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1.
Int J Biol Macromol ; 279(Pt 3): 135223, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39241999

RESUMEN

Laminaria digitata is a high-quality seaweed resource that is widely cultured and has good application prospects. In this study, Laminaria digitata fucoidan (LF) was extracted from Laminaria digitata, and purified using DEAE-Sepharose Fast Flow gel column to obtain four different grades. Among those, LF4 (Mw:165 kDa), mainly composed of fucose(56.80 %), had the highest total sugar (66.91 %) and sulfate (17.07 %) content. FT-RT and NMR results showed that LF4 was mainly composed of galactosylated galactofucose, and has a sulfate group attached to fucose C4. With the animal experimentation, it was revealed that hyperlipidaemic mice had significantly higher levels of TC (5.52 mmol/L), TG (2.28 mmol/L) and LDL-C (5.12 mmol/L) and significantly lower levels of HDL-C (2 mmol/L). However, LF had the efficacy in modulating the lipid metabolism disturbances induced by hyperlipidemia, as well as the ability to regulate cholesterol transport in serum. Moreover, it regulated AMPK/ACC, PPAR-α/LAXRa, Nrf2/Nqo1, TLR4/NF-κB signaling pathway genes and proteins expression in the liver. In addition, it promoted the production of beneficial short-chain fatty acids (SCFAs) while improving the composition and structure of gut microbiota, including balancing the abundance of Bacteroidota, Firmicutes, Muribaculaceae, Alloprevotella, Escherichia-Shigella, Prevotella and NK4A136. The results clearly indicated that LF4 could significantly ameliorate hyperlipidemia, suggesting its prospective application as a functional food.

2.
Int J Biol Macromol ; : 135268, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39233164

RESUMEN

Fucoidan is a sulfate-containing polysaccharide derived from the cell walls of brown algae and marine invertebrates. Fucoidan is widely used for the treatment of various diseases owing to its various biological activities. Dermatitis is an inflammatory reaction that affects the skin. The primary clinical manifestations include atopic dermatitis (AD or eczema) and various subtypes of contact dermatitis. The treatment of dermatitis primarily improves symptoms and reduces inflammation. However, owing to individual variations, some patients have a poor prognosis or symptom recurrence after conventional treatment. Owing to the excellent anti-allergic and anti-inflammatory activities of the low cost nature compound fucoidan, its therapeutic effect in inflammatory diseases has recently attracted the attention of researchers. This article summarizes and analyzes the advantages and pharmacological mechanisms of fucoidan against dermatitis to provide a reference for the selection of drugs for the treatment of dermatitis.

3.
Fish Shellfish Immunol ; : 109810, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39111606

RESUMEN

Feed terrestrial components can induce intestinal stress in fish, affecting their overall health and growth. Recent studies suggest that seaweed products may improve fish intestinal health. In this experiment, three types of feed were prepared: a basic diet (C group), a diet with 0.2% fucoidan (F group), and a diet with 3% kelp powder (K group). These diets were fed to large yellow croaker (Larimichthys crocea) over an 8-week period. Each feed was randomly assigned to three seawater cages (4.0 m × 4.0 m × 5.0 m) containing 700 fish per cage. The study assessed changes in growth and intestinal health, including intestinal tissue morphology, digestive enzyme activities, expression of immune-related genes, and bacterial community structure. Results showed that incorporating seaweed products into the diet improved the growth and quality traits of large yellow croakers and significantly enhanced their intestinal digestive capacity (P < 0.05). Specifically, the 0.2% fucoidan diet significantly increased the intestinal villus length and the activities of digestive enzymes such as trypsin, lipase, and α-amylase (P < 0.05). The 3% kelp powder diet significantly enhanced the intestinal crypt depth and the activities of trypsin and lipase (P < 0.05). Both seaweed additives significantly enhanced intestinal health by mitigating inflammatory factors. Notably, the control group's biomarkers indicated a high presence of potential pathogenic bacteria, such as Streptococcus, Pseudomonas, Enterococcus, Herbaspirillum, Neisseria, Haemophilus, and Stenotrophomonas. After the addition of seaweed additives, these bacteria were no longer the indicator bacteria, while the abundance of beneficial bacteria like Ligilactobacillus and Lactobacillus increased. Significant reductions in the expression of inflammatory factors (e.g., il-6, tnf-α, ifn-γ in the fucoidan group and il-8 in the kelp powder group) further supported these findings. Our findings suggested that both seaweed additives helped balance intestinal microbial communities and reduce bacterial antigen load. Considering the effects, costs, manufacturing, and nutrition, adding 3% kelp powder to the feed of large yellow croaker might be preferable. This study substantiated the beneficial effects of seaweed on the aquaculture of large yellow croaker, particularly in improving intestinal health. These findings advocated for its wider and more scientifically validated use in fish farming practices.

