tannins and eckol

Brown seaweed (Phaeophyceae) polyphenolics such as phlorotannins are ascribed various biological activities, including neuroprotection. Of these seaweeds, Ecklonia radiata (E. radiata) is found abundantly along South Australian coastal regions; however it has not been explored for various biological activities relative to any component phlorotannins previously ascribed neuroprotective capacity. In the present study, we evaluated neuroprotective activity against the neurotoxic amyloid β protein (Aβ1-42) of an ethanol extract of E. radiata compared with various additional solvent-solubilised fractions in a neuronal PC-12 cell line. The ethyl acetate fraction comprising 62% phlorotannins demonstrated the most efficacious neuroprotective activity, inhibiting neurotoxicity at all Aβ1-42 concentrations. In addition, this fraction demonstrated a significant reduction in Aβ aggregate density, but did not alter overall aggregate morphology. Centrifugal partitioning chromatography was used to isolate the major component, eckol, in high yield and liquid chromatography-mass spectrometry was used to characterize the major components of the ethyl acetate fraction. Our results demonstrate that the prevalence of eckol-type phlorotannins are associated with neuroprotective bioactivity of E. radiata, suggestive of potential nutraceutical and biopharmaceutical uses of this brown seaweed phlorotannin in dementia.

Topics: Amyloid beta-Peptides; Animals; Australia; Biological Products; Cell Survival; Dioxins; Humans; Neurons; Neuroprotective Agents; Neurotoxicity Syndromes; PC12 Cells; Peptide Fragments; Phaeophyceae; Plant Extracts; Rats; Seaweed; Tannins

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

Interest in phlorotannins has increased in recent years largely due to antioxidant capacity, however, the redox mechanism of phlorotannins is still obscure. In the present study, the electrochemical oxidation mechanisms of eckol (EL) and phlorofucofuroeckol-A (PFF-A), two representative phlorotannin compounds, were comparatively analyzed in a wide pH range using cyclic and differential pulse voltammetry as well as spectroscopic assay. The voltammetric study revealed that EL and PFF-A were successively oxidized in three pH-dependent steps. Moreover, it was found that the PFF-A presented a stronger proton and electron transferring activity as compared to EL since PFF-A exhibited lower acid-base dissociation constant (pK

Topics: Antioxidants; Benzofurans; Cell Culture Techniques; Dioxins; Humans; Oxidation-Reduction; Phaeophyceae; Reactive Oxygen Species; Spectrum Analysis; Superoxides; Tannins

The dramatic increase in obesity-related diseases emphasizes the need to elucidate the cellular and molecular mechanisms underlying fat metabolism. Inhibition of adipocyte differentiation has been suggested to be an important strategy for preventing or treating obesity. In our previous study, we characterized an Ecklonia stolonifera extract and non-polar fractions thereof, including dichloromethane and ethyl acetate fractions. We showed that these fractions inhibited adipocyte differentiation and lipid formation/accumulation in 3T3-L1 preadipocytes, as assessed by Oil Red O staining. As part of our ongoing search for anti-obesity agents derived from E. stolonifera, in this work, we characterized five known phlorotannins, including phloroglucinol, eckol, dieckol, dioxinodehydroeckol, and phlorofucofuroeckol A, all of which were isolated from the active ethyl acetate fraction of E. stolonifera. We determined the chemical structures of these phlorotannins through comparisons of published nuclear magnetic resonance (NMR) spectral data. Furthermore, we screened these phlorotannins for their abilities to inhibit adipogenesis over a range of concentrations (12.5-100 μM). Of these five phlorotannins, phloroglucinol, eckol, and phlorofucofuroeckol A significantly concentration-dependently inhibited lipid accumulation in 3T3-L1 cells without affecting cell viability. In addition, the five isolated phlorotannins also significantly reduced the expression levels of several adipocyte marker genes, including proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), although they did so to different extents. These results suggest that the molecular weight of a phlorotannin is an important factor affecting its ability to inhibit adipocyte differentiation and modulate the expression levels of adipocyte marker genes.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Protein-alpha; CCAAT-Enhancer-Binding Proteins; Dioxins; Down-Regulation; Mice; Obesity; Phaeophyceae; Phytotherapy; Plant Extracts; PPAR gamma; Tannins

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

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

Four kinds of phlorotannins having antioxidant activity were isolated from the ethyl acetate fraction of Ecklonia stolonifera ethanolic extract. The structures of the phlorotannins were determined on the basis of spectroscopic evidence, including 1D and 2D nuclear magnetic resonance. The isolated phlorotannins showed potential radical-scavenging activities against 2,2-diphenyl-1-picrylhydrazyl and suppressed the intracellular reactive oxygen species in tacrine-treated HepG2 cells. Among them, eckol and 2-phloroeckol showed hepatoprotective activity in tacrine-treated HepG2 cells; however, phlorofucofuroeckol B and 6,6'-bieckol did not show the activity, even though having high antioxidant activity. Both eckol and 2-phloroeckol inhibited the expression of Fas-mediated cell-death proteins, including tBid, caspase-3, and poly(ADP-ribose) polymerase, and suppressed the release of cytochrome c from mitochondria to cytosol in a dose-dependent manner in tacrine-treated HepG2 cells. These results suggest that eckol and 2-phloroeckol are the principal hepatoprotective constituents of the ethyl acetate fraction of E. stolonifera ethanolic extract.

Topics: Antioxidants; Dioxins; Hep G2 Cells; Humans; Mitochondria; Phaeophyceae; Protective Agents; Reactive Oxygen Species; Tacrine; Tannins

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