Ecklonia Cava Extract Research Articles

Ecklonia cava Ameliorates Cognitive Impairment on Amyloid β-Induced Neurotoxicity by Modulating Oxidative Stress and Synaptic Function in Institute of Cancer Research (ICR) Mice.

This study investigated the neuroprotective effect of 70% ethanol extract of Ecklonia cava (EE) in amyloid beta (Aβ)-induced cognitive deficit mice. As a result of analyzing the bioactive compounds in EE, nine compounds were identified using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In particular, the diekcol content was quantified by high-performance liquid chromatography with diode-array detection (DAD-HPLC). Biochemical analysis was performed on brain tissue to determine the mechanism of the cognitive function improvement effect of EE. The result showed that EE ameliorated learning and memory decline in behavioral tests on Aβ-induced mice. EE also attenuated oxidative stress by regulating malondialdehyde (MDA) content, reduced glutathione (GSH), and superoxide dismutase (SOD) levels. Similarly, EE also improved mitochondrial dysfunction as mitochondrial membrane potential, ATP production, and reactive oxygen species (ROS) levels. In addition, EE enhanced synapse function by modulating acetylcholine-related enzymes and synaptic structural proteins in the whole brain, hippocampus, and cerebral cortex tissues. Also, EE regulated Aβ-induced apoptosis and inflammation through the c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways. Furthermore, EE protected neurotoxicity by increasing brain-derived neurotrophic factor (BDNF) production. These results suggest that EE may be used as a dietary supplement for the prevention and treatment of Alzheimer's disease (AD).

2,7-Phloroglucinol-6,6′-bieckol from Ecklonia cava ameliorates nanoplastics-induced premature endothelial senescence and dysfunction

Nanoplastics (NPs), plastic particles ranging from 1 to 100 nm are ubiquitous environmental pollutants infiltrating ecosystems. Their small size and widespread use in various products raise concerns for human health, particularly their association with cardiovascular diseases (CVD). NPs can enter the human body through multiple routes, causing oxidative stress, and leading to the senescence and dysfunction of endothelial cells (ECs). Although there are potential natural compounds for treating CVD, there is limited research on preventing CVD induced by NPs. This study investigates the efficacy of Ecklonia cava extract (ECE) in preventing NPs-induced premature vascular senescence and dysfunction. Exposure of porcine coronary arteries (PCAs) and porcine coronary ECs to NPs, either alone or in combination with ECE, demonstrated that ECE mitigates senescence-associated β-galactosidase (SA-β-gal) activity induced by NPs, thus preventing premature endothelial senescence. ECE also improved NPs-induced vascular dysfunction. The identified active ingredient in Ecklonia cava, 2,7’-Phloroglucinol-6,6′-bieckol (PHB), a phlorotannin, proved to be pivotal in these protective effects. PHB treatment ameliorated SA-β-gal activity, reduced oxidative stress, restored cell proliferation, and decreased the expression of cell cycle regulatory proteins such as p53, p21, p16, and angiotensin type 1 receptor (AT1), well known triggers for EC senescence. Moreover, PHB also improved NPs-induced vascular dysfunction by upregulating endothelial nitric oxide synthase (eNOS) expression and restoring endothelium-dependent vasorelaxation. In conclusion, Ecklonia cava and its active ingredient, PHB, exhibit potential as therapeutic agents against NPs-induced premature EC senescence and dysfunction, indicating a protective effect against environmental pollutants-induced CVDs associated with vascular dysfunction.

Brown Algae Ecklonia cava Extract Modulates Adipogenesis and Browning in 3T3-L1 Preadipocytes through HO-1/Nrf2 Signaling.

