Background: Marine-derived secondary metabolites such as phlorotannins from the edible brown alga Ecklonia cava exhibit diverse bioactivities. However, their mechanisms in inflammation-associated cancer remain insufficiently understood. Methods: This study explored the anticancer potential of three major phlorotannins (dieckol, 7-phloroeckol, and 8,8′-bieckol) through network pharmacology, molecular docking, molecular dynamics simulations, and in vitro validation in SKOV3 ovarian cancer cells and tumor-associated macrophages (TAMs). Results: Computational analyses revealed stable binding of phlorotannins to IL-17RA, with 7-phloroeckol and 8,8′-bieckol preferentially engaging loop-proximal regions of the receptor, while dieckol interacted with spatially distinct residues. In SKOV3 ovarian cancer cells, phlorotannins suppressed migration and invasion by approximately 40 to 60%, accompanied by reduced MMP expression linked to IL-17RA–Act1 signaling attenuation and by increased TIMP1 expression in association with transient ERK1/2 activation. In TAMs, phlorotannins attenuated pro-tumorigenic cytokine production and polarization marker expression, indicating suppression of tumor-supportive immune activity. Conclusions: Collectively, these findings demonstrate that E. cava-derived phlorotannins exert anti-metastatic effects through dual regulation of IL-17RA/Act1 and ERK1/2 signaling pathways, offering mechanistic insight into their therapeutic potential against inflammation-driven malignancies.

SUMMARY Significant changes in seaweed communities were identified at six sites in Japan through the long‐term monitoring program ‘ Monitoring Sites 1000 .’ This study summarizes the results of 15 years of surveys conducted from 2008 to 2022. Annual nondestructive permanent quadrat observations and line‐transect surveys, carried out perpendicular to the shoreline, were used to assess species composition, coverage, and vertical distribution. Canopy‐forming seaweeds were present at all sites from 2008 to 2015; however, Ecklonia radicosa at the Satsuma‐Nagashima site on Kyushu, facing the open ocean, suddenly disappeared in 2016 and has not recovered since. As this species currently persists only in a nearby semi‐enclosed area, monitoring continues at both the disappeared and remaining locations. Similarly, Ecklonia cava and Eisenia bicyclis at the Shimoda site in central Honshu, facing the Pacific Ocean, gradually declined after 2018 and had completely disappeared by 2022. At the Shizugawa site on the Pacific coast of northern Honshu, the upward shift of Eisenia bicyclis communities to shallower depths—caused by seafloor subsidence following the 2011 earthquake—has persisted, with no recovery at the species' former deepest distribution. Saccharina japonica at the Muroran site in Hokkaido was abundant nearshore but showed considerable interannual variation offshore. At the remaining two sites, Takeno and Awaji‐Yura, located on the coasts of the Sea of Japan and the Pacific Ocean in central Honshu, respectively, Ecklonia and Sargassum communities appeared relatively stable. Nonetheless, shifts in canopy‐forming species were frequently observed, suggesting ongoing gap dynamics driven by community succession and episodic disturbances such as typhoons and heavy rainfall. Over the 15‐year period, canopy‐forming species disappeared from two of the six sites, apparently due to direct or indirect impacts of environmental change. Even at the other four sites, persistent communities were influenced by abiotic and biotic factors, underscoring the need for continued long‐term monitoring.

Cancer remains a significant global health challenge, affecting populations in both developed and developing countries. Increasing attention is being directed toward the potential of natural compounds as promising candidates in the search for effective cancer treatments. Dieckol, a marine-derived phlorotannin isolated from the brown algae Ecklonia cava, has garnered attention for its broad-spectrum bioactivities, particularly its anticancer potential. Dieckol demonstrates potent antioxidant and anti-inflammatory properties that help reduce oxidative stress and persistent inflammation, both of which are key contributors to tumor progression. It influences critical cellular processes such as apoptosis and autophagy, often triggering mitochondrial dysfunction and lysosomal impairment to induce cancer cell death. Dieckol has been shown to influence biotransformation enzymes and to restrict tumor invasion and metastasis by modulating matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and tissue inhibitors of metalloproteinases (TIMPs). In addition, it disrupts multiple oncogenic signaling cascades such as PI3K/Akt/mTOR, NF-κB, JAK/STAT3, and FAK which collectively hinder cancer cell growth, survival, motility, and angiogenesis. The aim of this review is to provide an in-depth analysis of existing studies on dieckol, emphasizing its diverse mechanisms and potential in suppressing cancer progression. It further highlights current evidence, clarifies its molecular targets, and evaluates its prospects as a promising candidate for cancer prevention and therapy.

