• Journal of Microbiology and Biotechnology
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• v.29 no.1
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• pp.11-20
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• 2019

Ecklonia cava, an edible marine brown alga (Laminariaceae), is a rich source of bioactive compounds such as fucoidan and phlorotannins. Ecklonia cava extract (ECE) was prepared using 70% ethanol extraction and ECE contained 67% and 10.6% of total phlorotannins and dieckol, respectively. ECE treatment significantly inhibited receptor activator of nuclear $factor-{\kappa}B$ ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells and pit formation in bone resorption assay (p <0.05). Moreover, it suppressed RANKL-induced $NF-{\kappa}B$ and mitogen-activated protein kinase signaling in a dose dependent manner. Downregulated osteoclast-specific gene (tartrate-resistant acid phosphatase, cathepsin K, and matrix metalloproteinase-9) expression and osteoclast proliferative transcriptional factors (nuclear factor of activated T cells-1 and c-fos) confirmed ECE-mediated suppression of osteoclastogenesis. ECE treatment ($100{\mu}g/ml$) increased heme oxygenase-1 expression by 2.5-fold and decreased intercellular reactive oxygen species production during osteoclastogenesis. The effective inhibition of RANKL-stimulated osteoclast differentiation and oxidative stress by ECE suggest that ECE has therapeutic potential in alleviating osteoclast-associated disorders.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.219-228
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• 2015

Excessive microglial activation and subsequent neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK), Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial conditioned media system. Our results demonstrated that treatment of anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide (LPS, $1{\mu}g/ml$)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of $gp91^{phox}$, which is the catalytic component of NADPH oxidase complex responsible for microglial reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial conditioned media containing neurotoxic secretary molecules. These neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using enhanced green fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and NADPH oxidase-mediated pathways.

• ALGAE
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• v.30 no.3
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• pp.241-246
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• 2015

This research was conducted to develop effective and safe marine-derived antiviral compounds against norovirus. The ethyl acetate (EtOAc)-extract from Eisenia bicyclis exhibited strong antiviral activity against murine norovirus (MNV) as a norovirus surrogate. Among the phlorotannins from E. bicyclis, dieckol (DE) and phlorofucofuroeckol-A (PFF) were known to possess the strongest antibacterial activity. In this study, DE and PFF were evaluated for antiviral activity against MNV. DE and PFF exhibited strong anti-MNV activity with 50% effective concentration ($EC_{50}$) of $0.9{\mu}M$. However, PFF exhibited more effective antiviral activity against MNV with higher selective index (668.87) than that of DE (550.60), due to its lower cell toxicity against RAW 264.7. This is the first report on the anti-MNV activity of phlorotannins from seaweed. The results obtained in this study suggest that the phlorotannins could be used as a potential source of natural antiviral agents.

• Fisheries and Aquatic Sciences
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• v.16 no.1
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• pp.1-5
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• 2013

To assess the feasibility of phlorotannins from Eisenia bicyclis as cancer chemopreventative agents, we tested whether they induced quinone reductase (QR) in Hepa1c1c7 cells. The ethyl acetate (EtOAc) soluble fraction obtained from E. bicyclis exhibited a QR induction activity in Hepa1c1c7 cells. Successive column chromatography of the active EtOAc fraction resulted in the isolation of four phlorotannins. Their structures were elucidated using one- and two-dimensional nuclear magnetic resonance spectroscopic techniques and characterized as phloroglucinol (1), dioxinodehydroeckol (2), dieckol (3), and fucofuroeckol-A (4). Among these compounds, fucofuroeckol-A (4) showed moderate QR induction activity, and dioxinodehydroeckol (2) exhibited potent QR induction potency with $2.05{\pm}0.04$ fold induction at a concentration of $50{\mu}M$ compared to the dimethyl sulfoxide solvent-treated control cells. However, phloroglucinol (1) and dieckol (3) exerted no detectable QR induction activity in Hepa1c1c7 cells. These results suggest that dioxinodehydroeckol could serve as a useful cancer chemopreventive chemical.

• Journal of Microbiology and Biotechnology
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• v.24 no.4
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• pp.465-474
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• 2014

This study was performed to investigate the inhibitory effects of brown algae extracts on histamine production in mackerel muscle. First, antimicrobial activities of brown algae extracts against Morganella morganii were investigated using a disk diffusion method. An ethanol extract of Ecklonia cava (ECEE) exhibited strong antimicrobial activity. The minimum inhibitory concentration (MIC) of ECEE was 2 mg/ml. Furthermore, the brown algae extracts were examined for their ability to inhibit crude histidine decarboxylase (HDC) of M. morganii. The ethanol extract of Eisenia bicyclis (EBEE) and ECEE exhibited significant inhibitory activities (19.82% and 33.79%, respectively) at a concentration of 1 mg/ml. To obtain the phlorotannin dieckol, ECEE and EBEE were subjected to liquid-liquid extraction, silica gel column chromatography, and HPLC. Dieckol exhibited substantial inhibitory activity with an $IC_{50}$ value of 0.61 mg/ml, and exhibited competitive inhibition. These extracts were also tested on mackerel muscle. The viable cell counts and histamine production in mackerel muscle inoculated with M. morganii treated with ${\geq}2.5 $ MIC of ECEE (weight basis) were highly inhibited compared with the untreated sample. Furthermore, treatment of crude HD-Cinoculated mackerel muscle with 0.5% ECEE and 0.5% EBEE (weight basis), which exhibited excellent inhibitory activities against crude HDC, reduced the overall histamine production by 46.29% and 56.89%, respectively, compared with the untreated sample. Thus, these inhibitory effects of ECEE and EBEE should be helpful in enhancing the safety of mackerel by suppressing histamine production in this fish species.

