This study was carried out explore the mechanism underlying the inhibition of platelet activation by kelp fucoidans in deep venous thrombosis(DVT)mouse.In the control and sham mice,the walls of deep vein were regular ...This study was carried out explore the mechanism underlying the inhibition of platelet activation by kelp fucoidans in deep venous thrombosis(DVT)mouse.In the control and sham mice,the walls of deep vein were regular and smooth with intact intima,myometrium and adventitia.The blood vessel was wrapped with the tissue and there was no thrombosis in the lumen.In the DVT model,the wall was uneven with thicken intima,myometrium and adventitia.After treated with fucoidans LF1 and LF2,the thrombus was dissolved and the blood vessel was recanalized.Compared with the control group,the ROS content,ET-1 and VWF content and the expression of PKC-βand NF-κB in the model were significantly higher(P<0.05);these levels were significantly reduced following treatments with LF2 and LF1.Compared with H_(2)O_(2)treated-HUVECs,combined LF1 and LF2 treatment resulted in significant decrease in the expression of PKC-β,NF-κB,VWF and TM protein(P<0.05).It is clear that LF1 and LF2 reduces DVT-induced ET-1,VWF and TM expressions and production of ROS,thus inhibiting the activation of PKC-β/NF-κB signal pathway and the activation of coagulation system and ultimately reducing the formation of venous thrombus.展开更多
The prevalence of obesity has increased and is a health concern worldwide.Due to the concerns regarding synthetic anti-obesity treatments,nowadays natural products become a trend.Previous studies proved that there is ...The prevalence of obesity has increased and is a health concern worldwide.Due to the concerns regarding synthetic anti-obesity treatments,nowadays natural products become a trend.Previous studies proved that there is a potential to use marine algae as anti-obesity agents.Therefore,in this study,the lipid inhibitory effect of crude polysaccharide of amyloglucosidase-assisted hydrolysate from Sargassum thunbergii(STAC)and its fucoidan fractions(STAFs)on 3T3-L1 cells and high-fat diet(HFD)-induced obese mice were investigated.According to the results,the STAF3,showed the highest xylose content and exhibited significant inhibitory effects on lipid accumulation by downregulating adipogenic and lipogenic proteins in 3T3-L1 cells.Furthermore,oral supplementation with STAC significantly declined gain in body weight and fat weight,and serum lipid contents in an HFD-induced obesity mouse model.Structural and chemical characterizations demonstrated that puritied STAF3 has consistent surface morphology and small particle size,with similar structural characteristics as commercial fucoidan.Together,these results indicate that STAC and purified STAF3 from Sargassum thunbergia is a potent source to develop as ananti-obesity agents or functional food products to counter obesity.展开更多
Fucoidan,a sulfate polysaccharide obtained from brown seaweed,has various bioactive properties,including anti-inflammatory,anti-cancer,anti-viral,anti-oxidant,anti-coagulant,anti-thrombotic,anti-angiogenic,and anti-He...Fucoidan,a sulfate polysaccharide obtained from brown seaweed,has various bioactive properties,including anti-inflammatory,anti-cancer,anti-viral,anti-oxidant,anti-coagulant,anti-thrombotic,anti-angiogenic,and anti-Helicobacter pylori properties.However,the effects of low-molecular-weight fucoidan(LMW-F)on melanoma cell lines and three dimensional(3D)cell culture models are not well understood.This study aimed to investigate the effects of LMW-F on A375 human melanoma cells and cryopreserved biospecimens derived from patients with advanced melanoma.Ultrasonic wave was used to fragment fucoidan derived from Fucus vesiculosus into smaller LMW-F.MTT and live/dead assays showed that LMW-F inhibited cell proliferation in both A375 cells and patientderived melanoma explants in a 3D-printed collagen scaffold.The PTEN/AKT pathway was found to be involved in the anti-melanoma effects of fucoidan.Western blot analysis revealed that LMW-F reduced the phosphorylation of Bcl-2 at Thr 56,which was associated with the prevention of anti-apoptotic activity of cancer cells.Our findings suggested that LMW-F could enhance anti-melanoma chemotherapy and improve the outcomes of patients with melanoma resistance.展开更多
The brown seaweed,Sacchairna japonica,has been used in traditional Chinese medicine for over one thousand years.Oral administration of fucoidan or low molecular weight fucoidan(LMWF)from S.japonica could ameliorate ki...The brown seaweed,Sacchairna japonica,has been used in traditional Chinese medicine for over one thousand years.Oral administration of fucoidan or low molecular weight fucoidan(LMWF)from S.japonica could ameliorate kidney dysfunction in chronic kidney diseases and inhibit diabetic vascular complications.In many studies,LMWF was found to be more potent than fucoidan with high molecular weight.However,the pharmacokinetics of LMWF still remains unclear.The purpose of the research is to compare the pharmacokinetics of fucoidan with high molecular weight(136 kDa)with that low molecular weight(9.5 kDa)after oral administration to ICR mice.Since fucose is the main and representative monosaccharide of fucoidans,we evaluate the pharmacokinetics of fucoidan and LMWF by determining the fucose concentration in mice serum.Both fucoidan and LMWF were absorbed following oral administration.Fucoidan and LMWF were provided to mice by oral administration with 60 mg/kg and the maximum Concentration(C_(max))was found at 2.5 h(0.66±0.32 mg/L)for Fucoidan and 1.5 h(1.01±0.56 mg/L)for LMWF,respectively.It seems that LMWF had a higher area under the curve(AUC_(0–t))and was absorbed more quickly than fucoidan.The estimated bioavailability of LMWF was28.3%in the mice treated with a single dose of 30 mg/kg.In addition,LMWF was found widely spreaded into different tissues following oral administration and the highest concentration was found in kidney at 19.93±7.02μg/g.In this study,we first studied the pharmacokinetics of LMWF,in order to help to understand the function of LMWF.And our results shed light on the potential of development of drugs based on LMWF.展开更多
