PMID: 

Pharm Biol. 2017 Dec ;55(1):1149-1154. PMID: 28219252

Abstract Title: 

A phlorotannin constituent of Ecklonia cava alleviates postprandial hyperglycemia in diabetic mice.

Abstract: 

CONTEXT: 2,7″-Phloroglucinol-6,6'-bieckol is a type of phlorotannin isolated from brown algae, Ecklonia cava Kjellman (Phaeophyceae; Laminareaceae). 2,7″-Phloroglucinol-6,6'-bieckol mediates antioxidant activities. However, there has been no research on improving postprandial hyperglycaemia using 2,7″-phloroglucinol-6,6'-bieckol.OBJECTIVE: This study investigated the inhibitory effects of 2,7″-phloroglucinol-6,6'-bieckol on activities of α-glucosidase and α-amylase as well as its alleviating effect on postprandial hyperglycaemia in streptozotocin-induced diabetic mice.MATERIALS AND METHODS: α-Glucosidase and α-amylase inhibitory assays were carried out. The effect of 2,7″-phloroglucinol-6,6'-bieckol on hyperglycaemia after a meal was measured by postprandial blood glucose in streptozotocin-induced diabetic and normal mice. The mice were treated orally with soluble starch (2 g/kgBW) alone (control) or with 2,7″-phloroglucinol-6,6'-bieckol (10 mg/kg bw) or acarbose (10 mg/kg BW) dissolved in 0.2 mL water. Blood samples were taken from tail veins at 0, 30, 60, and 120 min and blood glucose was measured by a glucometer.RESULTS: 2,7″-Phloroglucinol-6,6'-bieckol showed higher inhibitory activities than acarbose, a positive control against α-glucosidase and α-amylase. The ICvalues of 2,7″-phloroglucinol-6,6'-bieckol against α-glucosidase and α-amylase were 23.35 and 6.94 μM, respectively, which was found more effective than observed with acarbose (α-glucosidase ICof 130.04 μM; α-amylase ICof 165.12 μM). In normal mice, 2,7″-phloroglucinol-6,6'-bieckol significantly suppressed the postprandial hyperglycaemia caused by starch. The 2,7″-phloroglucinol-6,6'-bieckol administration group (2349.3 mmol·min/L) had a lower area under the curve (AUC) glucose response than the control group (2690.83 mmol·min/L) in diabetic mice.DISCUSSION AND CONCLUSION: 2,7″-Phloroglucinol-6,6'-bieckol might be used as an inhibitor of α-glucosidase and α-amylase as well as to delay absorption of dietary carbohydrates.

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PMID: 

J Agric Food Chem. 2017 May 17 ;65(19):3811-3818. Epub 2017 May 5. PMID: 28459555

Abstract Title: 

Ameliorative Effect of Ecklonia cava Polyphenol Extract on Renal Inflammation Associated with Aberrant Energy Metabolism and Oxidative Stress in High Fat Diet-Induced Obese Mice.

Abstract: 

Immoderate fat accumulation causes both oxidative stress and inflammation, which can induce kidney damage in obesity. Previously, Ecklonia cava has shown anti-inflammatory and antioxidative effects. Our group aimed to investigate whether E. cava polyphenol extract (ECPE) improves renal damage in high fat diet (HFD)-induced obese mice through regulation of not only energy metabolism but also oxidative stress and inflammation. After obesity induction by HFD, the mice were treated with different dosages of ECPE (100 or 500 mg/kg/day) by gavage for 12 weeks. ECPE treatment lowered the protein levels related to lipid accumulation (SREBP1c, ACC&FAS), inflammation (NLRP3 inflammasome, NFκB, MCP-1, TNF-α&CRP), and oxidative stress (Nrf2, HO-1, MnSOD, NQO1, GPx, 4-HNE and protein carbonyls) in HFD induced obese mice. Moreover, ECPE supplementation significantly up-regulated renal SIRT1, PGC-1α, and AMPK, which are associated with renal energy metabolism. Consequently, the results provide novel insights into the anti-inflammatory roles of ECPE in obesity-induced renal inflammation.

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PMID: 

Molecules. 2017 May 10 ;22(5). Epub 2017 May 10. PMID: 28489052

Abstract Title: 

Crude Ecklonia cava Flake Extracts Attenuate Inflammation through the Regulation of TLR4 Signaling Pathway in LPS-Induced RAW264.7 Cells.