• Korean Journal of Pharmacognosy
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• v.37 no.2 s.145
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• pp.92-96
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• 2006

Six phlorotannins were isolated from Ecklonia cava, a brown alga belonging to Alariaceae, collected offshore Jeju Island. Among the phlorotannins, dieckol showed strong elastase inhibition and hyaluronidase ingibition.

• Food Science and Industry
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• v.51 no.4
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• pp.334-342
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• 2018

People in Korea, a peninsular, have acquired a variety of marine food resources including seaweeds. Ecklonia stolonifera, a brown algae, is commonly dwelling in Korean coasts and their cultivation methods were developed for a mass-production. Recently, studies have revealed that Ecklonia stolonifera is a promising material for the development of health functional foods. In an effort to carefully review the current understating in the effects and mechanisms of Ecklonia stolonifera on liver functions by deduction from relevant literatures, the effective components were identified as phlorotannins, including dieckol, eckstolonol, eckol, phlorofucofuroeckol A, and phlorosterol. Their aiding action on the hepatic functions is categorized as follows. A) Regulation of oxidative stress by anti-oxidant capacity, B) Protection of hepatocytes from toxins, C) Prevention of alcoholic fatty liver and fibrogenesis, D) Regulation of chronic disease by improvement of inflammatory responses and lipid metabolisms, and E) indirect benefit conferred by a personal total wellness.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.190.2-190.2
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• 2003

In the course of search for various bioactive compounds from marine algae, we found strong antioxidant activity of the methanolic extract of the brown alga G. elliptica. Chromatographic purification [ODS flash, gel-filtration on Sephadex LH-20, HPLC] of the BuOH layer of the methanolic extract afforded two known polyphenolic compounds, 6,6'-bieckol (1) and dieckol (2). Compound 1 showed acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities, free radical scavenging activity on DPPH (1,1-diphenyl-2-picryl-hydazyl) with IC$\_$50/ values of 91.2, 45.6 and 15.5 $\mu\textrm{g}$/$m\ell$, respectively. (omitted)

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.194-198
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• 2004

Reactive oxygen species (ROS) play an important role in the pathogenesis of many human degenerative diseases such as cancer, aging, arteriosclerosis, and rheumatism. Much attention has been focused on the development of safe and effective antioxidants. To discover sources of antioxidative activity in marine algae, extracts from 17 kinds of seaweed were screened for their inhibitory effect on total ROS generation in kidney homogenate using 2',7'-dichlorofluorescein diacetate (DCFH-DA). ROS inhibition was seen in three species: UIva pertusa, Symphyocladia latiuscula, and Ecklonia stolonifera. At a final concentration of 25 $\mu\textrm{g}$/mL, U. pertusa inhibited 85.65$\pm$20.28％ of total ROS generation, S. latiscula caused 50.63$\pm$0.09％ inhibitory, and the Ecklonia species was 44.30$\pm$7.33％ inhibition. E. stolonifera OKAMURA (Lam-inariaceae), which belongs to the brown algae, has been further investigated because it is commonly used as a foodstuff in Korea. Five compounds, phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5), isolated from the ethyl acetate soluble fraction of the methanolic extrclct of E. stolonifera inhibited total ROS generation.

• Archives of Pharmacal Research
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• v.28 no.12
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• pp.1376-1380
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• 2005

In this study, ethanolic extracts from 18 seaweed variants were assessed for hepatoprotective activity against tacrine-induced cytotoxicity in Hep G2 cells. Only one of these, Ecklonia stolonifera Okamura (Laminariaceae), a member of the brown algae, exhibited promising hepatoprotective activity. Bioassay-guided fractionation of the active ethyl acetate (EtOAc) soluble fraction obtained from the ethanolic extract of E. stolonifera, resulted in the isolation of several phlorotannins [phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5)]. Compounds 2 and 4 were determined to protect Hep G2 cells against the cytotoxic effects of tacrine, with $EC_{50}$ values of 62.0 and 79.2 $\mu$g/mL, respectively. Silybin, a well characterized hepatoprotective agent, was used as a positive control, and exhibited an $EC_{50}$ value of 50.0 $\mu$g/mL. It has been suggested that the phlorotannins derived from marine brown algae might prove useful sources in the development of novel hepatoprotective agents.