Objective:To study the preventive effect of fucoidan on non-alcoholic fatty liver disease induced by high fat diet.Methods:The experimental mice were randomly divided into three groups:control group,high-fat diet grou...Objective:To study the preventive effect of fucoidan on non-alcoholic fatty liver disease induced by high fat diet.Methods:The experimental mice were randomly divided into three groups:control group,high-fat diet group and fucoidan intervention group.The control group was fed a standard diet,and the other two groups were fed a high-fat diet.The control group and the high-fat diet group were given normal saline intragastric administration every day,and the intervention group was given intragastric administration of fucoidan polysaccharide solution at a dose of 100 mg∙kg^(-1)∙d^(-1) once a day for continuous intervention for 12 weeks.After the last intragastric administration for 12 h,the body weight and liver weight of each group of mice were measured,and the liver index was calculated.The contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC)and triglyceride(TG)in liver tissues of mice in each group were detected by biochemical kit.Hematoxylin-eosin staining(HE)was used to compare the pathological morphological changes of liver tissue in each group.The contents of inflammatory factor interleukin-6(IL-6),tumor necrosis factor(TNF-α)and oxidative stress index malondialdehyde(MDA),and the activities of glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)in liver tissues of mice in each group were determined.Results:Compared with the control group,the body weight and liver index of mice receiving high fat diet increased significantly(P<0.01).In addition,the contents of TG,TC,AST and ALT in liver tissue of high-fat diet group were significantly increased compared with that of control group(P<0.01).The liver tissue of mice in the high-fat diet group also showed significant pathological changes,accompanied by increased expression of inflammatory factors and a significant increase in oxidative stress response.However,compared with the mice in the high-fat diet group,the above indexes were significantly improved in the liver tissue of the mice treated with fucoidan(P<0.01).Conclusion:Fucoidan can inhibit liver lipid deposition,liver inflammation and oxidative stress induced by high fat diet.展开更多
AIM:To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells.METHODS:In Caco-2 cell monolayer models,the disruption of barrier function by oxid...AIM:To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells.METHODS:In Caco-2 cell monolayer models,the disruption of barrier function by oxidative stress is mediated by H2O2.The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance(TER)and permeability was estimated by measuring the paracellular transport of FITC-labeled4-kDa dextran(FD4).The protective effects of fucoidan on epithelial barrier functions on polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux.The expression of tight junction(TJ)proteins was assessed using reverse-transcription polymerase chain reaction(RT-PCR)and immunofluorescence staining.RESULTS:Without H2O2treatment,fucoidan significantly increased the TER compared to control(P<0.05),indicating a direct enhancement of intestinal epithelial barrier function.Next,H2O2disrupted the epithelial barrier function in a time-dependent manner.Fucoidan prevented the H2O2-induced destruction in a dosedependent manner.Fucoidan significantly decreased H2O2-induced FD4 flux(P<0.01),indicating the prevention of disruption in paracellular permeability.RTPCR showed that Caco-2 cells endogenously expressed claudin-1 and-2,and occludin and that H2O2reduced the mRNA expression of these TJ proteins.Treatment with fucoidan attenuated the reduction in the expressions of claudin-1 and claudin-2 but not occludin.Immunofluorescence staining revealed that the expression of claudin-1 was intact and high on the cell surface.H2O2disrupted the integrity of claudin-1.Treatment with fucoidan dramatically attenuated the expression of claudin-1.CONCLUSION:Fucoidan enhanced intestinal epithelial barrier function by upregulating the expression of claudin-1.Thus,fucoidan may be an appropriate therapy for the treatment of inflammatory bowel diseases.展开更多
Fucoidan, a polysaccharide containing abundant fucose and sulfate ester group, was prepared from Laminaria japonica. In order to obtain fucoidan-degrading enzyme, bacteria capable of degrading fucoidan were screened f...Fucoidan, a polysaccharide containing abundant fucose and sulfate ester group, was prepared from Laminaria japonica. In order to obtain fucoidan-degrading enzyme, bacteria capable of degrading fucoidan were screened from kelp. A bacterial strain named RC2-3 was obtained, which degraded fucoidan by the maximum extent of 54% ± 1.3%, the highest among all bacterial isolates. High-performance size exclusion chromatography(HPSEC) showed that the molecular weight of fucoidan was gradually reduced by RC2-3 with culturing time, suggesting the production of fucoidan-degrading enzyme by RC2-3. Phylogenetic analysis of partial 16S ribosomal RNA gene(16S rDNA) sequence showed that RC2-3 belonged to the family Flavobacteriaceae. However, it showed different physiological and biochemical characteristics from the known Flavobacteriaceae members producing fucoidan-degrading enzyme, thus RC2-3 was proposed to be a new member of this family.展开更多
In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence ima...In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy(PDT) to induce the com-plete death of cancer cells. A CFN-gel has nanomolar a nity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention e ect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar a nity for the vascular endothelial growth factor, it also provides a significant anti-tumor e ect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high e cacy and specificity.展开更多
