Search Results (5,694)

Pyropia haitanensis polysaccharides have attracted growing attention for their diverse biological activities. In this study, we developed a synergistic extraction approach combining ultrasonic-assisted treatment and enzymatic hydrolysis using cellulase and pectinase. Response surface methodology (RSM) was applied to optimize the extraction conditions, which were determined as follows: 1.48% cellulase, 1.47% pectinase, 180 W ultrasonic power, and 65.9 °C temperature. Under these conditions, the polysaccharide yield reached 10.184 ± 0.27%. The crude extract was then purified through sequential DEAE Sepharose FastFlow and Sephadex G-75 chromatography, resulting in the purified fraction PPHP3. Monosaccharide analysis revealed that galactose, glucose, and glucuronic acid constituted the primary components in a molar ratio of 98.3:0.46:1.24. This polysaccharide exhibited a weight-average molecular weight of 25.208 kDa, a sulfate content of 8.64 ± 0.05%. In hypolipidemic assays using oleic acid-induced HepG2 cells, PPHP3 significantly reduced intracellular triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while simultaneously increasing HDL-C levels. These findings highlight the potential of P. haitanensis polysaccharides for hypolipidemic applications and establish a scientific foundation for their development in therapeutic and practical contexts. Full article

Recent evidence suggests that microbiota-derived porphyrins contribute to skin aging, a phenomenon termed porphyr’aging. These pro-inflammatory molecules alter the expression of genes involved in senescence, trigger melanogenesis, and decrease collagen I synthesis in skin. The aim of this study was to evaluate the anti-aging properties of an upcycled Laminaria hyperborea extract (LHE) targeting bacterial porphyrins discovered after screening. The impact of LHE on porphyrin biosynthesis and on melanogenesis and wrinkles was evaluated using in vitro and ex vivo tests and by conducting a double-blinded vs. placebo clinical trial. LHE significantly reduced coproporphyrin III production in Gram-positive skin bacteria and significantly decreased porphyrin levels in vivo at the skin surface. This activity was supported by a specific composition of LHE, comprising laminaran and mannitol. It also significantly decreased melanin content in skin explants and pigmentation in the clinical study (−5.9%). This effect was particularly pronounced in dark spots (ITA +39.9%), and the number of precursor spots also decreased (−6.9%). In addition, LHE significantly stimulated type I α-1 pro-collagen production in fibroblasts and increased collagen I and elastin expression in skin explants. These results were consistent with the clinical study, showing significant reductions in wrinkle number (−9.8%) and area (−5.8%). These findings suggest that targeting microbiota-derived porphyrins and their consequences may represent a promising approach to reduce the visible signs of aging. Full article

An unreported bicyclic sesquiterpene acid, verruculosic acid (1), was isolated together with the previously reported labdane diterpenes, (+)-agathic acid (2a) and hypoxyterpenoid A (2b), one 3-nor-2,3-seco-labdane, penioxalicin (3), and 5-carboxyphthalide (4), from a sea grass-associated fungus, Penicillium verruculosum KUFA1509. The structures of the isolated compounds were elucidated by detailed analyses of 1D and 2D NMR and HRMS data. The absolute configurations of the stereogenic carbons in 1 and 2a were established by X-ray crystallography. The crystal structure of 2a, which was obtained for the first time, was used to prove its structure and confirm its stereochemistry. The crystal structure of 3 was also obtained; however, the value of its flack parameter does not allow us to determine the absolute configuration. Compound 2b exhibited stronger inhibitory activity than the positive control, diclofenac sodium, against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, while 1 and 2a were slightly less active than the positive control. In contrast, 3 exhibited much weaker activity than 2a. Compounds 1–4 were also assayed for antibacterial activity against reference and multidrug-resistant strains, but none exhibited antibacterial activity against the tested strains. Thus, the labdane skeleton could be considered as a potential scaffold for the development of anti-inflammatory agents through NO inhibition. Full article

Floridoside (2-(α-D-galactosyl)glycerol) is a compatible solute synthesized in red algae, known for its antioxidant, immunostimulatory, anti-inflammatory, and antimicrobial properties. However, the lack of target validation has limited mechanistic insights into its bioactivity. Mitogen-activated protein kinase 13 (MAPK13), a member of the p38 mitogen-activated protein kinase (p38 MAPK) family with unique structural and functional characteristics, plays an important role in respiratory tissue remodeling, tumor progression, and immune responses, making it an attractive therapeutic target. This study identifies MAPK13 as a high-affinity target of floridoside. In vitro kinase assays validated that floridoside effectively inhibits MAPK13 with a nanomolar inhibitory concentration (IC50 = 13.59 nM), significantly outperforming the classical inhibitor BIRB-796. Unbiased molecular dynamics simulations and steered molecular dynamics simulations reveal that floridoside binds within the MAPK13 hinge region via an ATP-competitive mechanism. Binding free energy analysis combined with computational alanine scanning highlight Asp-113 as a primary interaction hotspot, stabilized by persistent hydrogen bonds with Pro-108 and Met-110. Despite stable complex formation, the flexibility of the glycosidic bond and glycerol tail may limit binding persistence. Comparative simulations with 2-α-glucosylglycerol (2αGG), a stereoisomer of floridoside, demonstrate the sensitivity of MAPK13 binding to subtle structural variations. These findings elucidate the atomistic basis for floridoside’s bioactivity and establish it as a candidate natural scaffold for the design of isoform-selective p38 inhibitors. Full article

