小有刺参硫酸软骨素和岩藻聚糖硫酸酯抗血小板聚集活性的比较

目的 从小有刺参中制备纯化硫酸软骨素和岩藻聚糖硫酸酯及其低分子量组分,并比较不同结构硫酸多糖的抗血小板聚集活性,揭示海参硫酸多糖抗血小板聚集活性的构效关系。方法 利用离子交换色谱和自由基降解技术,从小有刺参中制备硫酸软骨素和岩藻聚糖硫酸酯及各自的低分子量组分。采用体外凝血酶诱导血小板聚集模型,比较不同结构的硫酸软骨素和岩藻聚糖硫酸酯对血小板聚集率的影响。结果 4～60 μg/mL硫酸软骨素和低分子量硫酸软骨素具有显著的抑制血小板聚集的活性,在浓度为20 μg/mL时对血小板聚集的抑制率高达94.6%和95.3%,且分子量的降低对其活性无影响。比较不同来源的岩藻聚糖硫酸酯的活性发现,在4～60 μg/mL浓度范围内,海参与海带来源的岩藻聚糖硫酸酯都显著抑制血小板聚集,且活性没有显著差异,但经过自由基降解后,海参和海带来源的岩藻聚糖硫酸酯的抗血小板聚集活性都显著降低。结论 海参硫酸软骨素的抗血小板聚集活性显著高于岩藻聚糖硫酸酯,海参硫酸多糖可以应用于新型抗血小板聚集药物的研究开发。     

海带低分子量岩藻聚糖硫酸酯的制备和抗血小板聚集活性研究

目的：研究低分子量海带岩藻聚糖硫酸酯的制备和纯化技术,筛选抗血小板聚集活性的低分子量海带岩藻聚糖硫酸酯。方法：以海带硫酸多糖为原料,采用自由基降解和强阴离子交换色谱技术,制备纯化出高硫酸根和高岩藻糖的低分子量岩藻聚糖硫酸酯;采用体外凝血酶诱导血小板聚集模型,筛选出抗血小板聚集活性的低分子量岩藻聚糖硫酸酯。结果：强阴离子交换色谱能够有效地将复杂的低分子量海带岩藻聚糖硫酸酯分离纯化,得到4个纯度较高的高硫酸根、高岩藻糖的低分子量多糖,其岩藻糖含量超过85% ~ 95%,硫酸根含量35%以上,分子量在20 ku ~ 30 ku。体外抗血小板聚集试验结果证明,这4个高硫酸根高岩藻糖组分的抗血小板聚集活性最高,而低硫酸根组分含有较高的半乳糖、甘露糖和糖醛酸,其抗血小板活性非常低。结论：采用自由基氧化降解和强阴离子交换色谱法,可获得抗血小板活性高的高硫酸根高岩藻糖的低分子量岩藻聚糖硫酸酯。     

相对低分子质量岩藻聚糖硫酸酯治疗慢性乙酸胃溃疡的临床研究

目的：观察慢性乙酸胃溃疡在低分子质量的岩藻聚糖硫酸酯作用下的疗效。方法：用灌胃方法对患有乙酸胃溃疡的白鼠灌输分子质量较低的岩藻聚糖硫酸酯,设为试验组;单纯乙酸胃溃疡白鼠设为对照组。观察胃溃疡白鼠在岩藻聚糖硫酸酯作用下胃部溃疡的情况、受氧程度、一氧化氮产生情况以及对过氧化物酶活性的影响。结果：胃溃疡白鼠接受低分子质量岩藻聚糖硫酸酯灌输后,胃黏膜损伤得到一定修复,与对照组白鼠相比,溃疡面积有所减少,同时,在岩藻聚糖硫酸酯的作用下,胃部抗氧化酶得到了很好的保护,过氧化物酶得到了明显抑制。相比对照组白鼠,试验组白鼠胃中一氧化氮含量明显上升,过氧化物活性大幅度下降。结论：抗氧化物的活性影响了岩藻聚糖硫酸酯对辅助治疗的效果,同时,岩藻聚糖硫酸酯对白鼠慢性乙酸胃溃疡有辅助治疗的效果。乙酸慢性胃溃疡在一氧化氮的产生以及炎症细胞辅助下得到了很好的修复,溃疡也得到了愈合的效果。     

从棕色海藻中得到的抗病毒多糖硫酸酯

许多多糖硫酸酯如葡聚糖硫酸酯、肝素、戊聚糖多硫酸酯对HIV培养物都有较强的选择抑制活性。它们可抑制细胞匀浆中的HIV逆转录酶,故其抗病毒活性基本可以肯定是由于阻断了病毒吸附于细胞表面而导致的。作者从黄墨角藻Ascophyllum nodosum(即岩藻)中分出两个岩藻聚糖硫酸酯GXF和Asco。GXF为由葡萄糖醛酸、木糖和岩藻糖组成,分子量约30000,而Asco为一杂多糖混     