4.
Front Pharmacol ; 15: 1397761, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104391

RESUMEN

Oral leukoplakia (OLK) is the most common oral precancerous lesion, and 3%-17% of OLK patients progress to oral squamous cell carcinoma. OLK is susceptible to recurrence and has no effective treatment. However, conventional drugs have significant side effects and limitations. Therefore, it is important to identify drugs that target OLK. In this study, scavenger receptor A (SR-A) was found to be abnormally highly expressed in the oral mucosal epithelial cells of OLK patients, whereas molecular biology studies revealed that low molecular weight fucoidan (LMWF) promoted apoptosis of dysplastic oral keratinocytes (DOK) and inhibited the growth and migration of DOK, and the inhibitory effect of LMWF on OLK was achieved by regulating the SR-A/Wnt signaling axis and related genes. Based on the above results and the special situation of the oral environment, we constructed LMWF/poly(caprolactone-co-lactide) nanofiber membranes with different structures for the in-situ treatment of OLK using electrospinning technology. The results showed that the nanofiber membranes with a shell-core structure had the best physicochemical properties, biocompatibility, and therapeutic effect, which optimized the LMWF drug delivery and ensured the effective concentration of the drug at the target point, thus achieving precise treatment of local lesions in the oral cavity. This has potential application value in inhibiting the development of OLK.

5.
Nutrients ; 16(15)2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39125451

RESUMEN

Psoriasis predisposes to cardiovascular dysfunction. We investigated whether glycocalyx dietary supplement (GDS), which contains glycosaminoglycans and fucoidan, improves endothelial glycocalyx and arterial stiffness in psoriatic patients. Fifty participants with psoriasis under biological agents were randomly assigned to GDS (n = 25) or placebo (n = 25) for 4 months. We measured at baseline and at follow-up: (a) perfused boundary region (PBR) of the sublingual microvessels (range 4 to 25 µm), a marker of endothelium glycocalyx integrity; (b) carotid-femoral pulse wave velocity (PWV-Complior SP-ALAM) and augmentation index (AIx), markers of arterial stiffness and (c) psoriasis area and severity index (PASI) score. Both groups displayed a similar decrease in PASI at four months (p < 0.05), and no significant differences were found between groups (p > 0.05). Compared to the placebo, participants in the GDS showed a greater percentage reduction in PBR4-25 µm (-9.95% vs. -0.87%), PBR 4-9 µm (-6.50% vs. -0.82%), PBR10-19 µm (-5.12% vs. -1.60%), PBR 20-25 µm (-14.9% vs. -0.31%), PWV (-15.27% vs. -4.04%) and AIx (-35.57% vs. -21.85%) (p < 0.05). In the GDS group, the percentage reduction in PBR 4-25 µm was associated with the corresponding decrease in PWV (r = 0.411, p = 0.015) and AΙx (r = 0.481, p = 0.010) at follow-up. Four-month treatment with GDS improves glycocalyx integrity and arterial stiffness in patients with psoriasis. Clinical trial Identifier: NCT05184699.