In Japan, S-1 plus cisplatin has become a standard regimen for the treatment of unresectable advanced gastric cancer;however, many patients are unable to continue effective chemotherapy because of the regimen’s sever...In Japan, S-1 plus cisplatin has become a standard regimen for the treatment of unresectable advanced gastric cancer;however, many patients are unable to continue effective chemotherapy because of the regimen’s severe side effects. Thus, control of drug toxicity is key to prolonging patient survival. Fucoidan is a major sulfated polysaccharide found in brown seaweeds and has a wide range of biological activities. In the present study, we analyzed the effect of fucoidan on suppressing the toxicity of chemotherapy drugs. Twenty-four patients with unresectable advanced gastric cancer underwent treatment with S-1 plus cisplatin and were randomly allocated into a fucoidan treatment group (n = 12) or a control group without fucoidan treatment (n = 12). The study results demonstrated that fucoidan controlled the occurrence of fatigue during chemotherapy and patients could continue chemotherapy for longer time periods by maintaining the patients’ favorable nourishment status. As a result, the survival of patients with fucoidan treatment was longer than that of patients without fucoidan. Thus, fucoidan should be included as a key food supplement for patients with gastrointestinal carcinomas who are suffering from the adverse side effects of chemotherapy.展开更多
[Objectives] The research aimed to optimize extraction process of fucoidan from Sargassum fusiforme( FSF) and study its moisturizing performance. [Methods]Extracting condition of FSF by cellulase hydrolysis-ultrasonic...[Objectives] The research aimed to optimize extraction process of fucoidan from Sargassum fusiforme( FSF) and study its moisturizing performance. [Methods]Extracting condition of FSF by cellulase hydrolysis-ultrasonic assisted extraction method was optimized. The influences of solvent p H,enzyme dosage,extraction temperature,cellulose hydrolysis time,ultrasonication time,and the ratio of material to liquid on FSF were investigated by single factor and orthogonal experiments. [Results] The optimum extraction conditions were as followings:p H,4. 5; enzyme dosage,1%; extraction temperature,40℃; cellulose hydrolysis time,2 h; ultrasonic time,15 min; and the ratio of material to liquid,1∶ 10( g∶ m L). Under the optimal condition,the extraction yield of FSF was 8. 50%,RSD = 2. 74%. The short-time hygroscopicity( within 8 h) of crude extract of fucoidan from S. fusiforme( CEFSF) was better than glycerin,butanediol,and sodium alginate,and the moisture retention capacity of 1% CEFSF aqueous solution was better than 1% butanediol or 1% sodium alginate,and was equal to 5% glycerin under relative humidity of 43% and 81%. The determination results of skin moisture content and transepidermal water loss rate( TEWL)showed that: 5% CEFSF solution had good moisturizing effect. [Conclusions]The research could provide certain reference for deep development of S. fusiforme.展开更多
Obesity is an escalating global pandemic posing a serious threat to human health.The intervention therapy using weight-reducing drugs,accompanied by lifestyle modification,is a strategy for the treatment of obesity.In...Obesity is an escalating global pandemic posing a serious threat to human health.The intervention therapy using weight-reducing drugs,accompanied by lifestyle modification,is a strategy for the treatment of obesity.In the present study,we explored the role of fucoidan,a seaweed compound,on high-fat diet(HFD)-induced obesity in mice.We found that fucoidan treatment significantly reduced the body fat and caused redistribution of visceral and subcutaneous fat in HFD-fed mice.Meanwhile,fucoidan treatment inhibited adipocyte hypertrophy and inflammation in adipose tissue.Collectively,these results suggest that fucoidan may be a promising treatment for obesity and obesity-induced complications.展开更多
Fucoidan is a sulfated polysaccharide that is primarily extracted from brown seaweeds which has been broadly studied in recent years due to its numerous biological properties, including anticoagulant, antithrombotic, ...Fucoidan is a sulfated polysaccharide that is primarily extracted from brown seaweeds which has been broadly studied in recent years due to its numerous biological properties, including anticoagulant, antithrombotic, antitumor, and antiviral activities. In this study, fucoidan was evaluated against clinic isolated methicillin-resistant Staphylococcus aureus (MRSA) 1 - 20, either alone or with antibiotics, via broth dilution method and checkerboard and time kill assay. Minimum inhibitory concentrations (MICs)/Minimum bactericidal concentrations (MBCs) values for the fucoidan against all the tested bacteria ranged between 64 - 512/256 - 2048 microg/mL, for ampicillin 32 - 1024/64 - 1024 microg/mL and for oxacillin 8 - 64/16 - 256 microg/mL respectively. Furthermore, the MIC and MBC were reduced to one half-eighth as a result of the combination of the fucoidan with antibiotics. 2 - 6 hours of treatment with 1/2 MIC of fucoidan with 1/2 MIC of antibiotics resulted from an increase of the rate of killing in units of CFU/mL to a greater degree than was observed with alone. These results suggest that fucoidan could be employed as a natural antibacterial agent against multi-drug bacteria.展开更多