This study explores the anti-obesity effects of the ethyl acetate extract of Ecklonia cava (EC-ETAC) on 3T3-L1 preadipocytes, focusing on its impact on adipogenesis, lipolysis, and adipose browning via the HO-1/Nrf2 pathway. Western blot analysis revealed that EC-ETAC significantly inhibited adipogenic transcription factors (PPARγ, C/EBPα, SREBP-1) and lipogenesis-related proteins (FAS, LPL). Concurrently, EC-ETAC enhanced lipolytic markers (p-AMPK, p-HSL) and adipose browning-related proteins (UCP-1, PGC-1α), indicating its role in promoting lipolysis and adipose browning. The inhibition of HO-1 by zinc protoporphyrin (ZnPP) significantly reversed these effects, underscoring the critical role of HO-1 in mediating the anti-obesity properties of EC-ETAC. Additionally, fluorescence measurements and Oil Red O staining confirmed the reduction of lipid accumulation and oxidative stress upon EC-ETAC treatment. These findings suggest that EC-ETAC exerts its anti-obesity effects by modulating the HO-1/Nrf2 pathway, which is crucial for regulating adipogenesis, lipolysis, and adipose browning. This study highlights the potential of EC-ETAC as a natural therapeutic agent for obesity management and supports further research into its clinical applications. By targeting the HO-1/Nrf2 pathway, EC-ETAC could offer a novel approach to enhancing energy expenditure and reducing fat mass, thereby improving metabolic health.

Preventive Effect of Ecklonia cava Extract on DSS-Induced Colitis by Elevating Intestinal Barrier Function and Improving Pathogenic Inflammation.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a complex gastrointestinal disorder with a multifactorial etiology, including environmental triggers, autoimmune mechanisms, and genetic predisposition. Despite advancements in therapeutic strategies for IBD, its associated mortality rate continues to rise, which is often attributed to unforeseen side effects of conventional treatments. In this context, we explored the potential of Ecklonia cava extract (ECE), derived from an edible marine alga known for its anti-inflammatory and antioxidant properties, in mitigating IBD. This study investigated the effectiveness of ECE as a preventive agent in a murine model of dextran sulfate sodium (DSS)-induced colitis. Our findings revealed that pretreatment with ECE significantly ameliorated colitis severity, as evidenced by increased colon length, reduced spleen weight, and histological improvements demonstrated by immunohistochemical analysis. Furthermore, ECE significantly attenuated the upregulation of inflammatory cytokines and mediators and the infiltration of immune cells known to be prominent features of colitis in mice. Notably, ECE alleviated dysbiosis of intestinal microflora and aided in the recovery of damaged intestinal mucosa. Mechanistically, ECE exhibited protective effects against pathogenic colitis by inhibiting the NLRP3/NF-κB pathways known to be pivotal regulators in the inflammatory signaling cascade. These compelling results suggest that ECE holds promise as a potential candidate for IBD prevention. It might be developed into a functional food for promoting gastrointestinal health. This research sheds light on the preventive potential of natural compounds like ECE in the management of IBD, offering a safer and more effective approach to combating this challenging disease.

Estrogenic active Ecklonia cava extract improves bone loss and depressive behaviour in OVX mice

Estrogenic active Ecklonia cava extract improves bone loss and depressive behaviour in OVX mice

Effect of combined UV‐thermosonication and Ecklonia cava extract on advanced glycation end‐products in soymilk

AbstractThermal treatment is used to inactivate microbes in soymilk, but it increases the amount of advanced glycation end products (AGEs). Therefore, this study examined if ultraviolet light with thermo‐sonication (UVTS) and Ecklonia cava extract (EX) could provide an alternative process to prevent AGEs formation in processed soymilk. A coiled tube UV reactor was used simultaneously with an ultrasonic generator for UVTS treatment, while an autoclave was employed for thermal treatment. UVTS treatment was examined at different temperatures and flow rates to achieve a 5‐log reduction of pre‐inoculated Escherichia coli and Salmonella typhimurium in soymilk. After confirming EX's anti‐glycation effects against fructosamine, ɑ‐dicarbonyl compounds, protein carbonyl content, and AGEs formation, it was added to soymilk before the UVTS. The ɑ‐dicarbonyl compounds (glyoxal and methylglyoxal) and AGEs (Nε‐(1‐carboxymethyl)‐l‐lysine [CML] and Nε‐(1‐carboxyethyl)‐l‐lysine [CEL]) in soymilk increased after autoclaving (AC). Compared with AC, the UVTS with .05% EX decreased glyoxal, methylglyoxal, CML, and CEL by 78%, 82%, 32%, and 59%, respectively. These results indicated that UVTS with EX could be an alternative pasteurization process for soymilk that minimizes AGEs formation.