Asunto(s)
Suplementos Dietéticos , Endotelio Vascular , Glicocálix , Psoriasis , Rigidez Vascular , Humanos , Glicocálix/efectos de los fármacos , Glicocálix/metabolismo , Psoriasis/tratamiento farmacológico , Masculino , Femenino , Adulto , Rigidez Vascular/efectos de los fármacos , Persona de Mediana Edad , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Método Doble Ciego , Resultado del Tratamiento
6.
Int J Pharm ; 664: 124622, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39197799

RESUMEN

Colorectal cancer (CRC) is one of the most common and challenging malignancy that needs some effective and safer chemotherapeutic agents for the treatment. In this study, anticancer agent epirubicin (Epi) was loaded in polymeric polyethylene glycol-polylactic acid-nanoparticles (mPEG-PLA-NPs) coated with a marine anti-cancer non-toxic polysaccharide fucoidan (FC), to achieve a synergistic activity against CRC. The characterization of the NPs revealed that they were spherical, monodispersed, stable, with a negative zeta potential, and exhibited good biocompatibility and controlled release. In vitro anti-cancer activity of the NPs on HCT116 cell line was found to be promising, and corroborated well with in vivo studies involving BALB/C mice injected with C26 murine cancer cells. The outcome of MTT assay demonstrated that IC50 value of free Epi was 3.72 µM, and that of non-coated and coated Epi nano-formulations was 33.67 and 10.19 µM, respectively. Higher tumor regression, better survival and reduced off-side cardiotoxicity were observed when this novel NPs formulation was used to treat tumor-bearing mice. Free FC and Epi treated mice showed 37.73 % and 61.49 % regression in tumor size, whereas there was 79.76 % and 90.34 % tumor regression in mice treated with non-coated Epi NPs and coated Epi NPs, respectively. Therefore, mPEG-PLA-FC-Epi-NPs hold a potential to be used as an effective chemotherapeutic formulation against CRC, since it exhibited better efficacy and lower toxicity.

7.
Int J Biol Macromol ; 277(Pt 3): 134397, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39097066

RESUMEN

Central nervous system (CNS) disorders have a complicated pathogenesis, and to date, no single mechanism can fully explain them. Most drugs used for CNS disorders primarily aim to manage symptoms and delay disease progression, and none have demonstrated any pathological reversal. Fucoidan is a safe, sulfated polysaccharide from seaweed that exhibits multiple pharmacological effects, and it is anticipated to be a novel treatment for CNS disorders. To assess the possible clinical uses of fucoidan, this review aims to provide an overview of its neuroprotective mechanism in both in vivo and in vitro CNS disease models, as well as its pharmacokinetics and safety. We included 39 articles on the pharmacology of fucoidan in CNS disorders. In vitro and in vivo experiments demonstrate that fucoidan has important roles in regulating lipid metabolism, enhancing the cholinergic system, maintaining the functional integrity of the blood-brain barrier and mitochondria, inhibiting inflammation, and attenuating oxidative stress and apoptosis, highlighting its potential for CNS disease treatment. Fucoidan has a protective effect against CNS disorders. With ongoing research on fucoidan, it is expected that a natural, highly effective, less toxic, and highly potent fucoidan-based drug or nutritional supplement targeting CNS diseases will be developed.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Fármacos Neuroprotectores , Polisacáridos , Polisacáridos/uso terapéutico , Polisacáridos/farmacología , Polisacáridos/química , Humanos , Animales , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos
8.
Int J Biol Macromol ; 277(Pt 3): 134517, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39111497

RESUMEN

Fucoidan-coated pH sensitive liposomes were designed for targeted delivery of gemcitabine (FU-GEM PSL) to treat pancreatic cancer (PC). FU-GEM PSL had a particle size of 175.3 ± 4.9 nm, zeta potential of -19.0 ± 3.7 mV, encapsulation efficiency (EE) of 74.05 ± 0.17 %, and drug loading (DL) of 21.27 ± 0.05 %. Cell experiments in vitro showed that FU-GEM PSL could increase the release of GEM and drug concentration, and could inhibit tumor cell proliferation by affecting the cell cycle. FU-GEM PSL entered cells through macropinocytosis and caveolin-mediated endocytosis to exert effects. Meanwhile, the expression of P-selectin was detected in human tissues, demonstrating the feasibility of targeting FU. Moreover, combined with animal experiments in vivo, FU-GEM PSL could inhibit the development of PC. Furthermore, anti-tumor experiments in vivo carried on BALB/c mice indicated that FU-GEM PSL had tumor suppression abilities and safety. Therefore, FU-GEM PSL is a promising formulation for PC therapy.