Mussel foot proteins (Mfps) are renowned for their underwater adhesion, whereas their biotechnological potential for cutaneous wound repair remains largely underexplored. In this study, we identified and characterized a cysteine-rich mussel foot protein, Mfp6-1, from Mytilus coruscus and investigated its therapeutic potential for wound healing. Sequence analysis showed that Mfp6-1 is enriched in cysteine (11.0%) and tyrosine (~16.5%). We successfully expressed recombinant Mfp6-1 (rMfp6-1) in E. coli. Structural prediction based on the mature peptide sequence suggested that rMfp6-1 adopts a relatively compact fold containing several short β-structural elements. In vitro assays demonstrated that rMfp6-1 possesses antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and alkylation experiments suggested that cysteine residues contribute importantly to this activity. Dithio-bis-nitrobenzoic acid (DTNB)-based thiol quantification further demonstrated that rMfp6-1 contained abundant accessible free sulfhydryl groups, supporting an important contribution of cysteine-derived thiols to its antioxidant activity. Experiments on a full-thickness mouse wound model showed that rMfp6-1 treatment resulted in significantly faster wound contraction. Morphological analysis further revealed that rMfp6-1 optimizes the healing microenvironment by promoting collagen accumulation and re-epithelialization. Additionally, the treatment was found to trigger vascular endothelial growth factor (VEGF)-mediated angiogenesis, thereby improving the overall quality of the regenerated tissue. Furthermore, rMfp6-1 treatment significantly reduced interleukin-6 (IL-6) expression, suggesting that its antioxidant capacity creates a permissive microenvironment for tissue regeneration by suppressing excessive inflammation. These findings indicate that recombinant rMfp6-1 is a promising bioactive candidate for wound-healing applications. Full article

The liver is a central regulator of systemic metabolism and exhibits exceptional regenerative capacity, yet aging progressively impairs hepatic resilience through metabolic dysregulation, mitochondrial dysfunction, epigenetic instability, and chronic inflammation. Marine ecosystems constitute a vast and underexplored source of structurally diverse bioactive compounds that have evolved to modulate conserved stress response and homeostatic pathways. This review synthesizes current preclinical evidence demonstrating how marine-derived metabolites target key molecular axes implicated in liver aging, including energy sensing, redox balance, mitochondrial quality control, inflammatory signaling, and chromatin-associated regulation. Rather than focusing solely on isolated hepatoprotective effects, we frame marine bioactives within an aging biology perspective, highlighting their ability to modulate pathways associated with cellular plasticity and resilience. We further propose that this mechanistic convergence provides a theoretical framework for exploring marine compounds as potential adjunctive modulators within emerging, experimental liver rejuvenation strategies, including partial cellular reprogramming approaches that require coordinated metabolic and epigenetic control. While acknowledging that direct reversal of liver aging remains to be clinically established, integrating marine chemodiversity with contemporary aging and regenerative biology outlines a conceptual roadmap for developing liver-directed interventions targeting aging-related vulnerability as a fundamental driver of disease. Full article

Sulfated polysaccharides (SPs), biologically active macromolecules from marine and terrestrial organisms, hold significant potential in revolutionizing cancer therapy. Characterized by their unique sulfate ester groups and structural diversity, SPs exhibit a broad spectrum of bioactivities, including immunomodulation, apoptosis induction, metastasis suppression, and angiogenesis inhibition. Prominent SPs, such as fucoidan from brown algae and carrageenan from red algae, have shown remarkable anticancer properties, either as standalone agents or in synergy with conventional therapies like chemotherapy and radiotherapy. Their mechanisms of action involve targeting critical pathways such as NF-kB, VEGF, and PI3K/Akt, disrupting cancer cell proliferation, invasion, and tumor microenvironment dynamics. SPs also enhance immune system responses, reduce chemotherapy-induced side effects, and exhibit antioxidant properties, making them versatile candidates in cancer treatment. Innovations like SP-based nanoparticles are addressing bioavailability and drug delivery challenges, providing targeted and sustained therapeutic effects while minimizing off-target toxicity. Despite their promise, challenges such as structural complexity, scalability, and clinical validation hinder their widespread adoption. This review provides a comprehensive analysis of SPs’ therapeutic potential, mechanisms, and emerging applications in oncology. It emphasizes the need for advanced extraction, characterization techniques, and clinical research to unlock their full potential, paving the way for novel, efficient, and safer cancer therapies. Full article