Ecklonia cava extracts decrease hypertension-related vascular calcification by modulating PGC-1α and SOD2

Vascular calcification (VC) is induced by a decrease in sirtuin 3 (SIRT3) and superoxide dismutase (SOD)2 and increases mitochondrial reactive oxygen species (mtROS), eventually leading to mitochondrial dysfunction and phenotype alterations in vascular smooth muscle cells (VSMCs) into osteoblast-like cells in hypertension. Ecklonia cava extract (ECE) is known to increase peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) and SOD2. In this study, we evaluated the effect of ECE on decreasing VC by increasing PGC-1α which increased SOD2 activity and decreased mtROS in an in vitro VSMC model of treating serums from Wistar Kyoto (WKY), spontaneous hypertensive rats (SHRs), and ECE-treated SHRs. Furthermore, the decreasing effect of ECE on VC was evaluated with an in vivo SHR model. PGC-1α expression, SIRT3 expression, and SOD2 activity were decreased by the serum from the SHRs and increased by the serum from the ECE-treated SHRs in the VSMCs. PGC-1α silencing eliminated those increases. mtROS generation and mitochondrial DNA (mtDNA) damage increased in the SHRs but decreased with ECE. Mitochondrial fission increased in the SHRs but decreased by ECE. Mitochondrial fusion, mitophagy, and mitochondrial biogenesis were decreased in the SHRs but increased by ECE. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and calcium deposition in the medial layer of the aorta increased in the SHRs but decreased with ECE. Therefore, ECE decreases VC via the upregulation of PGC-1α and SIRT3, which increases SOD2 activity. Activated SOD2 decreases mtDNA damage and mtROS generation, which sequentially decreases NADPH oxidase activity and changes the mitochondrial dynamics, thereby decreasing VC.

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.

Dyeing Properties, UV Protection, and Deodorization of Silk Fabric Using Hot Water Extract of Ecklonia cava

To explore the potential use of Ecklonia cava as a natural dye for textiles, silk fabric was dyed with Ecklonia cava extracted by hot water under varied conditions, including temperature, duration, dye concentration, mordanting, and pH adjustment. The fabric was also evaluated for fastness, sun-protective property, and deodorization. Ecklonia cava extract was estimated by FT-IR to have polyphenol as a main functional colorant in plants, while the existence of phlorotannins through the UV-spectrum method was also confirmed. The fabric was optimized for maximum dye uptake at a temperature of 80°C for a duration of 50 minutes along all dye concentrations. The dyed fabric showed a hue of Yellow Red under all dyeing conditions while additional color tones, such as grayish and dark, were generated through mordanting and pH adjustment. Both good sunprotective properties and a positive deodorization rate were also recorded, with more than 20% (owf) Ecklonia cava extract on silk fabric. These results imply that Ecklonia cava has great potential to be used as an ecofriendly natural dye and in fashion goods with skin-health functions made of silk.

Anti-Obesity Effects of Ecklonia cava Extract in High-Fat Diet-Induced Obese Rats.

Obesity is becoming a global epidemic as a result of high-calorie food intake and unhealthy lifestyles. Different marine plants, especially brown algae (Ecklonia cava), are traditionally used to treat different health-related issues. The study was carried out to investigate the anti-obesity properties of E. cava 70% ethanol extract. To evaluate the anti-obesity effect of E. cava, both in vitro and in vivo tests were performed. E. cava suppresses pre-adipocyte 3T3-L1 differentiation in a dose-dependent manner. In HFD-induced obese rats’ models, administration of E. cava 125, 250, and 500 mg/kg significantly decreases total body weight and organs, especially liver weight, in all treatment groups. Adipose tissue weight, including subcutaneous, epididymal, peritoneal, and mesenteric adipose tissue, was markedly reduced in E. cava-treated HFD rats in dose-dependent manners. In addition, liver-related biomarkers AST, ALP, ALT, and GGT were evaluated; the lower level of liver-related biomarkers indicates no liver injury or fatty liver issue in E. cava HFD treatment groups. In addition, E. cava treatment has significant effects on the expression of adipogenic and lipogenic (PPAR-γ, FAS, LPL, and SREBP-1c) genes. Altogether, these results show the anti-obesity effect of E. cava. We concluded that E. cava could be a potential candidate for the prevention of obesity-induced by a high-fat diet.