OBJECTIVE To investigate the protective effect against diabetes cardiovascular complications of low molecular weight fucoidan(LMWF)from L.japonica in Qindao, China. METHODS LMWF(50,100 and 200mg·kg-1·d-1)or ...OBJECTIVE To investigate the protective effect against diabetes cardiovascular complications of low molecular weight fucoidan(LMWF)from L.japonica in Qindao, China. METHODS LMWF(50,100 and 200mg·kg-1·d-1)or probucol(100mg·kg-1·d-1)were given orally to Goto-Kakizaki type 2 diabetic rats for 12 weeks.Basal blood pressure,acetylcholine-or flow-mediated relaxation of mesenteric and paw arteries,endothelium-dependent dilation of aorta,eNOS phosphorylation and NO production were measured using laser Doppler flowmetry,force myograph,HE staining,Western blot and an NO assay,respectively.The establishment of diabetic cardiomyopathy(DCM)model and were evaluated by echocardiography and isolated heart perfusion.Ventricle staining with HE or Sirius red was performed to investigate the structural changes in myocardium.Oxidative stress and apoptosis were evaluated by enzyme activities,protein expressions and cell stainings in both myocardial tissues and cultured cardiomyocytes.RESULTS In aorta,LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta,as well as mesenteric and paw arteries in diabetic rats.In addition,the reduction in endothelial nitric oxide synthase(eNOS)phosphorylation at Ser1177,eNOS expression and NO production due to diabetes were partially reversed by LMWF treatment.However,probucol,a lipid-modifying drug with antioxidant properties,displayed only mild effects.Moreover,LMWF induced,in a dose-dependent manner,endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta,and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells.On DCM,LMWF has a beneficial effect by enhancing myocardial contractility and mitigating cardiac fibrosis as well as the production of reactive oxygen species(ROS)and myocyte apoptosis in diabetic hearts.CONCLUSION These data demonstrate for the first time that fucoidan protects vasoendothelial and cardiac function against diabetic injury in type 2diabetes rats via,at least in part,preservation of eNOS function,amelioration of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis.Fucoidan is therefore a potential candidate drug for protection of endothelium and heart in diabetic cardiovascular complications.展开更多
Marine macroalgal sulfated fucose-containing polysaccharides,like fucoidan,have drawn significant attention due to their biotechnological potentials,such as anti-cancer,antioxidant,and anti-cholinesterase activities.T...Marine macroalgal sulfated fucose-containing polysaccharides,like fucoidan,have drawn significant attention due to their biotechnological potentials,such as anti-cancer,antioxidant,and anti-cholinesterase activities.The fucoidan derived from brown macroalgae Sargassum angustifolium species(FSA)was investigated for its cytotoxic effects and alterations in cell proliferation,and cell cycle-related gene expression in the present study occurred on NB4 cell line.The results showed that FSA would induce p53,p21,pro-apoptotic genes and increase expression of the p15 gene as a cell arrest marker.Also,FSA inhibited the anti-apoptotic effect of the Bcl-2 gene and decreased dnmt-1 gene expression.FSA significantly exhibited potent 2,2-diphenyl-1-picrylhydrazyl(DPPH)radical scavenging activity(p<0.05)with an IC_(50) value of 0.157 mg/mL and showed moderate anti-acetylcholinesterase activity with an IC_(50) value of 1.20μg/mL.These results indicated the potential of FSA for the development of therapeutic or preventive agents of cancer and Alzheimer’s disease mainly through cytotoxic effect and AChE(acetylcholinesterase)inhibition as well as additional antioxidant capacities.展开更多
The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous poly...The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.展开更多
In this study,fucoidans were extracted from the sea cucumber Thelenota ananas(Ta-FUCs)by enzymatic degradation.Four products with molecular weights of 1380.3,524.0,182.4,and 110.3 kDa were obtained,and the Ta-FUC show...In this study,fucoidans were extracted from the sea cucumber Thelenota ananas(Ta-FUCs)by enzymatic degradation.Four products with molecular weights of 1380.3,524.0,182.4,and 110.3 kDa were obtained,and the Ta-FUC showing optimal anti-adipogenic activities was determined.Results of MTT and Oil red O staining analyses showed that the Ta-FUCs inhibited the proliferation and differentiation of 3T3-L1 adipocytes.Futhermore,Ta-FUCs significantly downregulated the key transcriptional factors,such as SREBP-1c,PPARγ,and C/EBPαof adipocytes.The Ta-FUCs also activated Wnt/β-catenin pathway-related genes,such asβ-catenin,LRP5,and FrZ.The Ta-FUCs suppressed lipid accumulation in 3T3-L1 adipocytes possibly by decreasing the expression of genes ACC,FAS,ME,GPAT,DGAT,and PILN,which are important in the synthesis of fatty acids and triglycerides;and by increasing the expression of genes PPARα,CPT-1α,and ACOX,which are crucial in fatty acidβ-oxidation.The anti-adipogenic activities initially increased and then declined with decreasing molecular weight.Among the Ta-FUCs,the 182.4 kDa Ta-FUC exhibited optimal bioactivities.This study reports for the first time that Ta-FUCs can prevent obesity by regulating the differentiation and lipid accumulation of adipocytes.展开更多
Low molecular weight (LMW) fucoidan, obtained by free radical depolymerization of high molecular polysaccharide extract of brown algae Hizikia fusiformis, was complexed with HPLC purified bee venom melittin. Water sol...Low molecular weight (LMW) fucoidan, obtained by free radical depolymerization of high molecular polysaccharide extract of brown algae Hizikia fusiformis, was complexed with HPLC purified bee venom melittin. Water soluble form of the LMW fucoidan – melittin complex shows increased anti-inflammatory activity, inhibiting the production of nitric oxide in murine macrophage cell line Raw 264.7. The LMW fucoidan:melitin complex obtained in this study showed good biological activities, resulting in 2-fold reduction of the melittin toxicity. The fucoidan: melittin macromolecular complex obtained should be useful in future therapeutic applications.展开更多
基金supported by the Special Fund for Clinical Scientific Research of Shandong Medical Association(No.YXH2020ZX058).