Wild and cultivated Ecklonia cava: A comparative study of metabolites and bioactivities for industrial applications.

An atypical surface shape was observed in encrusting coral colonies of Montipora millepora. Initial assumptions on their origin focused on the presence of epibiotic intermediate habitat formers, such as coral-dwelling and -boring organisms. However, further investigations revealed their origin to also be substrate shape-related, prompted by overgrowing other foundation species. The unusual bumps stemmed from encrusting over specimens of the coral Alveopora japonica, and the forked, tube-like structures over holdfasts of the brown alga Ecklonia cava. Spatial distribution patterns and interspecific competition are briefly reviewed. Potential effects of morphological changes for Montipora species identification, as well as implications of altered topography in general, are mentioned.

The main kelp forest-forming alga Ecklonia cava (E. cava), plays an important role in coastal ecosystems of South Korea. Despite this coastal ecological importance, there is a lack of research on the prediction of macroalgal distribution. In this study, we examined the distribution of E. cava recorded since 1955 and predicted distribution changes starting from 2000, under different climate change scenarios (SSP1-1.9 and SSP5-8.5) using the species distribution model (MAXENT). It reported that E. cava has expanded its range to 38°N latitude since 2000. We found seawater temperature, primary productivity and seawater velocity were controlling factors that determine the habitat of E. cava. Under the low emissions scenario (SSP1-1.9), the habitat suitability and distribution of suitable habitats did not show significant changes. While, under the high emissions scenario (SSP5-8.5), a decline in the southern distribution and an expansion of the northern distribution was predicted. In particular, most of the current habitats of E. cava were found to have decreased habitat suitability, thus the existing population of the species in South Korea may experience a sharp decline. The results of this study can be used as a basis for developing sustainable conservation measures to maintain coastal ecosystems of rocky shore in South Korea.

Phlorotannins, bioactive compounds isolated from brown seaweeds, have garnered significant attention in recent years for their wide-ranging therapeutic properties, particularly their anti-inflammatory effects. Recent studies have identified phlorotannins as potent inhibitors of inflammatory pathways such as NF-κB, MAPK, JAK/STAT3, and NLRP3. Specifically, phlorotannins derived from seaweeds like Ecklonia cava, Ishige okamurae, and Sargassum horneri have been shown to inhibit the gene and protein expression of pro-inflammatory cytokines and other inflammatory mediators in both in vivo and in vitro conditions. Despite these promising findings, no commercial drugs derived from seaweed phlorotannins have yet been developed to treat inflammatory diseases, and reports of clinical trials remain rare, even in the context of functional food applications for chronic inflammatory conditions. To address this knowledge gap, the authors reviewed peer-reviewed research articles published in 2020 or later, focusing on the anti-inflammatory potential of phlorotannins. The insights provided in this review are expected to be valuable for industries such as functional food research groups and others involved in developing anti-inflammatory therapeutics.