Dieckol Reduces Muscle Atrophy by Modulating Angiotensin Type II Type 1 Receptor and NADPH Oxidase in Spontaneously Hypertensive Rats

The renin–angiotensin system is involved in the development of hypertension and sarcopenia. Increased levels of angiotensin II (Ang II) lead to upregulation of Ang II type 1 receptor (AT1R), which results in increasing reactive oxygen species (ROS) by NAD(P)H oxidase (Nox). Increased ROS led to increased helper T17 (Th17) and decreased regulatory T (Treg) cells through HIF-1α. Increased Th17 secretes more IL-17, leading to increased NF-κB and muscle atrophy. We evaluated the effect of Ecklonia cava extracts (ECE) and dieckol (DK) on attenuating muscle atrophy by decreasing AT1R and NOX activity in spontaneous hypertensive rats (SHRs). The serum levels of Ang II and expression of AT1R in the muscle were higher in SHRs than in normotensive animals of Wistar–Kyoto rats (2.4 and 1.8 times higher than WKY, respectively). The expression of AT1R decreased by ECE or DK (0.62 and 0.84 times lower than SHR, respectively). In SHRs, the expression of Nox 1, 2, and 4 were increased (1.2–1.15 times higher than WKY) but were decreased by the administration of ECE (0.8–0.9 times lower than SHR) or DK (0.7–0.9 times lower than SHR). The Nox activity was increased in SHRs (2.3 times more than WKY) and it was decreased by ECE (0.9 times lower than SHRs) and DK (0.9 times lower than SHRs). The expression of HIF-1α, a marker of Th17 (RORγt), and cytokine secreted by Th17 (IL-17) was increased in SHRs and was decreased by ECE or DK. The marker of Treg (Foxp3) and cytokine secreted from Treg cells (IL-10) was decreased in SHRs and was increased by ECE or DK. The expression of NF-κB/IL-1β/TNF-α and MuRF-1/MAFbx/atrogin-1 was increased in SHRs and these were decreased by ECE or DK. The cross-sectional area of muscle fiber was decreased in SHRs (0.7 times lower than WKY) and was increased by ECE (1.3 times greater than SHR) or DK (1.5 times greater than SHR). In conclusion, ECE or DK leads to a decreased expression of AT1R and Nox activity which modulates Th17/Treg balance and consequently, decreased muscle atrophy.

Dieckol-Attenuated High-Fat Diet Induced Muscle Atrophy by Modulating Muscular Deposition of Lipid Droplets.

An excessive fat diet induces intramuscular fat deposition that accumulates as a form of lipid droplet (LD) and leads to lipotoxicity, including muscle atrophy or decreasing muscle strength. Lipotoxicity depends on the number of LDs, subcellular distribution (intermyofibrillar, IMF, LDs or subsarcolemmal, SS), and fiber type-specific differences (type I or type II fiber) as well as the size of LD. Ecklonia cava extracts (ECE), which is known to increase peroxisome proliferator-activated receptor alpha (PPAR-α), which leads to decreasing expression level of perilipin2 (PLIN2). PLIN2 is involved in modulating the size of LDs. This study shows that ECE and dieckol could decrease PLIN2 expression and decrease the size and number of LDs in the muscle of high-fat diet (HF)-fed animals and lead to attenuating muscle atrophy. Expression level of PPAR-α was decreased, and PLIN2 was increased by HF. ECE and dieckol increased PPAR-α expression and decreased PLIN2. The diameter of LDs was increased in high-fat diet condition, and it was decreased by ECE or dieckol treatment. The number of LDs in type II fibers/total LDs was increased by HF and it was decreased by ECE or dieckol. The SS LDs were increased, and IMF LDs were decreased by HF. ECE or dieckol decreased SS LDs and increased IMF LDs. The ECE or dieckol attenuated the upregulation of muscle atrophy-related genes including Murf1, Atrogin-1, and p53 by HF. ECE or dieckol increased the cross-sectional area of the muscle fibers and grip strength, which were decreased by HF. In conclusion, ECE or dieckol decreased the size of LDs and modulated the contribution of LDs to less toxic ones by decreasing PLIN2 expression and thus attenuated muscle atrophy and strength, which were induced by HF.