Abstract: 

We investigated the beneficial effects of the crudeflake (CEF), which is a residual product after polyphenol extraction from, on inflammation in LPS-stimulated RAW264.7 cells. A group of five different CEF extracts was obtained by a preparation process using water, hydrochloric acid or temperature. We observed that large-size (>19 kDa) CEF extract, which was extracted with water at 95°C (CEF-W, 95 °C), suppressed the production of inflammatory cytokines by inhibiting its mRNA expression in LPS-induced RAW264.7 cells. TLR4 signaling involvements were negatively regulated by CEF-W, 95 °C. CEF-W, 95 °C repressed the translocation of NF-κB from cytoplasm into nucleus in LPS-induced RAW264.7 cells. CEF-W, 95 °C attenuated the phosphorylation of TBK1 and IRF3 by inhibiting the phosphorylation of ERK. Taken together, we demonstrated that large-size CEF-W, 95 °C may act as a negative regulator of inflammation through the suppression of TLR4 signaling constituents in LPS-induced RAW264.7 cells.

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PMID: 

J Med Food. 2017 Oct ;20(10):944-950. Epub 2017 Aug 17. PMID: 28816580

Abstract Title: 

Cardioprotective Effects of a Phlorotannin Extract Against Doxorubicin-Induced Cardiotoxicity in a Rat Model.

Abstract: 

Long-term therapy with doxorubicin (DOX) is associated with high incidence of cumulative and irreversible dilated cardiomyopathy. The goal of this study was to evaluate the cardioprotective effects and safety of a phlorotannin extract from a brown algae Ecklonia cava (Seapolynol™, SPN) against DOX-induced cardiotoxicity in a rat model. A total of 42 rats were divided into six groups: control, low-dose SPN (LDS), high-dose SPN (HDS), DOX, DOX with low-dose SPN (DOX+LDS), and DOX with high-dose SPN (DOX+HDS). Echocardiography was performed at baseline and after 6 weeks. Inleft ventricular (LV) ejection fraction, DOX and DOX+LDS groups showed significant decreases (P 

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PMID: 

Food Chem. 2018 Aug 15 ;257:128-134. Epub 2018 Mar 6. PMID: 29622188

Abstract Title: 

Inhibitory activity of minor phlorotannins from Ecklonia cava onα-glucosidase.

Abstract: 

α-Glucosidase is an enzyme that plays a key role in raising blood sugar level and is considered a good target for developing drugs to treat type 2 diabetes. This study was performed to evaluate the inhibition of the catalytic reaction of α-glucosidase by minor phlorotannin derivatives (1-5) from Ecklonia cava. These derivatives demonstrated inhibitory activity, with ICvalues ranging from 2.3 ± 0.1 to 59.8 ± 0.8 μM. Among the phlorotannins identified, compounds 2 and 3-5 were revealed to be non-competitive and competitive inhibitors, respectively. Furthermore, a fluorescence-quenching study of receptor-ligand binding was performed to calculate the kinetic parameters (Ksv, Kq, and K). These signal data indicated a 1:1 ratio of ligand-receptor binding. The binding conformations of the phlorotannin ligands were visually solved through molecular simulation. In conclusion, these minor phlorotannins may serve as α-glucosidase inhibitors targeted for the treatment of type 2diabetes.

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PMID: 

J Microbiol Biotechnol. 2019 Jan 28 ;29(1):11-20. PMID: 30518021

Abstract Title: 

Extract Containing Dieckol Suppresses RANKL-Induced Osteoclastogenesis via MAP Kinase/NF-κB Pathway Inhibition and Heme Oxygenase-1 Induction.

Abstract: 

, an edible marine brown alga (Laminariaceae), is a rich source of bioactive compounds such as fucoidan and phlorotannins.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-κB ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells and pit formation in bone resorption assay (＜0.05). Moreover, it suppressed RANKL-induced NF-κB 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 μg/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.

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PMID: 

Front Pharmacol. 2018 ;9:1325. Epub 2018 Nov 19. PMID: 30524282

Abstract Title: 

Therapeutic Effect ofExtract in Letrozole-Induced Polycystic Ovary Syndrome Rats.

Abstract: 

Polycystic ovary syndrome (PCOS) is an endocrinal disorder that afflicts mainly women of childbearing age. The symptoms of PCOS are irregular menstrual cycles, weight gain, subfertility and infertility. However, because the etiology is unclear, management and treatment methods for PCOS are not well established. Recently, natural substances have been used for PCOS therapy.() is a well-known natural substance that attenuates the effects of inflammation, allergies, and cancer. In this study, we investigated the effects ofextract in rats with PCOS. When rats with letrozole-induced PCOS were exposed to theextract, the regular estrus cycle was restored, similar to that in placebo rats. Hormone levels, including the levels of testosterone, estrogen, luteinizing hormone (LH), follicle stimulating hormone (FSH), and anti-Müllerian hormone (AMH), were restored to their normal states. Histological analysis revealed that the polycystic ovary symptoms were significantly decreased in the-treated rats and were comparable to those of normal ovaries. At the transcriptional and translational levels,, andlevels were markedly increased in the-treated rats with PCOS compared with the rats with letrozole-induced PCOS. These results suggest that theextract inhibits the symptoms of PCOS by restoring imbalanced hormonal levels and irregular ovarian cycles in letrozole-induced female rats.