Asunto(s)
Proliferación Celular , Desoxicitidina , Gemcitabina , Liposomas , Neoplasias Pancreáticas , Polisacáridos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/química , Desoxicitidina/administración & dosificación , Animales , Polisacáridos/química , Polisacáridos/farmacología , Liposomas/química , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Ratones , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Ratones Endogámicos BALB C , Liberación de Fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Sistemas de Liberación de Medicamentos , Endocitosis/efectos de los fármacos
10.
Heliyon ; 10(14): e34316, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39130440

RESUMEN

The most prevalent form of colon cancer also ranks high among cancer-related deaths globally. Traditional chemotherapy drugs do not provide sufficient therapeutic efficacy, and advanced colon cancer demonstrates considerable resistance to chemotherapy. As an oral kinase inhibitor, sorafenib (SOR) suppresses the growth of tumour cells, the formation of new blood vessels, and the death of cancer cells. Unfortunately, sorafenib's limited bioavailability, rapid metabolism, and poor solubility have severely limited its clinical use. We developed nanoparticles targeting P-selectin and SOR, with fucoidan (FU) as a ligand. The SOR-CS-FU-NPs were developed by coating polylactide-co-glycolide nanoparticles with chitosan and FU through electrostatic interaction. The SOR-CS-FU-NPs exhibited an average particle diameter of 209.98 ± 1.25 nm and a polydisperse index (PDI) of 0.229 ± 0.022. The SOR-CS-FU nanoparticles exhibited a continuous release pattern for up to 120 h. The SOR-CS-FU nanoparticles exhibited cytotoxicity 8 times greater than free SOR in HCT116 colorectal cancer cells. The cellular absorption of Rhodamine-CS-FU-NPs was three times more than that of free Rhodamine and 19 times greater than that of Rhodamine-CS-NPs. Enhanced reactive oxygen species (ROS) generation and mitochondrial membrane potential damage were also shown in SOR-CS-FU-NPs. An investigation of cell death found that SOR-CS-FU-NPs had an apoptosis index that was 7.5 times greater than free SOR. After that, the SOR-CS-FU-NPs demonstrated a more significant inhibition of cell migration, leading to a wound closure of about 5 %. No toxicity was shown in the non-cancer VERO cell line when exposed to the developed NPs. Taken together, these results provide strong evidence that biocompatible SOR-CS-FU-NPs fabricated effective carriers for the targeted delivery of dasatinib to colorectal cancer.

11.
CNS Neurosci Ther ; 30(8): e14903, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39139089

RESUMEN

INTRODUCTION: Excessive neuroinflammation, apoptosis, glial scar, and demyelination triggered by spinal cord injury (SCI) are major obstacles to SCI repair. Fucoidan, a natural marine plant extract, possesses broad-spectrum anti-inflammatory and immunomodulatory effects and is regarded as a potential therapeutic for various diseases, including neurological disorders. However, its role in SCI has not been investigated. METHODS: In this study, we established an SCI model in mice and intervened in injury repair by daily intraperitoneal injections of different doses of fucoidan (10 and 20 mg/kg). Concurrently, primary oligodendrocyte precursor cells (OPCs) were treated in vitro to validate the differentiation-promoting effect of fucoidan on OPCs. Basso Mouse Scale (BMS), Louisville Swim Scale (LSS), and Rotarod test were carried out to measure the functional recovery. Immunofluorescence staining, and transmission electron microscopy (TEM) were performed to assess the neuroinflammation, apoptosis, glial scar, and remyelination. Western blot analysis was conducted to clarify the underlying mechanism of remyelination. RESULTS: Our results indicate that in the SCI model, fucoidan exhibits significant anti-inflammatory effects and promotes the transformation of pro-inflammatory M1-type microglia/macrophages into anti-inflammatory M2-type ones. Fucoidan enhances the survival of neurons and axons in the injury area and improves remyelination. Additionally, fucoidan promotes OPCs differentiation into mature oligodendrocytes by activating the PI3K/AKT/mTOR pathway. CONCLUSION: Fucoidan improves SCI repair by modulating the microenvironment and promoting remyelination.