Dieckol Decreases Caloric Intake and Attenuates Nonalcoholic Fatty Liver Disease and Hepatic Lymphatic Vessel Dysfunction in High-Fat-Diet-Fed Mice.

Increased inflammation is the main pathophysiology of nonalcoholic fatty liver disease (NAFLD). Inflammation affects lymphatic vessel function that contributes to the removal of immune cells or macromolecules. Dysfunctional lymphatic vessels with decreased permeability are present in NAFLD. High-fat diet (HFD) is known to increase body weight, food intake, and inflammation in the liver. Previously, it was reported that Ecklonia cava extracts (ECE) decreased food intake or weight gain, and low-calorie diet and weight loss is known as a treatment for NAFLD. In this study, the effects of ECE and dieckol (DK)—which is one component of ECE that decreases inflammation and increases lymphangiogenesis and lymphatic drainage by controlling lymphatic permeability in high-fat diet (HFD)-fed mice—on weight gain and food intake were investigated. ECE and DK decreased weight gain and food intake in the HFD-fed mice. NAFLD activities such as steatosis, lobular inflammation, and ballooning were increased by HFD and attenuated by ECE and DK. The expression of inflammatory cytokines such as IL-6 and TNF-α and infiltration of M1 macrophages were increased by HFD, and they were decreased by ECE or DK. The signaling pathways of lymphangiogenesis, VEGFR-3, PI3K/pAKT, and pERK were decreased by HFD, and they were restored by either ECE or DK. The expression of VE-cadherin (which represents lymphatic junctional function) was increased by HFD, although it was restored by either ECE or DK. In conclusion, ECE and DK attenuated NAFLD by decreasing weight gain and food intake, decreasing inflammation, and increasing lymphangiogenesis, as well as modulating lymphatic vessel permeability.

Dieckol Attenuated Glucocorticoid-Induced Muscle Atrophy by Decreasing NLRP3 Inflammasome and Pyroptosis.

Dexamethasone (Dexa), frequently used as an anti-inflammatory agent, paradoxically leads to muscle inflammation and muscle atrophy. Receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) lead to nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome formation through nuclear factor-κB (NF-κB) upregulation. NLRP3 inflammasome results in pyroptosis and is associated with the Murf-1 and atrogin-1 upregulation involved in protein degradation and muscle atrophy. The effects of Ecklonia cava extract (ECE) and dieckol (DK) on attenuating Dexa-induced muscle atrophy were evaluated by decreasing NLRP3 inflammasome formation in the muscles of Dexa-treated animals. The binding of AGE or high mobility group protein 1 to RAGE or TLR4 was increased by Dexa but significantly decreased by ECE or DK. The downstream signaling pathways of RAGE (c-Jun N-terminal kinase or p38) were increased by Dexa but decreased by ECE or DK. NF-κB, downstream of RAGE or TLR4, was increased by Dexa but decreased by ECE or DK. The NLRP3 inflammasome component (NLRP3 and apoptosis-associated speck-like), cleaved caspase -1, and cleaved gasdermin D, markers of pyroptosis, were increased by Dexa but decreased by ECE and DK. Interleukin-1β/Murf-1/atrogin-1 expression was increased by Dexa but restored by ECE or DK. The mean muscle fiber cross-sectional area and grip strength were decreased by Dexa but restored by ECE or DK. In conclusion, ECE or DK attenuated Dexa-induced muscle atrophy by decreasing NLRP3 inflammasome formation and pyroptosis.

Ecklonia cava Extract Exerts Anti-Inflammatory Effect in Human Gingival Fibroblasts and Chronic Periodontitis Animal Model by Suppression of Pro-Inflammatory Cytokines and Chemokines.