Background/Objectives: Hair loss affects self-esteem, confidence, and psychological well-being. Exosomes, as molecular carriers of growth factors and active compounds, offer a promising treatment. This study evaluates the efficacy of an exosome formulation containing extracts from two known hair-regenerating plants, Ecklonia cava and Thuja orientalis (ECPE), for male pattern alopecia. Methods: A randomized controlled trial included 20 male participants with Norwood grade 2-3 androgenetic alopecia who were randomly assigned into two groups, placebo (0.9% sodium chloride) and ECPE, administered bi-weekly across four sessions. Evaluations included hair density measurements, adverse effect tracking, and self-assessments. Results: Most participants (55%) were aged 18 to 35, with 75% reporting hair loss for over a year and 80% noting scalp thinning. The hair counts showed no significant change in the placebo group from baseline to week 16 (Wilcoxon signed-rank test: V = 13.5, p = 0.163), while a significant increase was observed in the ECPE group (V = 0, p = 0.002). Between-group analysis revealed a significant difference in the hair count changes (Wilcoxon rank-sum test: W = 86.5, p = 0.006) with a large effect size (Cliff's Delta: & = 0.73, 95% CI: 0.41-0.89), with the ECPE group showing higher median hair growth (9.5, IQR = 16.88) compared to the placebo group (1.5, IQR = 3.00). A Bayesian ANCOVA, adjusted for covariates (the father's scalp hair condition, baseline hair count, and Norwood classification), showed no significant effect of these factors on the outcomes. Conclusions: These findings suggest that ECPE significantly improves hair regrowth compared to the placebo, with no notable adverse effects.

Under physiological conditions, the inflammatory response acts as a biological defense against tissue damage or infection, and is rapidly resolved once the infection is cleared. However, chronic inflammatory diseases, including inflammatory bowel disease (IBD), have become increasingly widespread in the last decades, placing a burden on the quality of life of affected people and on healthcare systems worldwide. Available drug therapies are often ineffective due to the chronic nature of these diseases, and prolonged administration of drugs can result in severe side effects for the patient or a lack of efficacy. In addition, there is the growing problem of bacterial resistance to synthetic antibiotics. Together, these factors have led to a strong research focus on the discovery of natural products capable of treating IBD. Recently, there has been a growing interest in compounds derived from marine sources, mainly algae, due to their bioactive secondary metabolites with anti-inflammatory properties well known in the literature. Based on this evidence, this review aimed to evaluate the anti-inflammatory potential of algae-derived biomolecules in IBD. In particular, interesting species from green algae (e.g., Chlorella vulgaris and Ulva pertusa), brown algae (e.g., Macrocystis pyrifera and Ecklonia cava) and red algae (e.g., Porphyra tenera and Grateloupia turuturu) are included in this review due to their proven anti-inflammatory properties. For this purpose, an extensive literature search was conducted using several databases. The results suggest that both macroalgae and microalgae have remarkable potential for IBD therapy due to the anti-inflammatory and antioxidant activities of their bioactive compounds. However, while the preclinical evidence is encouraging, further and long-term clinical studies are needed to better understand their mechanisms of action in order to determine the true efficacy of marine algae in the treatment of IBD.

Background and Objectives: Persistent exposure to airborne fine dust (FD) particles contributing to air pollution has been linked to various human health issues, including respiratory inflammation, allergies, and skin diseases. We aimed to identify potential seaweed anti-inflammatory bioactive reagents and determine their effects on systemic inflammatory responses induced by FD particles. Materials and Methods: While exploring anti-inflammatory bioactive reagents, we purified compounds with potential anti-inflammatory effects from the seaweed extracts of Ecklonia cava, Ecklonia stolonifera, and Codium fragile. Structural analyses of the purified compounds siphonaxanthin (Sx), fucoxanthin (Fx), dieckol (Dk), and phlorofucofuroeckol-A (PFF-A) were performed using NMR and LC-MS/MS. Results: Notably, these compounds, especially PFF-A, showed significant protective effects against FD-induced inflammatory responses in RAW 264.7 cells without cytotoxicity. Further investigation of inflammatory-associated signaling demonstrated that PFF-A inhibited IL-1β expression by modulating the NF-κB/MAPK signal pathway in FD-induced RAW 264.7 cells. Additionally, gene profiling revealed the early activation of various signature genes involved in the production of inflammatory cytokines and chemokines using gene profiling. Treatment with PFF-A markedly reduced the expression levels of pro-inflammatory and apoptosis-related genes and even elevated the Bmp gene families. Conclusions: These results suggested that PFF-A is a potential natural therapeutic candidate for managing FD-induced inflammatory response.