Asunto(s)
Ratones Endogámicos C57BL , Polisacáridos , Recuperación de la Función , Remielinización , Traumatismos de la Médula Espinal , Animales , Polisacáridos/farmacología , Ratones , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Remielinización/efectos de los fármacos , Remielinización/fisiología , Recuperación de la Función/efectos de los fármacos , Células Precursoras de Oligodendrocitos/efectos de los fármacos , Femenino , Microambiente Celular/efectos de los fármacos
12.
Invest New Drugs ; 2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39154300

RESUMEN

Obstacles facing chemotherapeutic drugs for cancers led scientists to load Gemcitabine (GEM) into nanocarriers like liposomes, known for their nontoxicity profile and targeting capacity. The liposomal nanostructures containing GEM were coated with Fucoidan (FU) due to its anti-tumor properties by targeting cancer cells. Thus four different cationic liposomes formulations were prepared by thin-film hydration method in optimal conditions: DOTAP (formulation A); DPPC/DOTAP (4:1 molar ratio, formulation B), DPPC/DMPC/DOTAP (4:1:1 molar ratio, formulation C) and DPPC/DMPC/DOTAP/DSPE-mPEG2000 (4:1:1:0.1 molar ratio, formulation D). They were studied to identify lipid-compositions offering effective GEM-entrapment and successful coating of FU on the liposome surface. Additional qualitative characteristics, such as particle size, polydispersity index, zeta potential, stability and in vitro drug release were then evaluated. Formulation C gave the best GEM-entrapment efficiency (EE) but formed aggregates when coated with FU, giving non-homogenous large size particles then not suitable for effective delivery. It was the same situation with formulation A and B. Only the formulation D showed a good GEM-EE (> 80%) and affinity by successful coating FU from three different algae species. The PEGylated formulation D coated of FU, with regard to storage stability and drug release studies, revealed to be a promising approach on design of optimal drug delivery system.

13.
Int J Biol Macromol ; 278(Pt 3): 134186, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39173790

RESUMEN

Diabetic cognitive dysfunction (DCD) refers to cognitive impairment in individuals with diabetes, which is one of the most important comorbidities and complications. Preliminary evidence suggests that consuming sufficient dietary fiber could have benefits for both diabetes and cognitive function. However, the effect and underlying mechanism of dietary fiber on DCD remain unclear. We conducted a cross-sectional analysis using data from NHANES involving 2072 diabetics and indicated a significant positive dose-response relationship between the dietary fiber intake and cognitive performance in diabetics. Furthermore, we observed disrupted cognitive function and neuronal morphology in high-fat diet induced DCD mice, both of which were effectively restored by fucoidan supplementation through alleviating DNA epigenetic metabolic disorders. Moreover, fucoidan supplementation enhanced the levels of short-chain fatty acids (SCFAs) in the cecum of diabetic mice. These SCFAs enhanced TET2 protein stability by activating phosphorylated AMPK and improved TETs activity by reducing the ratio of (succinic acid + fumaric acid)/ α-ketoglutaric acid, subsequently enhancing TET2 function. The positive correlation between dietary fiber intake and cognitive function in diabetics was supported by human and animal studies alike. Importantly, fucoidan can prevent the occurrence of DCD by promoting TET2-mediated active DNA demethylation in the cerebral cortex of diabetic mice.