Periodontitis is one of the most common chronic inflammatory diseases. The anti-inflammatory effect of the extract from brown algae Ecklonia cava was analyzed in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGF-1), the most abundant cells in gingival tissue. The gene expressions of cyclooxygenase-2 and interleukin-6 were decreased by 78 and 50%, respectively, at 100 μg/mL Ecklonia cava extract (ECE) treatment. The gene expressions of matrix metalloproteases (MMP-2 and MMP-8) and chemokines (macrophage inflammatory protein 1-alpha and stromal cell-derived factor 1) were also significantly down-regulated by ECE treatment (p < 0.05). The increased reactive oxygen species (ROS) production in HGF-1 cells by LPS stimulation was decreased by 30% at 100 μg/mL ECE treatment. The mitogen-activated protein kinase pathway and the nuclear factor-kappa B (NF-κB) signal activated by ROS were suppressed by ECE in a dose-dependent manner. ECE treatment (400 mg/kg, 8 weeks) significantly improved alveolar bone resorption in the ligature-induced chronic periodontitis rat model. ECE supplementation also lowered elevated mRNA expression of the receptor activator of nuclear factor-kappa B (RANKL)/osteoprotegerin (OPG) in the gingival tissue (p < 0.05). Therefore, ECE mitigated gingival tissue destruction and bone resorption associated with chronic periodontitis condition.

The Effectiveness of Ecklonia Cava Kjellman Extract in Improving Menopausal Syndrome in Osteoporosis and Depression

Ecklonia cava (EC) is a natural material commonly used to decrease swelling, allergy, cancer, and sleep issues. Using EC has been reported to regulate hormones during ovarian failure in an aromatase inhibition rodent model. The aim of this study was to investigate EC’s benefits on ovariectomized female mice. Hormone replacement therapy is beneficial in menopause, but the risk of side effects increases. In the present study, alkaline phosphatase (ALP) activity and tryptophan hydroxylases (TPHs) expression were studied after the EC extracts were incorporated as elemental, phloroglucinol, eckol, dieckol, 6,6′-biekcol, and 8,8′-bieckol. In this in vivo study, the following seven groups of 10-week-old Balb/c female mice were evaluated over 8 weeks: normal mice (Sham), ovariectomized mice (OVX), ovariectomized and restraint stressed mice (OVX + R), ovariectomized and 17β-estradiol-treated mice (OVX + R + E2), ovariectomized and fluoxetine-treated mice (OVX + R + E2), and ovariectomized and EC-extract-treated mice (OVX + R + EC150 or OVX + R + EC300). The serum lipid profile, bone loss, and depressive symptoms were investigated in an ovariectomized and restraint-stressed mice model. In the in vitro models, ALP activity was dose-dependently upregulated by EC, including phloroglucinol, eckol, dieckol, 6,6′-biekcol, and 8,8′-bieckol, in RBL-2H3 cells. The transcripts of TPH1 and TPH2 were induced by EC and/or its elements (phloroglucinol, eckol, dieckol, 6,6′-biekcol, and 8,8′-bieckol) in RBL-2H3 cells. The re-uptake activity of serotonin (5-HT) was also decreased by EC and its ingredients such as phloroglucinol, eckol, dieckol, 6,6′-biekcol, and 8,8′-bieckol. In the models, the serum cholesterol and triglyceride levels were downregulated in OVX + R mice by EC treatment. The bone mineral density (BMD) was determined in EC-treated groups, and the bone metabolism markers, CTX and osteocalcin, were also reduced to normal levels. The depression experiments revealed that the immobility time was shortened in the forced-swimming test in OVX + R mice. Moreover, the serum serotonin level was promoted by EC treatment in OVX + R mice. These results showed that EC extract inhibits bone loss and depressive symptoms in a menopausal mouse model by modulating bone metabolism markers (CTX and osteocalcin) and serotonin level in OVX + R mice.

Attenuating Effects of Dieckol on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Decreasing the NLRP3 Inflammasome and Pyroptosis.