文摘This study was carried out explore the mechanism underlying the inhibition of platelet activation by kelp fucoidans in deep venous thrombosis(DVT)mouse.In the control and sham mice,the walls of deep vein were regular and smooth with intact intima,myometrium and adventitia.The blood vessel was wrapped with the tissue and there was no thrombosis in the lumen.In the DVT model,the wall was uneven with thicken intima,myometrium and adventitia.After treated with fucoidans LF1 and LF2,the thrombus was dissolved and the blood vessel was recanalized.Compared with the control group,the ROS content,ET-1 and VWF content and the expression of PKC-βand NF-κB in the model were significantly higher(P<0.05);these levels were significantly reduced following treatments with LF2 and LF1.Compared with H_(2)O_(2)treated-HUVECs,combined LF1 and LF2 treatment resulted in significant decrease in the expression of PKC-β,NF-κB,VWF and TM protein(P<0.05).It is clear that LF1 and LF2 reduces DVT-induced ET-1,VWF and TM expressions and production of ROS,thus inhibiting the activation of PKC-β/NF-κB signal pathway and the activation of coagulation system and ultimately reducing the formation of venous thrombus.
基金The“Basic Science Research Program”extended its support via the National Research Foundation of Korea (NRF),which is sponsored through the Ministry of Education (2018R1C1B6004780)supported by Main Research Program (E0211200-03)of the Korea Food Research Institute (KFRI)funded by the Ministry of Science and ICT。
文摘The prevalence of obesity has increased and is a health concern worldwide.Due to the concerns regarding synthetic anti-obesity treatments,nowadays natural products become a trend.Previous studies proved that there is a potential to use marine algae as anti-obesity agents.Therefore,in this study,the lipid inhibitory effect of crude polysaccharide of amyloglucosidase-assisted hydrolysate from Sargassum thunbergii(STAC)and its fucoidan fractions(STAFs)on 3T3-L1 cells and high-fat diet(HFD)-induced obese mice were investigated.According to the results,the STAF3,showed the highest xylose content and exhibited significant inhibitory effects on lipid accumulation by downregulating adipogenic and lipogenic proteins in 3T3-L1 cells.Furthermore,oral supplementation with STAC significantly declined gain in body weight and fat weight,and serum lipid contents in an HFD-induced obesity mouse model.Structural and chemical characterizations demonstrated that puritied STAF3 has consistent surface morphology and small particle size,with similar structural characteristics as commercial fucoidan.Together,these results indicate that STAC and purified STAF3 from Sargassum thunbergia is a potent source to develop as ananti-obesity agents or functional food products to counter obesity.
基金supported by the Priority Research Centers Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(Grant 2017R1A6A03015562 and RS-2023-00237386).
文摘Fucoidan,a sulfate polysaccharide obtained from brown seaweed,has various bioactive properties,including anti-inflammatory,anti-cancer,anti-viral,anti-oxidant,anti-coagulant,anti-thrombotic,anti-angiogenic,and anti-Helicobacter pylori properties.However,the effects of low-molecular-weight fucoidan(LMW-F)on melanoma cell lines and three dimensional(3D)cell culture models are not well understood.This study aimed to investigate the effects of LMW-F on A375 human melanoma cells and cryopreserved biospecimens derived from patients with advanced melanoma.Ultrasonic wave was used to fragment fucoidan derived from Fucus vesiculosus into smaller LMW-F.MTT and live/dead assays showed that LMW-F inhibited cell proliferation in both A375 cells and patientderived melanoma explants in a 3D-printed collagen scaffold.The PTEN/AKT pathway was found to be involved in the anti-melanoma effects of fucoidan.Western blot analysis revealed that LMW-F reduced the phosphorylation of Bcl-2 at Thr 56,which was associated with the prevention of anti-apoptotic activity of cancer cells.Our findings suggested that LMW-F could enhance anti-melanoma chemotherapy and improve the outcomes of patients with melanoma resistance.