Ecklonia cava and its major compound dieckol, both natural marine products, possess antioxidant, anti-inflammatory, and metabolic-regulating effects. Zika virus (ZIKV), an arbovirus from the Flaviviridae family, is transmitted by mosquitoes and causes serious illnesses in humans. This study aimed to evaluate the anti-ZIKV potential of Ecklonia cava and dieckol. The antiviral activity of Ecklonia cava extract (ECE), prepared with 80% ethanol, was assessed in ZIKV-infected Vero E6 cells through MTT assay, plaque assay, and quantitative polymerase chain reaction (qPCR), demonstrating no cytotoxicity and a significant reduction in viral titers and ZIKV mRNA levels. In addition, ECE decreased the expression of tumor necrosis factor-α and interferon-induced protein with tetratricopeptide repeats in the ZIKV-infected cells. Dieckol, the primary active compound in ECE, exhibited potent anti-ZIKV activity, with a half maximal inhibitory concentration (IC50), value of 4.8 µM. In silico molecular docking analysis revealed that dieckol forms stable complexes with key ZIKV proteins, including the envelope, NS2B/NS3, and RNA-dependent RNA polymerase (RdRp) protein, exhibiting high binding energies of -438.09 kcal/mol, -1040.51 kcal/mol, and -1043.40 kcal/mol, respectively. Overall, our findings suggest that ECE and dieckol are promising candidates for the development of anti-ZIKV agents.

Purpose: Ecklonia cava is an edible brown alga with documented antitumor, anti-inflammatory, and antioxidant activities. This study analyzed the free radical scavenging capacities and bioactive compound profiles of E. cava extracts to provide foundational evidence for potential uses as a functional raw material in various food, health, and beauty products.Methods: The free radical scavenging activities of ethanol and distilled water extracts of E. cava were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. The total phenolic content was determined quantitatively using the Folin-Ciocalteu reagent, with gallic acid as the standard. And also, the flavonoid content was determined using aluminum chloride assay, with quercetin as the standard.Results: Extracts prepared using 100% ethanol (100 E), 50% ethanol (50 E), and distilled water (DW) all demonstrated substantial dose-dependent free radical scavenging activities, with the 100 E extract showing the highest scavenging capacity according to both DPPH and ABTS assays, followed by 50 E and DW extracts. Moreover, the 100 E extract exhibited scavenging activity roughly equivalent to the positive control ascorbic acid. The 100 E extract also possessed the highest total polyphenol and flavonoid contents.Conclusion:Ecklonia cava holds promise as a functional material for health foods, cosmetics, and natural therapeutics.

Carbon dioxide removal (CDR) potential in temperate macroalgal forests: A comparative study of chemical and biological net ecosystem production (NEP)

Steroids, which are often used to treat the inflammation associated with various skin diseases, have several negative side effects. As Ecklonia cava extract has anti-inflammatory effects in various diseases, we evaluated the efficacy of Ecklonia cava-derived extracellular vesicles (EVEs) in decreasing 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. We determined the effect of the EVEs on the TLR4/NF-κB/NLRP3 inflammasome in human keratinocytes and mouse ear skin. TPA-treated human keratinocytes showed an increased expression of TLR4 and its ligands HMGB1 and S100A8. TPA also increased the expression of (1) NF-κB; (2) the NLRP3 inflammasome components NLRP3, ASC, and caspase 1; and (3) the pyroptosis-related factors GSDMD-NT, IL-18, and IL-1β. However, the expression of these molecules decreased in the TPA-treated human keratinocytes after EVE treatment. Similar to the in vitro results, TPA increased the expression of these molecules in mouse ear skin, and EVE treatment decreased their expression. The TPA treatment of skin increased edema, redness, neutrophil infiltration, and epidermal thickness, and EVE reduced these symptoms of inflammation. In conclusion, the EVEs decreased TPA-induced skin inflammation, which was associated with a decrease in the TLR4/NF-κB/NLRP3 inflammasome.