14.
Carbohydr Polym ; 343: 122448, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39174088

RESUMEN

Fucoidans, a group of high molecular weight polysaccharides derived mainly from brown algae, are characterized by their high fucose content, degree of sulfation (DS), and intra- and interspecific structural variation. Fucoidans are increasingly recognized due to various reported bioactivities, potentially beneficial for human health. To unlock their potential use within biomedical applications, a better understanding of their structure-functional relationship is needed. To achieve this, systematic bioactivity studies based on well-defined, pure fucoidans, and the establishment of standardized, satisfactory purification protocols are required. We performed a comprehensive compositional and structural characterization of crude and ultra-purified fucoidans from three kelps: Saccharina latissima (SL), Alaria esculenta (AE) and Laminaria hyperborea (LH). Further, the complement-inhibiting activity of the purified fucoidans was assessed in a human whole blood model. The purification process led to fucoidans with higher DS and fucose and lower concentrations of other monosaccharides. Fucoidans from SL and LH resembles homofucans, while AE is a heterofucan rich in galactose with comparably lower DS. Fucoidans from SL and LH showed complement-inhibiting activity in blood and blood plasma, while no inhibition was observed for AE under the same conditions. The results emphasize the importance of high DS and possibly fucose content for fucoidans' bioactive properties.


Asunto(s)
Algas Comestibles , Kelp , Laminaria , Phaeophyceae , Polisacáridos , Humanos , Inactivadores del Complemento/química , Inactivadores del Complemento/aislamiento & purificación , Inactivadores del Complemento/farmacología , Algas Comestibles/química , Fucosa/química , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , Kelp/química , Laminaria/química , Phaeophyceae/química , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Agua/química
15.
Carbohydr Polym ; 342: 122407, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39048201

RESUMEN

Nanotechnology has revolutionized the diagnosis, monitoring and treatment of biomedical diseases, in which nanocarriers have greatly improved the targeting and bioavailability of antitumor drugs. The marine natural polysaccharides fucoidan, chitosan, alginate, carrageenan and porphyran have broad-spectrum bioactivities and unique physicochemical properties such as excellent non-toxicity, biocompatibility, biodegradability and reproducibility, which have placed them as a principal focus in the nanocarrier field. Nanocarriers based on different types of marine polysaccharides are distinctive in addressing antitumor therapeutic challenges such as targeting, environmental responsiveness, drug resistance, tissue toxicity, enhancing diagnostic imaging, overcoming the first-pass effect and innovative 3D binding. Additionally, they all share the possibility of relatively easy chemical modification, while their separation into well-defined derivatives provide innovative structure-activity relationship possibilities. Liposomes, nanoparticles and polymer-micelles constructed from them can efficiently deliver drugs such as paclitaxel, gemcitabine, siRNA and others, which are widely used in radiotherapy, chemotherapy, immunotherapy, nucleic acid therapy and photothermal therapy, yet there are still infinite possibilities for innovation and exploration. This article reviews the recent advances and challenges of marine polysaccharide-based delivery systems as oncology drug nanocarriers.


Asunto(s)
Antineoplásicos , Portadores de Fármacos , Nanopartículas , Polisacáridos , Polisacáridos/química , Polisacáridos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Portadores de Fármacos/química , Humanos , Nanopartículas/química , Animales , Organismos Acuáticos/química , Alginatos/química , Quitosano/química , Neoplasias/tratamiento farmacológico , Liposomas/química , Micelas , Carragenina/química
16.
Carbohydr Polym ; 342: 122421, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39048206

RESUMEN

Although fucoidan has potential use as an anti-inflammatory agent, the specific mechanisms by which it influences signaling and immunomodulatory pathways between gut microbiota and Peyer's patches remain unclear. Therefore, the aim of this study was to investigate the therapeutic potential of fucoidan in a dextran sulfate sodium (DSS)-induced mouse model of inflammatory bowel disease (IBD) by examining the effects on gut microbiota and the underlying anti-inflammatory mechanisms. Purified fucoidan, which upon characterization revealed structural fragments comprising →3)-ß-D-Galp-(1→, →4)-α-L-Fucp-(1→, and →3)-α-L-Fucp-(1→ residues with a sulfation at position C2 was used. Treatment of the mice with fucoidan significantly alleviated the symptoms of IBD and restored the diversity of gut microbiota by enhancing the abundance of Bacteroidetes and reducing the proportion of Firmicutes. The administration of fucoidan also elevated levels of short-chain fatty acids while reducing the levels of pro-inflammatory cytokines, including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Most importantly, fucoidan attenuated the expression of integrin α4ß7/MAdCAM-1 and CCL25/CCR9, which are involved in homing intestinal lymphocytes within Peyer's patches. These findings indicate that fucoidan is a promising gut microbiota modulator and an anti-inflammatory agent for IBD.


