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 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
目的探讨低分子量褐藻糖胶(LMWF)对小鼠单核细胞RAW264.7诱导成熟破骨细胞凋亡的影响。方法通过100ng/m L RANKL诱导RAW264.7细胞株分化为破骨细胞,经TRAP特异性染色和骨吸收陷窝对诱导后的细胞进行鉴定。鉴定成功后,用100 ng/m L RANK...目的探讨低分子量褐藻糖胶(LMWF)对小鼠单核细胞RAW264.7诱导成熟破骨细胞凋亡的影响。方法通过100ng/m L RANKL诱导RAW264.7细胞株分化为破骨细胞,经TRAP特异性染色和骨吸收陷窝对诱导后的细胞进行鉴定。鉴定成功后,用100 ng/m L RANKL诱导RAW264.7细胞株5 d后,使用含有LMWF的培养基继续培养3 d,通过对TRAP阳性细胞计数和分析骨吸收面积来观察低分子量褐藻糖胶对破骨细胞的抑制和骨吸收功能情况;采用流式细胞术检测LMWF对破骨细胞凋亡的影响,capsase-3活性测试试剂盒检测LMWF对capsase-3活性进行测定;RT-PCR检测LMWF对成熟破骨细胞BAX与BCL-2基因表达的影响。结果单纯采用100 ng/m L的RANKL可成功诱导成熟的、有功能的破骨细胞。LMWF可以明显抑制RANKL诱导成熟破骨细胞的形成以及成熟破骨细胞的骨吸收功能;流式细胞术显示LMWF可增加成熟破骨细胞的早期凋亡率;并且能升高capsase-3的活性;PCR显示LMWF可明显下调破骨细胞凋亡相关的BCL-2和上调BAX基因mRNA表达,降低BCL-2/BAX的比值。结论低分子量褐藻糖胶可抑制破骨细胞的活性与骨吸收能力,促进破骨细胞凋亡,其主要机制是通过下调BCL-2和上调BAX mRNA基因表达实现的。展开更多
采用超声波辅助过氧化氢的方法降解岩藻聚糖,采用膜分离制备分子量>50 ku和<50 ku 2个组分的低分子量岩藻聚糖组分,并以未降解的岩藻聚糖为对照测定其抗菌活性。通过多糖降解率、硫酸基团保留率和抗菌生物学活性的比较研究证明,...采用超声波辅助过氧化氢的方法降解岩藻聚糖,采用膜分离制备分子量>50 ku和<50 ku 2个组分的低分子量岩藻聚糖组分,并以未降解的岩藻聚糖为对照测定其抗菌活性。通过多糖降解率、硫酸基团保留率和抗菌生物学活性的比较研究证明,超声波辅助降解2 h时的降解效果较好,此时的水解率为30.73%,硫酸基团保留率在24.71%,抑菌圈直径为25 mm。此条件下所制备的低分子量岩藻聚糖具有较好的理化性质及抗菌生物学活性。展开更多
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.