This study examines the pharmacokinetics and bioavailability of phlorotannins from Ecklonia cava in rats following intravenous and oral administration. Known for their potent antioxidant, anti-inflammatory and many other bioactivities, these phlorotannins, particularly dieckol, 8,8'-bieckol, and phlorofucofuroeckol-A (PFF-A), were analyzed using high-performance liquid chromatography coupled with tandem mass spectrometry. Intravenous administration at 10 mg/kg allowed detectability in plasma for up to 36 h for dieckol and 8,8'-bieckol, but only 2 h for PFF-A. Oral administration at doses of 100 mg/kg and 1000 mg/kg showed limited detectability, indicating low bioavailability and rapid clearance, particularly for PFF-A. The pharmacokinetic data suggest non-linear increases in the maximum plasma concentration (Cmax) and area under the curve (AUC) with increasing doses, pointing to significant challenges in achieving systemic availability of these eckols through oral administration. This study underscores the necessity for advanced formulation strategies and alternative routes of administration to enhance systemic bioavailability. At the same time, this result also suggests their effects may be through non-systemic pathways such as gut microbiome modulation or lipid-rich tissue targeting. The findings lay a crucial foundation for the further development of Ecklonia cava phlorotannins as therapeutic agents, offering insights into their pharmacokinetic behavior and informing enhancements in future clinical utility.

Alzheimer’s Disease (AD) is a gradually worsening neurodegenerative condition characterized by the build-up of beta-amyloid proteins, resulting in a decline in cognitive abilities. β-site amyloid precursor protein cleaving enzyme-1 (BACE1) is known to play a role in the formation of beta-amyloid plaques. Thus, theoretically, inhibiting BACE1 can potentially prevent and slow down the accumulation of these plaques. This study is a literature review that compiles data from various research examining the inhibitory effects of compounds from marine organisms on the BACE1 enzyme. A comprehensive analysis was conducted on the available literature to evaluate the potential of these compounds. 19 marine organisms and 40 compounds were identified with low IC50 values, five compounds with notably low IC50 values were identified: (1) 8,8’-Bieckol [1.62 µM] from Ecklonia cava, (2) Phlorofucofuroeckol A [2.13 µM] and (3a) Dieckol [2.21 µM] from Eisenia bicyclis, (4) bis-(2,3,6-tribromo-4,5-dihydroxybenzyl) ether [2.32 µM] from Symphyocladia latiuscula, (3b) another Dieckol [2.34 µM] also from Ecklonia cava and (5) Heparan sulfate [2.89 µM] from Portunus pelagicus. These findings underscore the therapeutic potential of marine compounds as BACE1 inhibitors for AD. However, further research is needed to explore their bioavailability and clinical efficacy for practical application in preventing and treating Alzheimer’s Disease.

Natural deep eutectic solvents (NADES) are promising green and sustainable solvents for efficient extraction of bioactive compounds. We employed ultrasound-assisted extraction (UAE) to extract dieckol from Ecklonia cava (EC) using choline chloride-based NADES. Eight different NADES (comprising sugars, alcohols, and organic acids) and a conventional solvent were screened to select the best eutectic solvent for dieckol extraction. Among the organic acid-based NADES, choline chloride–acetic acid (CCAC; 1:1 molar ratio with a 50% [v/v] water content) exhibited a higher dieckol content (31.45 mg/g) than other NADES and ethanol. Second-order kinetic modeling was applied using CCAC with varying water content (40–80%, v/v) to confirm the extraction efficiency and underlying mechanism. The kinetic model showed that CCAC with 40% water content (v/v) exhibited the highest capacity (Ce=29.67 mg/g), while CCAC with 60% water content (v/v) yielded a superior extraction rate constant (k=0.12 mg/g min). Moreover, the dieckol extract displayed potent DPPH and ABTS+ antioxidant activities. Furthermore, structural and viscosity changes between the synthesized CCAC with and without water addition were compared. Our study proposes an eco-friendly and efficient extraction alternative for the extraction of dieckol from EC using NADES.

Method development and validation of phloroglucinol and dieckol in Ecklonia cava using HPLC-DAD.

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