Advances in the Study of Marine Products with Lipid-Lowering Properties.

With twice the number of cancer's deaths, cardiovascular diseases have become the leading cause of death worldwide. Atherosclerosis, in particular, is a progressive, chronic inflammatory cardiovascular disease caused by persistent damage to blood vessels due to elevated cholesterol levels and hyperlipidemia. This condition is characterized by an increase in serum cholesterol, triglycerides, and low-density lipoprotein, and a decrease in high-density lipoprotein. Although existing therapies with hypolipidemic effects can improve the living standards of patients with cardiovascular diseases, the drugs currently used in clinical practice have certain side effects, which insists on the need for the development of new types of drugs with lipid-lowering effects. Some marine-derived substances have proven hypolipidemic activities with fewer side effects and stand as a good alternative for drug development. Recently, there have been thousands of studies on substances with lipid-lowering properties of marine origin, and some are already implemented in clinical practice. Here, we summarize the active components of marine-derived products having a hypolipidemic effect. These active constituents according to their source are divided into algal, animal, plant and microbial and contribute to the development and utilization of marine medicinal products with hypolipidemic effects.

Current Research Landscape of Marine-Derived Anti-Atherosclerotic Substances.

Atherosclerosis is a chronic disease characterized by lipid accumulation and chronic inflammation of the arterial wall, which is the pathological basis for coronary heart disease, cerebrovascular disease and thromboembolic disease. Currently, there is a lack of low-cost therapeutic agents that effectively slow the progression of atherosclerosis. Therefore, the development of new drugs is urgently needed. The research and development of marine-derived drugs have gained increasing interest from researchers across the world. Many marine organisms provide a rich material basis for the development of atherosclerotic drugs. This review focuses on the latest technological advances in the structures and mechanisms of action of marine-derived anti-atherosclerotic substances and the challenges of the application of these substances including marine polysaccharides, proteins and peptides, polyunsaturated fatty acids and small molecule compounds. Here, we describe the theoretical basis of marine biological resources in the treatment of atherosclerosis.

Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial Pathway.

Fucoidan has a variety of pharmacological activities, but the understanding of the mechanism of fucoidan-induced apoptosis of colorectal cancer cells remains limited. The results of the present study demonstrated that the JNK signaling pathway is involved in the activation of apoptosis in colorectal cancer-derived HT-29 cells, and fucoidan induces apoptosis by activation of the DR4 at the transcriptional and protein levels. The survival rate of HT-29 cells was approximately 40% in the presence of 800 µg/mL of fucoidan, but was increased to 70% after DR4 was silenced by siRNA. Additionally, fucoidan has been shown to reduce the mitochondrial membrane potential and destroy the integrity of mitochondrial membrane. In the presence of an inhibitor of cytochrome C inhibitor and DR4 siRNA or the presence of cytochrome C inhibitor only, the cell survival rate was significantly higher than when cells were treated with DR4 siRNA only. These data indicate that both the DR4 and the mitochondrial pathways contribute to fucoidan-induced apoptosis of HT-29 cells, and the extrinsic pathway is upstream of the intrinsic pathway. In conclusion, the current work identified the mechanism of fucoidan-induced apoptosis and provided a novel theoretical basis for the future development of clinical applications of fucoidan as a drug.

Advances in Research on the Bioactivity of Alginate Oligosaccharides.

Alginate is a natural polysaccharide present in various marine brown seaweeds. Alginate oligosaccharide (AOS) is a degradation product of alginate, which has received increasing attention due to its low molecular weight and promising biological activity. The wide-ranging biological activity of AOS is closely related to the diversity of their structures. AOS with a specific structure and distinct applications can be obtained by different methods of alginate degradation. This review focuses on recent advances in the biological activity of alginate and its derivatives, including their anti-tumor, anti-oxidative, immunoregulatory, anti-inflammatory, neuroprotective, antibacterial, hypolipidemic, antihypertensive, and hypoglycemic properties, as well as the ability to suppress obesity and promote cell proliferation and regulate plant growth. We hope that this review will provide theoretical basis and inspiration for the high-value research developments and utilization of AOS-related products.

Advances in Studies on the Pharmacological Activities of Fucoxanthin.

Fucoxanthin is a natural carotenoid derived mostly from many species of marine brown algae. It is characterized by small molecular weight, is chemically active, can be easily oxidized, and has diverse biological activities, thus protecting cell components from ROS. Fucoxanthin inhibits the proliferation of a variety of cancer cells, promotes weight loss, acts as an antioxidant and anti-inflammatory agent, interacts with the intestinal flora to protect intestinal health, prevents organ fibrosis, and exerts a multitude of other beneficial effects. Thus, fucoxanthin has a wide range of applications and broad prospects. This review focuses primarily on the latest progress in research on its pharmacological activity and underlying mechanisms.

Biological Activities of Fucoidan and the Factors Mediating Its Therapeutic Effects: A Review of Recent Studies.

The marine acid polysaccharide fucoidan has attracted attention from both the food and pharmaceutical industries due to its promising therapeutic effects. Fucoidan is a polysaccharide that mainly consists of L-fucose and sulphate groups. Its excellent biological function is attributed to its unique biological structure. Classical activities include antitumor, antioxidant, anticoagulant, antithrombotic, immunoregulatory, antiviral and anti-inflammatory effects. More recently, fucoidan has been shown to alleviate metabolic syndrome, protect the gastrointestinal tract, benefit angiogenesis and bone health. This review focuses on the progress in our understanding of the biological activities of fucoidan, highlighting its benefits for the treatment of human disease. We hope that this review can provide some theoretical basis and inspiration for the product development of fucoidan.