Mitochondrial dysfunction is a major contributor to skin photoaging. Activation of the Wnt/β-catenin pathway, a key regulator of developmental processes, can improve mitochondrial abnormalities associated with pathology. Therefore, the Wnt/β-catenin pathway emerges as a key therapeutic target in the context of photoaging. Isaridin E (ISE), a marine-derived natural product with a novel structure, exhibits potent antiplatelet and anti-inflammatory activities. We sought to examine the anti-senescence effects of ISE on fibroblasts in photoaged skin. In vitro, ISE improved UVB-induced fibroblast damage in a dose-dependent manner, restoring cell viability, reducing β-galactosidase accumulation, and suppressing SASP factor production. In a photoaging mouse model, ISE markedly decreased skin thickness, increased dermal collagen expression, and reduced SASP levels in skin tissues. ISE significantly improved fibroblast energy production deficits and mitochondrial dysfunction. RNA sequencing and Western blotting demonstrated that UVB irradiation significantly suppressed Wnt/β-catenin signaling activity, whereas ISE dose-dependently restored pathway activation. Using GSK-3β-targeted siRNA, we showed that the anti-photoaging effects of ISE are mediated via the Wnt/β-catenin pathway. ISE appears to counteract photoaging by enhancing Wnt/β-catenin activity and improving mitochondrial function. Full article

The red alga Kappaphycus alvarezii is a rich source of polysaccharides, but their high molecular weight limits skin permeability and bioavailability. To address this, we employed a free-radical degradation method to produce a low-molecular-weight polysaccharide, KP-90. Evaluation in UVB-irradiated HaCaT cells and UVA-irradiated human dermal fibroblasts demonstrated that KP-90 significantly enhanced cell viability and mitigated oxidative stress by suppressing reactive oxygen species and malondialdehyde, while restoring antioxidant enzymes (SOD, CAT and GSH-Px). Furthermore, KP-90 downregulated matrix metalloproteinases (MMP-1, -3, -9) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), thereby reducing extracellular matrix degradation and inflammation. These in vitro findings were corroborated in a UVB/UVA-irradiated nude mice model, where KP-90 alleviated epidermal hyperplasia, increased collagen I and hyaluronic acid synthesis, and improved visible signs such as wrinkles and skin laxity. These findings identify KP-90 against skin photoaging and provide a strategic approach for valorization underexploited marine biomass. Full article

Skin inflammation is characterized by oxidative stress, excessive keratinocyte activation, and the overproduction of pro-inflammatory cytokines. In a previous study, we demonstrated that the hydroalcoholic extract from Posidonia oceanica leaves (POE) mitigates psoriasis-like skin inflammation in a mouse model. In the present study, we investigated the cellular mechanisms underlying these effects in human HaCaT keratinocytes. Non-cytotoxic lipopolysaccharide (LPS) stimulation reproduced key inflammatory features, including impaired cell proliferation, increased production of ROS and NO, and the upregulation of IL-1β, IL-6, TNF-α and CXCL8/IL-8. Co-treatment with POE significantly attenuated these alterations by restoring cell proliferation, suppressing oxidative stress, particularly NOS2/NO, and normalizing both cytokine expression and release. POE alone did not affect cell viability or inflammatory markers, confirming its favorable safety profile. However, POE alone induced a mild pro-apoptotic response, which may contribute to overcoming the apoptosis resistance typically observed in psoriatic keratinocytes. Overall, these findings demonstrate that POE exerts antioxidant and anti-inflammatory effects in activated keratinocytes and support its potential as a marine-derived candidate for complementary strategies in the management of psoriasis-associated inflammatory skin disorders. Full article

Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic metabolic diseases, and inhibition of α-glucosidase activity represents an effective therapeutic strategy. Chitin is the most abundant renewable polysaccharide in the ocean, with its monosaccharide being N-acetylglucosamine (NAG). To evaluate the potential of NAG glycosides as novel α-glucosidase inhibitors, three common phenolic compounds were modified via NAG glycosylation. Their inhibitory activities were assessed at both the enzymatic and cellular levels. In addition, density functional theory (DFT), molecular dynamics (MD) simulations, and molecular docking analyses were employed to systematically investigate the effects of NAG glycosylation on enzyme inhibition and the underlying mechanisms. Compared with the parent phenolic compounds, NAG glycosides exhibited significantly enhanced α-glucosidase inhibitory activity, with NAG introduction markedly improving their binding affinity to α-glucosidase. Among them, glycoside 3a displayed the optimal inhibitory effect, comparable to acarbose, and at the cellular level, its activity at high concentrations was comparable to or slightly higher than that of metformin. Circular dichroism (CD) and MD analyses indicated that glycoside 3a increased the conformational flexibility of key residues and enhanced the structural looseness of the enzyme, thereby inhibiting its activity. NAG glycosides constitute a promising class of marine-derived α-glucosidase inhibitors, warranting further structural optimization and rational design to enhance their activity and selectivity. Full article