Asunto(s)
Sulfato de Dextran , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Ganglios Linfáticos Agregados , Polisacáridos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Polisacáridos/farmacología , Polisacáridos/química , Ganglios Linfáticos Agregados/efectos de los fármacos , Ganglios Linfáticos Agregados/inmunología , Ratones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inmunología , Ratones Endogámicos C57BL , Citocinas/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química , Modelos Animales de Enfermedad , Masculino
17.
Biomater Adv ; 163: 213960, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39029207

RESUMEN

Although magnesium alloy has received tremendous attention in biodegradable cardiovascular stents, the poor in vivo corrosion resistance and limited endothelialization are still the bottlenecks for its application in cardiovascular stents. Fabrication of the multifunctional bioactive coating with excellent anti-corrosion on the surface is beneficial for rapid re-endothelialization and the normal physiological function recovery of blood vessels. In the present study, a bioactive hydrogel coating was established on the surface of magnesium alloy by copolymerization of sulfobetaine methacrylate (SBMA) and acrylamide (AM) via ultraviolet (UV) polymerization, followed by the immobilization of fucoidan (Fu). The results showed that the as-prepared multifunctional hydrogel coating could enhance the corrosion resistance and the surface wettability of the magnesium alloy surface, endowing it with the ability of selective albumin adsorption; meanwhile, it could augment biocompatibility. The following introduction of fucoidan on the surface could further improve the hemocompatibility characterized by reducing protein adsorption, minimizing hemolysis, and preventing platelet aggregation and activation. Additionally, the immobilized fucoidan promoted endothelial cell (EC) growth, as well as up-regulated the expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO) in endothelial cells (ECs). Consequently, this research paves a novel approach to developing a versatile bioactive coating for magnesium alloy surfaces and lays a foundation in cardiovascular biomaterials.


Asunto(s)
Aleaciones , Materiales Biocompatibles Revestidos , Hidrogeles , Magnesio , Polisacáridos , Stents , Polisacáridos/farmacología , Polisacáridos/química , Magnesio/química , Magnesio/farmacología , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Aleaciones/química , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Corrosión , Proliferación Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Ensayo de Materiales , Células Endoteliales/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Propiedades de Superficie , Óxido Nítrico/metabolismo
18.
Int Immunopharmacol ; 139: 112677, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39024753

RESUMEN

High-molecular-weight fucoidan (Fucoidan P), sourced from Undaria pinnatifida exhibits several health benefits, including immunomodulation. However, the mechanisms underlying the immune-enhancing effects of Fucoidan P remain unclear. Here, we investigated the immune-enhancing effects and the potential mechanisms of Fucoidan P using RAW 264.7 macrophages and cyclophosphamide (CP)-induced immunosuppression rat model. In macrophages, Fucoidan P showed dose-dependent stimulation by increasing cell proliferation, nitric oxide production, and gene expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines. These effects are mediated through the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Moreover, orally administered Fucoidan P was evaluated in immunosuppressed rats treated with CP. Fucoidan P administration increased hematological values and natural killer cell activity, and positively affected nitrite and prostaglandin E2 levels. The Fucoidan P treatment groups exhibited improved serum cytokine levels as well as splenic and intestinal cytokine mRNA expression compared to the model group. Fucoidan P also mitigated splenic damage and increased the phosphorylation of NF-κB and NF-κB inhibitor alpha (IκBα). Furthermore, Fucoidan P treatment altered the gut microbiota composition, enhancing the alpha diversity, evenness, and abundance of Bacteroidetes, which are associated with immune function. Taken together, our findings suggest that Fucoidan P exerts beneficial effects on immune function by activating NF-κB and modulating gut microbiota. These findings suggested its potential as a therapeutic agent for immune enhancement.