Application of Fucoidan in Caco-2 Model Establishment.

The Caco-2 model is a common cell model for material intestinal absorption in vitro, which usually takes 21 days to establish. Although some studies have shown that adding puromycin (PM) can shorten the model establishment period to 7 days, this still requires a long modeling time. Therefore, exploring a shorter modeling method can reduce the experimental costs and promote the development and application of the model. Fucoidan is an acidic polysaccharide with various biological activities. Our study showed that the transepithelial electrical resistance (TEER) value could reach 600 Ω·cm2 on the fourth day after the addition of fucoidan and puromycin, which met the applicable standards of the model (>500 Ω). Moreover, the alkaline phosphatase (AKP) activity, fluorescein sodium transmittance, and cell morphology of this model all met the requirements of model establishment. Fucoidan did not affect the absorption of macromolecular proteins and drugs. The results indicate that fucoidan can be applied to establish the Caco-2 model and can shorten the model establishment period to 5 days.

Fucoidan Is Not Completely Dependent on Degradation to Fucose to Relieve Ulcerative Colitis.

Recently, fucoidan has been proposed for use as a potential anti-inflammatory drug. The purpose of this study was to investigate the mechanism of fucoidan in the treatment of ulcerative colitis. We compared the anti-inflammatory effects of fucoidan and fucose induced by dextran sulfate sodium, and the effects of fucoidan and fucose on the gut microbiota of mice. Our results showed that low-dose fucoidan significantly improved weight loss, disease activity index scores, colonic shortening, colonic histopathological damage, intestinal fatty acid binding protein 2 levels, and the expression of Occludin, Claudin-4, and Claudin-1. However, both high-dose fucoidan and fucose did not perform as well as low-dose fucoidan as described above. In addition, 16S rDNA high-throughput sequencing showed that low-dose fucoidan significantly increased the abundance of Alloprevotella, and fucose significantly increased Ruminococcaceae, but neither significantly reversed the imbalance in the gut microbiota. Therefore, we inferred that the regulation of fucoidan on colitis has a unique and complex mechanism, and it is not completely dependent on degradation to fucose to relieve ulcerative colitis, nor is it achieved only by regulating the gut microbiota. The mechanism by which fucoidan treats colitis may also include reducing inflammatory cell infiltration and increasing intestinal barrier function.

Transport Mechanisms of Polymannuronic Acid and Polyguluronic Acid Across Caco-2 Cell Monolayers.

Detailed knowledge of the intestinal transport of polymannuronic acid (PM) and polyguluronic acid (PG) is critical for understanding their biological activities. To investigate the transport in the gastrointestinal tract, PM and PG were chemically modified with tyramine and conjugated with fluorescein isothiocyanate (FITC) to synthesize FITC-PM (F-PM) and FITC-PG (F-PG) successfully. The transport mechanisms of F-PM and F-PG across the intestinal epithelial cell monolayers (Caco-2 cell monolayers) were then investigated. The results demonstrated that the transport of F-PM and F-PG into epithelial cells was time- and energy-dependent, which was mediated by the macropinocytosis pathway and the clathrin- and caveolae (or lipid raft)-mediated endocytic pathway. The transport process of F-PM and F-PG in Caco-2 cells depended on the acidification of endosomes and involved lysosomes. Tubulin mediated the transport of F-PM, but not of F-PG. Moreover, the absorption enhancer chitosan (CS) promoted the transport of F-PM and F-PG, increasing the apparent permeability coefficient (Papp) by 1.9-fold and 2.6-fold, respectively, by reversibly opening the tight junction (TJ). In summary, this study provided a comprehensive understanding of the transport of PM and PG in the small intestinal epithelial cells, which will provide a theoretical basis for the development of PM and PG with good intestinal absorption.

A peptide inhibitor of macrophage migration in atherosclerosis purified from the leech Whitmania pigra.

ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis has become a worldwide public health problem that seriously threatens human health. Leech is traditional Chinese medicine that can be utilized to treat cardiovascular disease. Based on the anti-atherosclerosis activity of leech hydrolysate, we separated and purified the leech peptide capable of inhibiting macrophage migration and studied the pathways of the anti-migration leech peptide. MATERIALS AND METHODS: The leech peptide capable of inhibiting macrophage migration that measured by cell migration assays from the leech Whitmania pigra was separated and purified by Q Sepharose FF strong alkaline anion exchange column chromatography, Superdex 30, Superdex peptide and G10 gel column chromatography. And the purity, molecular weight of the leech peptide was determined by high-performance liquid chromatography and high-resolution mass spectrometry. The pathways of anti-migration to macrophages of the leech peptide were studied by inhibitors, Western blotting and RT-PCR. RESULTS: We obtained a purified leech peptide with a sequence of EAGSAKELEGDPVAG from the leech Whitmania pigra. We also showed that the anti-migration to macrophages of the leech peptide was blocked by c-Jun N-terminal kinase (JNK) inhibitor and p38 mitogen-activated protein kinase (p38 MAPK) inhibitor. Moreover, the result of RT-PCR and Western blotting revealed that the leech peptide induced an increase in JNK, p38 phosphorylation and the transcription of mitogen-activated protein kinase kinase kinase 4 (MEKK4) and apoptosis signal-regulating kinase 2 (ASK2). These data indicated that the anti-migration to macrophages of the leech peptide occurred through JNK and p38 MAPK pathways. In addition, the results demonstrated that the leech peptide had no significant effect on the immunological activity of macrophages including phagocytic ability, lysozyme activity, and levels of expression of inflammatory factors. CONCLUSION: A sequence peptide was obtained from the hydrolysate of leech Whitmania pigra that inhibits macrophage migration.