Fucoidan, a complex sulfated polysaccharide derived from marine brown seaweeds, exhibits broad biological activities, including anticoagulant, antitumor, antiviral, anti-inflammatory and lipid-lowering effects. Fucoidan confers neuroprotection in animal models of a broad spectrum of brain disorders such as Parkinson’s disease (PD) and depression. However, the effect of fucoidan on gut-derived neuroinflammation and associated behavioral changes has been scarcely investigated. In comparison to fucoidan from other brown seaweeds, that from Fucus vesiculosus exhibited a better neuroprotective effect in vivo and more potent radical scavenging activity in vitro. Fucoidan from Laminaria japonica ameliorates behavioral disorders related to acute ulcerative colitis (UC) in aged mice. It is of interest to assess the effects of fucoidan administration on intestinal and brain inflammation in the acute colitis mouse model. Fucoidan treatment ameliorated DSS-induced intestinal pathology, reduced the inflammatory mediator expression in the gut and brain, and activated intestinal macrophages and cortical microglia in the UC mice. It also protected the intestinal mucosal barrier and blood–brain barrier as well as prevented neuronal damage, while alleviating anxiety-like behavior in UC mice. These results suggest fucoidan supplementation may help prevent brain disorders, such as depression and PD, potentially involving gut–brain axis-related mechanisms, as fucoidan suppresses gut-derived neuroinflammation. Full article

C-type lectins (CTLs) are a large family of calcium-dependent carbohydrate-binding proteins that play crucial roles in innate immunity as pattern recognition receptors. Bivalve mollusks possess exceptionally diverse and expanded repertoires of CTLs, yet a systematic review integrating their structural, functional, and regulatory aspects has been lacking. This article provides a comprehensive synthesis of current knowledge on bivalve CTLs, analyzing their biosynthesis, complex tissue-specific expression under both normal and stressed conditions, and their multifaceted roles in immune defense and other physiological processes. Our analysis consolidates data on their diverse domain architectures, phylogenetic relationships, and the variability of key motifs within their carbohydrate-recognition domains. The results demonstrate that bivalve CTLs are not only critical for pathogen recognition, agglutination, and phagocytosis but also involved in processes like nutrition, development, byssus formation and biomineralization. However, a significant finding is that the detailed carbohydrate specificity for most bivalve CTLs remains poorly characterized, often limited to monosaccharide inhibition assays. In conclusion, while the immune role of bivalve CTLs is well-established, this review underscores a critical gap in understanding their fine glycan-binding profiles. Therefore, a shift in the focus of future research towards elucidating their structure and carbohydrate specificity is required for a full understanding of their biological functions and an assessment of their biomedical potential. Full article

This study investigated the antioxidant and antiadipogenic activities of sulfated polysaccharide (SPs) from the red seaweed Gracilaria caudata. First, sulfated polysaccharide-rich extracts (SPREs) from fifteen tropical seaweeds were screened to evaluate both their chemical composition and antioxidant potential. Among all samples, G. caudata exhibited the highest total antioxidant capacity, which justified its selection for detailed characterization. Sequential acetone precipitation produced three SPs (F1.5, F2.0, and F3.0), differing in sulfate content, monosaccharide composition, and molecular weight. In vitro assays revealed that F1.5 had the highest total antioxidant capacity and strong iron-chelating activity, while F2.0 exhibited the most effective hydroxyl radical scavenger. Importantly, F1.5 was the only SP that was non-cytotoxic to non-tumor cell lines. In 3T3-L1 preadipocytes, F1.5 attenuated H₂O₂-induced oxidative stress by reducing ROS and MDA levels and restoring GSH and SOD activity, achieving effects comparable to those of quercetin. Moreover, F1.5 inhibited adipogenic differentiation in a dose-dependent manner, as evidenced by decreased Oil Red O staining and reduced glycerol release. Collectively, these findings indicate that F1.5 exerts both antioxidant and antiadipogenic activities, highlighting G. caudata as a promising natural source of bioactive polysaccharides with potential nutraceutical applications. Nonetheless, further studies are required to elucidate the molecular mechanisms underlying these effects, validate the efficacy in vivo, and assess bioavailability and safety before clinical translation can be considered. Full article