Nonalcoholic fatty liver disease (NAFLD), which promotes serious health problems, is related to the increase in the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and pyroptosis by a high-fat diet (HFD). Whether dieckol (DK), a component of Ecklonia cava extracts (ECE), attenuated NAFLD in an HFD-induced NAFLD animal model was evaluated. The expression of high mobility group box 1/Toll-like receptor 4/nuclear factor-κB, which initiated the NLRP3 inflammasome, was increased in the liver of HFD-fed animals and significantly decreased with ECE or DK administration. The expression of NLRP3/ASC/caspase-1, which are components of the NLRP3 inflammasome, and the number of pyroptotic cells were increased by HFD and decreased with ECE or DK administration. The accumulation of triglycerides and free fatty acids in the liver was increased by HFD and decreased with ECE or DK administration. The histological NAFLD score was increased by HFD and decreased with ECE or DK administration. The expression of lipogenic genes (FASN, SREBP-2, PPARγ, and FABP4) increased and that of lipolytic genes (PPARα, CPT1A, ATGL, and HSL) was decreased by HFD and attenuated with ECE or DK administration. In conclusion, ECE or DK attenuated NAFLD by decreasing the NLRP3 inflammasome and pyroptosis.

Attenuating Effects of Dieckol on Hypertensive Nephropathy in Spontaneously Hypertensive Rats.

Hypertension induces renal fibrosis or tubular interstitial fibrosis, which eventually results in end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is one of the underlying mechanisms of renal fibrosis. Though previous studies showed that Ecklonia cava extracts (ECE) and dieckol (DK) had inhibitory action on angiotensin (Ang) I-converting enzyme, which converts Ang I to Ang II. It is known that Ang II is involved in renal fibrosis; however, it was not evaluated whether ECE or DK attenuated hypertensive nephropathy by decreasing EMT. In this study, the effect of ECE and DK on decreasing Ang II and its down signal pathway of angiotensin type 1 receptor (AT1R)/TGFβ/SMAD, which is related with the EMT and restoring renal function in spontaneously hypertensive rats (SHRs), was investigated. Either ECE or DK significantly decreased the serum level of Ang II in the SHRs. Moreover, the renal expression of AT1R/TGFβ/SMAD was decreased by the administration of either ECE or DK. The mesenchymal cell markers in the kidney of SHRs was significantly decreased by ECE or DK. The fibrotic tissue of the kidney of SHRs was also significantly decreased by ECE or DK. The ratio of urine albumin/creatinine of SHRs was significantly decreased by ECE or DK. Overall, the results of this study indicate that ECE and DK decreased the serum levels of Ang II and expression of AT1R/TGFβ/SMAD, and then decreased the EMT and renal fibrosis in SHRs. Furthermore, the decrease in EMT and renal fibrosis could lead to the restoration of renal function. It seems that ECE or DK could be beneficial for decreasing hypertensive nephropathy by decreasing EMT and renal fibrosis.

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.

Antioxidant activity and laxative effects of tannin-enriched extract of Ecklonia cava in loperamide-induced constipation of SD rats.

To investigate the role of tannin-enriched extracts of Ecklonia cava (TEE) on the regulation of oxidative balance and laxative activity in chronic constipation, we investigated alterations after exposure to TEE, on constipation phenotypes, muscarinic cholinergic regulation, and oxidative stress responses in the transverse colons of SD rats with loperamide (Lop)-induced constipation. This extract contains high levels of total condensed tannin content (326.5 mg/g), and exhibited high inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. TEE treatment induced significant improvements in reactive oxygen species (ROS) production, superoxide dismutase (SOD) expression and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation in primary smooth muscles of rat intestine cells (pRISMCs) and transverse colon of constipation model. Also, Lop+TEE treated groups showed alleviated outcomes for the following: most stool parameters, gastrointestinal transit, and intestine length were remarkably recovered; a similar recovery pattern was observed in the histopathological structure, mucin secretion, water channel expression and gastrointestinal hormones secretion in the transverse colon; expressions of muscarinic acetylcholine receptors M2/M3 (mAChR M2/M3) and their mediators on muscarinic cholinergic regulation were significantly recovered. Taken together, these results provide the first evidence that TEE stimulates oxidative stress modulation and muscarinic cholinergic regulation when exerting its laxative effects in chronic constipation models.