基金Supported by the National Natural Science Foundation of China (Nos.42176137,81872906)the Nantong Science and Technology Project (No.MS12021037)+2 种基金the STS Program of Chinese Academy of Sciences (No.KFJ-STS-QYZD-195)the K.C.Wong Education FoundationCAS。
文摘The brown seaweed,Sacchairna japonica,has been used in traditional Chinese medicine for over one thousand years.Oral administration of fucoidan or low molecular weight fucoidan(LMWF)from S.japonica could ameliorate kidney dysfunction in chronic kidney diseases and inhibit diabetic vascular complications.In many studies,LMWF was found to be more potent than fucoidan with high molecular weight.However,the pharmacokinetics of LMWF still remains unclear.The purpose of the research is to compare the pharmacokinetics of fucoidan with high molecular weight(136 kDa)with that low molecular weight(9.5 kDa)after oral administration to ICR mice.Since fucose is the main and representative monosaccharide of fucoidans,we evaluate the pharmacokinetics of fucoidan and LMWF by determining the fucose concentration in mice serum.Both fucoidan and LMWF were absorbed following oral administration.Fucoidan and LMWF were provided to mice by oral administration with 60 mg/kg and the maximum Concentration(C_(max))was found at 2.5 h(0.66±0.32 mg/L)for Fucoidan and 1.5 h(1.01±0.56 mg/L)for LMWF,respectively.It seems that LMWF had a higher area under the curve(AUC_(0–t))and was absorbed more quickly than fucoidan.The estimated bioavailability of LMWF was28.3%in the mice treated with a single dose of 30 mg/kg.In addition,LMWF was found widely spreaded into different tissues following oral administration and the highest concentration was found in kidney at 19.93±7.02μg/g.In this study,we first studied the pharmacokinetics of LMWF,in order to help to understand the function of LMWF.And our results shed light on the potential of development of drugs based on LMWF.
基金Youth Research Project of Shanghai Health and Family Planning Commission (No.20174Y0201)。
文摘Objective:To study the preventive effect of fucoidan on non-alcoholic fatty liver disease induced by high fat diet.Methods:The experimental mice were randomly divided into three groups:control group,high-fat diet group and fucoidan intervention group.The control group was fed a standard diet,and the other two groups were fed a high-fat diet.The control group and the high-fat diet group were given normal saline intragastric administration every day,and the intervention group was given intragastric administration of fucoidan polysaccharide solution at a dose of 100 mg∙kg^(-1)∙d^(-1) once a day for continuous intervention for 12 weeks.After the last intragastric administration for 12 h,the body weight and liver weight of each group of mice were measured,and the liver index was calculated.The contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC)and triglyceride(TG)in liver tissues of mice in each group were detected by biochemical kit.Hematoxylin-eosin staining(HE)was used to compare the pathological morphological changes of liver tissue in each group.The contents of inflammatory factor interleukin-6(IL-6),tumor necrosis factor(TNF-α)and oxidative stress index malondialdehyde(MDA),and the activities of glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)in liver tissues of mice in each group were determined.Results:Compared with the control group,the body weight and liver index of mice receiving high fat diet increased significantly(P<0.01).In addition,the contents of TG,TC,AST and ALT in liver tissue of high-fat diet group were significantly increased compared with that of control group(P<0.01).The liver tissue of mice in the high-fat diet group also showed significant pathological changes,accompanied by increased expression of inflammatory factors and a significant increase in oxidative stress response.However,compared with the mice in the high-fat diet group,the above indexes were significantly improved in the liver tissue of the mice treated with fucoidan(P<0.01).Conclusion:Fucoidan can inhibit liver lipid deposition,liver inflammation and oxidative stress induced by high fat diet.
文摘AIM:To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells.METHODS:In Caco-2 cell monolayer models,the disruption of barrier function by oxidative stress is mediated by H2O2.The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance(TER)and permeability was estimated by measuring the paracellular transport of FITC-labeled4-kDa dextran(FD4).The protective effects of fucoidan on epithelial barrier functions on polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux.The expression of tight junction(TJ)proteins was assessed using reverse-transcription polymerase chain reaction(RT-PCR)and immunofluorescence staining.RESULTS:Without H2O2treatment,fucoidan significantly increased the TER compared to control(P<0.05),indicating a direct enhancement of intestinal epithelial barrier function.Next,H2O2disrupted the epithelial barrier function in a time-dependent manner.Fucoidan prevented the H2O2-induced destruction in a dosedependent manner.Fucoidan significantly decreased H2O2-induced FD4 flux(P<0.01),indicating the prevention of disruption in paracellular permeability.RTPCR showed that Caco-2 cells endogenously expressed claudin-1 and-2,and occludin and that H2O2reduced the mRNA expression of these TJ proteins.Treatment with fucoidan attenuated the reduction in the expressions of claudin-1 and claudin-2 but not occludin.Immunofluorescence staining revealed that the expression of claudin-1 was intact and high on the cell surface.H2O2disrupted the integrity of claudin-1.Treatment with fucoidan dramatically attenuated the expression of claudin-1.CONCLUSION:Fucoidan enhanced intestinal epithelial barrier function by upregulating the expression of claudin-1.Thus,fucoidan may be an appropriate therapy for the treatment of inflammatory bowel diseases.
基金the financial support from the National Natural Science Foundation of China(No.30800858)
文摘Fucoidan, a polysaccharide containing abundant fucose and sulfate ester group, was prepared from Laminaria japonica. In order to obtain fucoidan-degrading enzyme, bacteria capable of degrading fucoidan were screened from kelp. A bacterial strain named RC2-3 was obtained, which degraded fucoidan by the maximum extent of 54% ± 1.3%, the highest among all bacterial isolates. High-performance size exclusion chromatography(HPSEC) showed that the molecular weight of fucoidan was gradually reduced by RC2-3 with culturing time, suggesting the production of fucoidan-degrading enzyme by RC2-3. Phylogenetic analysis of partial 16S ribosomal RNA gene(16S rDNA) sequence showed that RC2-3 belonged to the family Flavobacteriaceae. However, it showed different physiological and biochemical characteristics from the known Flavobacteriaceae members producing fucoidan-degrading enzyme, thus RC2-3 was proposed to be a new member of this family.
