Enhancement of Immune Checkpoint Inhibitor-Mediated Anti-Cancer Immunity by Intranasal Treatment of Ecklonia cava Fucoidan against Metastatic Lung Cancer

Although fucoidan, a well-studied seaweed-extracted polysaccharide, has shown immune stimulatory effects that elicit anticancer immunity, mucosal adjuvant effects via intranasal administration have not been studied. In this study, the effect of Ecklonia cava-extracted fucoidan (ECF) on the induction of anti-cancer immunity in the lung was examined by intranasal administration. In C57BL/6 and BALB/c mice, intranasal administration of ECF promoted the activation of dendritic cells (DCs), natural killer (NK) cells, and T cells in the mediastinal lymph node (mLN). The ECF-induced NK and T cell activation was mediated by DCs. In addition, intranasal injection with ECF enhanced the anti-PD-L1 antibody-mediated anti-cancer activities against B16 melanoma and CT-26 carcinoma tumor growth in the lungs, which were required cytotoxic T lymphocytes and NK cells. Thus, these data demonstrated that ECF functioned as a mucosal adjuvant that enhanced the immunotherapeutic effect of immune checkpoint inhibitors against metastatic lung cancer.

Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

Mixture of Phlorotannin and Fucoidan from Ecklonia cava Prevents the Aβ-Induced Cognitive Decline with Mitochondrial and Cholinergic Activation

The anti-amnesic effect of a mixture (4:6 = phlorotannin:fucoidan from Ecklonia cava, P4F6) was evaluated on amyloid-beta peptide (Aβ)-induced cognitive deficit mice. The cognitive function was examined by Y-maze, passive avoidance, and Morris water maze tests, and the intake of the mixture (P4F6) showed an ameliorating effect on Aβ-induced learning and memory impairment. After the behavioral tests, superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) contents were confirmed in brain tissue, and in the results, the mixture (P4F6) attenuated Aβ-induced oxidative stress. In addition, mitochondrial activity was evaluated by mitochondrial reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic signaling pathway, and the mixture (P4F6) enhanced mitochondrial function. Furthermore, the mixture (P4F6) effectively regulated tau hyperphosphorylation by regulating the protein kinase B (Akt) pathway, and promoted brain-derived neurotrophic factor (BDNF) in brain tissue. Moreover, in the cholinergic system, the mixture (P4F6) ameliorated acetylcholine (ACh) content by regulating acetylcholinesterase (AChE) activity and choline acetyltransferase (ChAT) expression in brain tissue. Based on these results, we suggest that this mixture of phlorotannin and fucoidan (P4F6) might be a substance for improving cognitive function by effectively regulating cognition-related molecules.

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.

Prospecting the Effects on Abalone (H. discus) Growth under Low-Salinity Stress after Feeding Citrus Peel (CP) and Ecklonia cava disuse (ECD) as Feed Additives

This study addressed the effects of adding citrus peel (CP) and Ecklonia cava disuse extract (ECD) in the diet of abalones, which are a highly utilized marine species in Korea. As interest in abalone farming is increasing around the fishing community, the installation of land tanks and fish farms on the southern coast and Jeju Island in South Korea is spreading remarkably. In order to create the best opportunities for survival and reproduction, immunity to disease, and growth potential of abalones, we must consider the diet implemented in abalone farming. The survival rate of abalone has shown positive results when their diet is supplemented with CP and ECD. Our research also concluded that the addition of ECD may have a significant effect on the abalone growth and physiology.

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.