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PMID: 

Mar Drugs. 2018 Dec 22 ;17(1). Epub 2018 Dec 22. PMID: 30583515

Abstract Title: 

Anti-Neuroinflammatory Property of Phlorotannins fromon Aβ-Induced Damage in PC12 Cells.

Abstract: 

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.is an edible brown seaweed, which has been recognized as a rich source of bioactive derivatives, mainly phlorotannins. In this study, phlorotannins including eckol, dieckol, 8,8'-bieckol were used as potential neuroprotective candidates for their anti-apoptotic and anti-inflammatory effects against Aβ-induced damage in PC12 cells. Among the tested compounds, dieckol showed the highest effect in both suppressing intracellular oxidative stress and mitochondrial dysfunction and activation of caspase family. Three phlorotannins were found to inhibit TNF-α, IL-1β and PGE₂ production at the protein levels. These result showed that the anti-inflammatory properties of our compounds are related to the down-regulation of proinflammatory enzymes, iNOS and COX-2, through the negative regulation of the NF-κB pathway in Aβ-stimulated PC12 cells. Especially, dieckol showed the strong anti-inflammatory effects via suppression of p38, ERK and JNK. However, 8,8'-bieckol markedly decreased the phosphorylation of p38 and JNK and eckol suppressed the activation of p38. Therefore, the results of this study indicated that dieckol frommight be applied as a drug candidate for the development of new generation therapeutic agents against AD.

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PMID: 

Nutrients. 2019 May 22 ;11(5). Epub 2019 May 22. PMID: 31121899

Abstract Title: 

Anti-Inflammatory Effect ofExtract onLipopolysaccharide-Stimulated Macrophages and a Periodontitis Rat Model.

Abstract: 

, an edible marine brown alga (Laminariaceae), is a rich source of phlorotannins. This study aimed to investigate the anti-inflammatory effect ofethanol extract (ECE, dieckol 10.6%,/) onlipopolysaccharide-stimulated inflammation in RAW 264.7 cells and in ligature-induced periodontitis in rats. The levels of nitric oxide (NO) and prostaglandin Ewere decreased by more than half on treatment with 100μg/mL ECE. Downregulated tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 gene expression confirmed the anti-inflammatory properties of ECE. ECE treatment upregulated heme oxygenase-1 (HO-1) expression by 6.3-fold and increased HO-1/nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling decreased nuclear factor-κB (NF-κB) translocation. ECE administration (400 mg/kg) significantly reduced gingival index, restricted tooth mobility, and prevented alveolar bone loss (

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PMID: 

Nutrients. 2019 Nov 15 ;11(11). Epub 2019 Nov 15. PMID: 31731817

Abstract Title: 

Extract Attenuates Endothelial Cell Dysfunction by Modulation of Inflammation and Brown Adipocyte Function in Perivascular Fat Tissue.

Abstract: 

It is well known that perivascular fat tissue (PVAT) dysfunction can induce endothelial cell (EC) dysfunction, an event which is related with various cardiovascular diseases. In this study, we evaluated whetherextract (ECE) and pyrogallol-phloroglucinol-6,6-bieckol (PPB), one component of ECE, could attenuate EC dysfunction by modulating diet-induced PVAT dysfunction mediated by inflammation and ER stress. A high fat diet (HFD) led to an increase in the number and size of white adipocytes in PVAT; PPB and ECE attenuated those increases. Additionally, ECE and PPB attenuated: (i) an increase in the number of M1 macrophages and the expression level of monocyte chemoattractant protein-1 (MCP-1), both of which are related to increases in macrophage infiltration and induction of inflammation in PVAT, and (ii) the expression of pro-inflammatory cytokines (e.g., tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, chemerin) in PVAT which led to vasoconstriction. Furthermore, ECE and PPB: (i) enhanced the expression of adiponectin and IL-10 which had anti-inflammatory and vasodilator effects, (ii) decreased HFD-induced endoplasmic reticulum (ER) stress and (iii) attenuated the ER stress mediated reduction in sirtuin type 1 (Sirt1) and peroxisome proliferator-activated receptor γ (PPARγ) expression. Protective effects against decreased Sirt1 and PPARγ expression led to the restoration of uncoupling protein -1 (UCP-1) expression and the browning process in PVAT. PPB or ECE attenuated endothelial dysfunction by enhancing the pAMPK-PI3K-peNOS pathway and reducing the expression of endothelin-1 (ET-1). In conclusion, PPB and ECE attenuated PVAT dysfunction and subsequent endothelial dysfunction by: (i) decreasing inflammation and ER stress, and (ii) modulating brown adipocyte function.

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