feeding and topical application of brown algae polyphenols on UVB radiation-induced skin carcinogenesis in SKH-1 mice was investigated. SKH-1 hairless mice were randomly divided into 9 groups, including control, UVB control and treatment groups. They were treated orally (0.1% and 0.5% with AIN-76 diet, w/w) and topically (3 and 6 mg/0.2 ml of vehicle) with brown algae polyphenols and irradiated with UVB for 26 weeks. Dietary feeding (0.1% and 0.5%) of brown algae polyphenols significantly reduced tumor multiplicity (45% and 56%) and tumor volume (54% and 65%), and topical administration (3 and 6 mg) significantly decreased tumor multiplicity (60% and 46%) and tumor volume (66% and 57%), respectively, per tumor-bearing mouse. Dietary feeding and topical administration of the polyphenols also inhibited tumor incidence by 6% and 21%, respectively, but the results were not significant. Dietary and topical administration of the polyphenols markedly inhibited cyclooxygenase-2 activity and cell proliferation. These observations show that brown algae polyphenols have an antiphotocarcinogenic effect which may be associated with the prevention of UVB-induced oxidative stress, inflammation, and cell proliferation in the skin.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Benzofurans; Blotting, Western; Cell Proliferation; Cyclooxygenase 2; Dinoprostone; Dioxins; Epidermis; Female; Flavonoids; Gene Expression; Immunohistochemistry; Mice; Molecular Structure; Neoplasms, Radiation-Induced; Phaeophyceae; Phenols; Polyphenols; Proliferating Cell Nuclear Antigen; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; Skin; Skin Neoplasms; Ultraviolet Rays