基金supported by the Ministry of Oceans and Fisheries,Korea(the project title:Development of marine material based near infrared fluorophore complex and diagnostic imaging instruments)by a Grant(1910070)from the National Cancer Center
文摘In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy(PDT) to induce the com-plete death of cancer cells. A CFN-gel has nanomolar a nity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention e ect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar a nity for the vascular endothelial growth factor, it also provides a significant anti-tumor e ect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high e cacy and specificity.
文摘In Japan, S-1 plus cisplatin has become a standard regimen for the treatment of unresectable advanced gastric cancer;however, many patients are unable to continue effective chemotherapy because of the regimen’s severe side effects. Thus, control of drug toxicity is key to prolonging patient survival. Fucoidan is a major sulfated polysaccharide found in brown seaweeds and has a wide range of biological activities. In the present study, we analyzed the effect of fucoidan on suppressing the toxicity of chemotherapy drugs. Twenty-four patients with unresectable advanced gastric cancer underwent treatment with S-1 plus cisplatin and were randomly allocated into a fucoidan treatment group (n = 12) or a control group without fucoidan treatment (n = 12). The study results demonstrated that fucoidan controlled the occurrence of fatigue during chemotherapy and patients could continue chemotherapy for longer time periods by maintaining the patients’ favorable nourishment status. As a result, the survival of patients with fucoidan treatment was longer than that of patients without fucoidan. Thus, fucoidan should be included as a key food supplement for patients with gastrointestinal carcinomas who are suffering from the adverse side effects of chemotherapy.
文摘[Objectives] The research aimed to optimize extraction process of fucoidan from Sargassum fusiforme( FSF) and study its moisturizing performance. [Methods]Extracting condition of FSF by cellulase hydrolysis-ultrasonic assisted extraction method was optimized. The influences of solvent p H,enzyme dosage,extraction temperature,cellulose hydrolysis time,ultrasonication time,and the ratio of material to liquid on FSF were investigated by single factor and orthogonal experiments. [Results] The optimum extraction conditions were as followings:p H,4. 5; enzyme dosage,1%; extraction temperature,40℃; cellulose hydrolysis time,2 h; ultrasonic time,15 min; and the ratio of material to liquid,1∶ 10( g∶ m L). Under the optimal condition,the extraction yield of FSF was 8. 50%,RSD = 2. 74%. The short-time hygroscopicity( within 8 h) of crude extract of fucoidan from S. fusiforme( CEFSF) was better than glycerin,butanediol,and sodium alginate,and the moisture retention capacity of 1% CEFSF aqueous solution was better than 1% butanediol or 1% sodium alginate,and was equal to 5% glycerin under relative humidity of 43% and 81%. The determination results of skin moisture content and transepidermal water loss rate( TEWL)showed that: 5% CEFSF solution had good moisturizing effect. [Conclusions]The research could provide certain reference for deep development of S. fusiforme.
基金This work was supported by the grants from the National Natural Science Foundation of China(81830011,81670418,and 91739304 to Q.C.,81770417 to X.Z.,81870371 to J.B.,and 81670263 to X.L.)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(18KJA310003 to J.B.and 15KJA310001 to X.L.).
文摘Obesity is an escalating global pandemic posing a serious threat to human health.The intervention therapy using weight-reducing drugs,accompanied by lifestyle modification,is a strategy for the treatment of obesity.In the present study,we explored the role of fucoidan,a seaweed compound,on high-fat diet(HFD)-induced obesity in mice.We found that fucoidan treatment significantly reduced the body fat and caused redistribution of visceral and subcutaneous fat in HFD-fed mice.Meanwhile,fucoidan treatment inhibited adipocyte hypertrophy and inflammation in adipose tissue.Collectively,these results suggest that fucoidan may be a promising treatment for obesity and obesity-induced complications.
文摘Fucoidan is a sulfated polysaccharide that is primarily extracted from brown seaweeds which has been broadly studied in recent years due to its numerous biological properties, including anticoagulant, antithrombotic, antitumor, and antiviral activities. In this study, fucoidan was evaluated against clinic isolated methicillin-resistant Staphylococcus aureus (MRSA) 1 - 20, either alone or with antibiotics, via broth dilution method and checkerboard and time kill assay. Minimum inhibitory concentrations (MICs)/Minimum bactericidal concentrations (MBCs) values for the fucoidan against all the tested bacteria ranged between 64 - 512/256 - 2048 microg/mL, for ampicillin 32 - 1024/64 - 1024 microg/mL and for oxacillin 8 - 64/16 - 256 microg/mL respectively. Furthermore, the MIC and MBC were reduced to one half-eighth as a result of the combination of the fucoidan with antibiotics. 2 - 6 hours of treatment with 1/2 MIC of fucoidan with 1/2 MIC of antibiotics resulted from an increase of the rate of killing in units of CFU/mL to a greater degree than was observed with alone. These results suggest that fucoidan could be employed as a natural antibacterial agent against multi-drug bacteria.