Asunto(s)
Ciclofosfamida , Citocinas , Microbioma Gastrointestinal , FN-kappa B , Polisacáridos , Animales , Polisacáridos/farmacología , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Células RAW 264.7 , Masculino , FN-kappa B/metabolismo , Ratas , Citocinas/metabolismo , Terapia de Inmunosupresión , Undaria/química , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Óxido Nítrico/metabolismo , Ratas Sprague-Dawley , Peso Molecular , Transducción de Señal/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/inmunología
19.
Int J Biol Macromol ; 277(Pt 2): 134226, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39074709

RESUMEN

Polysaccharides from seaweeds or macroalgae are garnering significant interest from pharmaceutical and food industries due to their bioactivities and promising therapeutic effects. Among the diverse agal polysaccharides, fucoidan is a well-documented and stands out as a well-researched sulphated heteropolysaccharide found in brown seaweeds. It primarily consists of l-fucose and sulfate ester groups, along with other monosaccharides like xylose, mannose, uronic acid, rhamnose, arabinose, and galactose. Recent scientific investigations have unveiled the formidable inhibitory prowess of fucoidan against SARS-CoV-2, offering a promising avenue for therapeutic intervention in our current landscape. Moreover, fucoidan has demonstrated remarkable abilities in safeguarding the gastrointestinal tract, regulating angiogenesis, mitigating metabolic syndrome, and fortifying bone health. Despite the abundance of studies underscoring fucoidan's potential as a vital component sourced from nature, its exploitation remains constrained by inherent limitations. Thus, the primary objective of this article is to furnish a comprehensive discourse on the structural attributes, health-enhancing properties, safety parameters, and potential toxicity associated with fucoidan. Furthermore, the discourse extends to elucidating the practical applications and developmental prospects of fucoidan as a cornerstone in the realm of functional foods and nutraceuticals.


Asunto(s)
Suplementos Dietéticos , Polisacáridos , Polisacáridos/química , Polisacáridos/farmacología , Humanos , Algas Marinas/química , SARS-CoV-2/efectos de los fármacos , Animales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Antivirales/farmacología , Antivirales/química
20.
Int J Biol Macromol ; 276(Pt 1): 133496, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38986999

RESUMEN

Dengue virus (DENV) infection poses a global health threat, leading to severe conditions with the potential for critical outcomes. Currently, there are no specific drugs available whereas the vaccine does not offer comprehensive protection across all DENV serotypes. Therefore, the development of potential antiviral agents is necessary to reduce the severity risk and interrupt the transmission circuit. The search for effective antiviral agents against DENV has predominantly focused on natural resources, particularly those demonstrating diverse biological activities and high safety profiles. Cyanobacteria and algae including Leptolyngbya sp., Spirulina sp., Chlorella sp., and Sargassum spp., which are prevalent species in Thailand, have been reported for their diverse biological activities and high safety profiles. However, their anti-DENV activity has not been documented. In this study, the screening assay was performed to compare the antiviral activity against DENV of crude polysaccharide and ethanolic extracts derived from 4 species of cyanobacteria and algae in Vero cells. Polysaccharide extracts from Sargassum spp. were the most effective in inhibiting DENV-2 infection under co-infection conditions, where the virus was exposed to the extract at the time of infection. Treatment of the extract significantly reduced the ability of DENV to bind to the host cells to 47.87 ± 3.88 % while treatment upon virus binding step had no antiviral effect suggesting the underlaying mechanism of the extract on interfering virus binding step. Fucoidan, a key bioactive substance in Sargassum polysaccharide, showed to reduce DENV-2 infection to 26.59 ± 5.01 %, 20.46 ± 6.58 % under the co-infection condition in Vero and A549 cells, respectively. In accompanied with Sargassum polysaccharide, fucoidan disturbed the virus binding to the host cells. These findings warrant further development and exploration of the Sargassum-derived polysaccharide, fucoidan, as a promising candidate for combating DENV infections.


Asunto(s)
Antivirales , Virus del Dengue , Dengue , Polisacáridos , Sargassum , Polisacáridos/farmacología , Polisacáridos/química , Virus del Dengue/efectos de los fármacos , Sargassum/química , Antivirales/farmacología , Antivirales/química , Chlorocebus aethiops , Células Vero , Animales , Dengue/tratamiento farmacológico , Dengue/virología , Humanos
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