基金The project supported by National Natural Science Foundation of China(81370339)Promotion Project of Beijing Education Committee(TJSHJ201510025005)
文摘OBJECTIVE To investigate the protective effect against diabetes cardiovascular complications of low molecular weight fucoidan(LMWF)from L.japonica in Qindao, China. METHODS LMWF(50,100 and 200mg·kg-1·d-1)or probucol(100mg·kg-1·d-1)were given orally to Goto-Kakizaki type 2 diabetic rats for 12 weeks.Basal blood pressure,acetylcholine-or flow-mediated relaxation of mesenteric and paw arteries,endothelium-dependent dilation of aorta,eNOS phosphorylation and NO production were measured using laser Doppler flowmetry,force myograph,HE staining,Western blot and an NO assay,respectively.The establishment of diabetic cardiomyopathy(DCM)model and were evaluated by echocardiography and isolated heart perfusion.Ventricle staining with HE or Sirius red was performed to investigate the structural changes in myocardium.Oxidative stress and apoptosis were evaluated by enzyme activities,protein expressions and cell stainings in both myocardial tissues and cultured cardiomyocytes.RESULTS In aorta,LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta,as well as mesenteric and paw arteries in diabetic rats.In addition,the reduction in endothelial nitric oxide synthase(eNOS)phosphorylation at Ser1177,eNOS expression and NO production due to diabetes were partially reversed by LMWF treatment.However,probucol,a lipid-modifying drug with antioxidant properties,displayed only mild effects.Moreover,LMWF induced,in a dose-dependent manner,endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta,and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells.On DCM,LMWF has a beneficial effect by enhancing myocardial contractility and mitigating cardiac fibrosis as well as the production of reactive oxygen species(ROS)and myocyte apoptosis in diabetic hearts.CONCLUSION These data demonstrate for the first time that fucoidan protects vasoendothelial and cardiac function against diabetic injury in type 2diabetes rats via,at least in part,preservation of eNOS function,amelioration of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis.Fucoidan is therefore a potential candidate drug for protection of endothelium and heart in diabetic cardiovascular complications.
基金The Iran National Science Foundation under contract No. 96015033
文摘Marine macroalgal sulfated fucose-containing polysaccharides,like fucoidan,have drawn significant attention due to their biotechnological potentials,such as anti-cancer,antioxidant,and anti-cholinesterase activities.The fucoidan derived from brown macroalgae Sargassum angustifolium species(FSA)was investigated for its cytotoxic effects and alterations in cell proliferation,and cell cycle-related gene expression in the present study occurred on NB4 cell line.The results showed that FSA would induce p53,p21,pro-apoptotic genes and increase expression of the p15 gene as a cell arrest marker.Also,FSA inhibited the anti-apoptotic effect of the Bcl-2 gene and decreased dnmt-1 gene expression.FSA significantly exhibited potent 2,2-diphenyl-1-picrylhydrazyl(DPPH)radical scavenging activity(p<0.05)with an IC_(50) value of 0.157 mg/mL and showed moderate anti-acetylcholinesterase activity with an IC_(50) value of 1.20μg/mL.These results indicated the potential of FSA for the development of therapeutic or preventive agents of cancer and Alzheimer’s disease mainly through cytotoxic effect and AChE(acetylcholinesterase)inhibition as well as additional antioxidant capacities.
基金supported by the National Key Research and Development projects intergovernmental cooperation in science and technology of China(2018YFE0126900)National Natural Science Foundation of China(82072025 and82072026)+2 种基金Zhejiang Provincial Natural Science Foundation(LQ21H180003)Key R&D Program of Lishui City(2021ZDYF12)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(2022RC088)。
文摘The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.
基金This study was supported by the National Key Research and Development Program of China(No.2018YFC0311203)the Key Research and Development Plan in Shandong Province(No.2016YYSP017).
文摘In this study,fucoidans were extracted from the sea cucumber Thelenota ananas(Ta-FUCs)by enzymatic degradation.Four products with molecular weights of 1380.3,524.0,182.4,and 110.3 kDa were obtained,and the Ta-FUC showing optimal anti-adipogenic activities was determined.Results of MTT and Oil red O staining analyses showed that the Ta-FUCs inhibited the proliferation and differentiation of 3T3-L1 adipocytes.Futhermore,Ta-FUCs significantly downregulated the key transcriptional factors,such as SREBP-1c,PPARγ,and C/EBPαof adipocytes.The Ta-FUCs also activated Wnt/β-catenin pathway-related genes,such asβ-catenin,LRP5,and FrZ.The Ta-FUCs suppressed lipid accumulation in 3T3-L1 adipocytes possibly by decreasing the expression of genes ACC,FAS,ME,GPAT,DGAT,and PILN,which are important in the synthesis of fatty acids and triglycerides;and by increasing the expression of genes PPARα,CPT-1α,and ACOX,which are crucial in fatty acidβ-oxidation.The anti-adipogenic activities initially increased and then declined with decreasing molecular weight.Among the Ta-FUCs,the 182.4 kDa Ta-FUC exhibited optimal bioactivities.This study reports for the first time that Ta-FUCs can prevent obesity by regulating the differentiation and lipid accumulation of adipocytes.
文摘Low molecular weight (LMW) fucoidan, obtained by free radical depolymerization of high molecular polysaccharide extract of brown algae Hizikia fusiformis, was complexed with HPLC purified bee venom melittin. Water soluble form of the LMW fucoidan – melittin complex shows increased anti-inflammatory activity, inhibiting the production of nitric oxide in murine macrophage cell line Raw 264.7. The LMW fucoidan:melitin complex obtained in this study showed good biological activities, resulting in 2-fold reduction of the melittin toxicity. The fucoidan: melittin macromolecular complex obtained should be useful in future therapeutic applications.