分子量对海参岩藻聚糖硫酸酯在体内吸收的影响

目的 利用高温高压降解法制备两种不同分子量的岩藻聚糖硫酸酯,探究口服不同分子量的海参岩藻聚糖硫酸酯的吸收特性。方法 采用分子排阻凝胶色谱法、离子高效液相色谱法,检测海参硫酸多糖高温高压降解前后分子量、硫酸根含量的变化,并利用PMP柱前衍生-高效液相色谱法测定岩藻聚糖硫酸酯的单糖组成,以及大鼠血清中单糖的变化。结果 口服低分子量海参岩藻聚糖硫酸酯后,大鼠血清中岩藻糖和半乳糖的吸收速度和最大浓度明显高于中分子量岩藻聚糖组,血清中甘露糖、氨基葡萄糖的含量也显著上升,血清中氨基半乳糖的含量略有上升。而口服中、低分子量岩藻聚糖硫酸酯都能够降低血清中葡萄糖的含量。结论 分子量低于10 kDa的低分子量岩藻聚糖具有很好的体内的吸收率,适合于开发口服岩藻聚糖功能产品。     

海带岩藻聚糖硫酸酯对栓塞性脑缺血损伤的保护及作用机制的研究D

目的 对不同分子量海带岩藻聚糖硫酸酯对大鼠栓塞性脑缺血损伤的保护活性及其作用机制进行研究比较。方法 以海带高分子量和低分子量岩藻聚糖硫酸酯为研究对象,采用电刺激造栓法建立大鼠动脉栓塞性脑缺血损伤模型,观察岩藻聚糖硫酸酯对神经行为学评分、脑梗死体积、大脑皮层形态学、血液中花生四烯酸代谢产物（TXB2和6-kelo-PGF1α）、磷脂代谢产物（PA和LPA）和纤溶系统（t-PA和u-PA）的影响。结果 静脉注射高分子量和低分子量岩藻聚糖硫酸酯对大鼠栓塞性脑缺血损伤具有很好的保护作用,显著降低神经行为学评分、脑梗死体积和脑皮层神经细胞的损伤,低分子量岩藻聚糖硫酸酯的保护活性是高分子量组分的1/10。岩藻聚糖硫酸酯预防栓塞性脑缺血损伤的作用机理为：抑制TXB2生成,提高6-kelo-PGF1α的水平,抑制LPA的释放,从而抑制血栓的进一步发展;促进t-PA和u-PA的生成从而激活纤溶系统。结论：岩藻聚糖硫酸酯在预防栓塞性脑缺血损伤方面具有很好的应用潜质。     

褐藻中岩藻聚糖硫酸酯抗凝血活性研究

目的对褐藻中岩藻聚糖硫酸酯的抗凝血活性进行研究。方法将20只新西兰白兔随机分为2组：岩藻聚糖硫酸酯组和空白对照组，分别测定其APTT、PT和TT。结果岩藻聚糖硫酸酯组和空白对照组APTT测定分别为62．7±11．3（s）、35．6±9．7（s），P〈0．05，差别有显著性意义；PT测定分别为19．5±4．8（s）、13．4±4．7（s），P〈0．05，差别有显著意义；TT测定分别为39．3±9．8（s）、21．5±7．3（s），P〈0．05，差别有显著性意义。结论褐藻中岩藻聚糖硫酸酯具有显著的抗凝血活性。     

不同性质海洋硫酸多糖的制备及其改善大鼠脂肪肝作用的比较研究

目的 探索了不同来源、不同分子量的海洋硫酸多糖对脂肪肝大鼠脂肪代谢的调节作用.方法 SD大鼠随机分为7组,正常对照组、脂肪肝模型对照组、0.1%低分子量海参岩藻聚糖硫酸酯组、0.1%海参岩藻聚糖硫酸酯组、0.2%海参岩藻聚糖硫酸酯组、0.2%海藻岩藻聚糖硫酸酯组、0.2%海参硫酸软骨素组,每组6只.饲料中添加1%乳清酸...     

岩藻聚糖硫酸酯F2靶向SGLT2的抗糖尿病肾病活性研究

目的 旨在从细胞水平上探讨岩藻聚糖硫酸酯F2对SGLT2的抑制作用及抗糖尿病肾病(DN)活性,并阐述其抗DN机制。方法 通过Q-Sepharose Fast Flow强阴离子交换层析法对墨角藻来源岩藻聚糖硫酸酯(FvF)进行分离纯化,并采用高效液相、离子色谱等方法测定其分子量、单糖组成、硫酸根含量等基本理化性质,利用流式细胞术,通过评价样品对SGLT2稳转细胞转运葡萄糖能力的影响,来分析样品对SGLT2的抑制活性,确定活性最优化合物。通过计算机模拟技术,探讨了岩藻寡糖与SGLT2的相互作用。采用大鼠肾系膜细胞(HBZY-1细胞),利用高糖诱导,建立HBZY-1细胞增殖模型,通过MTT法评价F2的抗DN活性,并利用Western Blot方法探究最优化合物对HBZY-1细胞模型中SphK1、NF-κB、p38、ERK1/2蛋白的影响。结果 纯化后获得了5个组分,SGLT2抑制剂筛选确定F2为最优组分,其具有分子量低、硫酸根含量高且单糖组成较为单一的特点,并且岩藻糖中硫酸根含量和聚合度影响其与SGLT2的相互作用,而2-硫酸岩藻八糖与SGLT2的亲和力最强。成功建立了HBZY-1细胞增殖模型,发现F2在较低浓度下即可发挥抗肾系膜增生作用,并且其活性随着浓度增加而增强,且F2是通过抑制SphK1、NF-κB、p38蛋白的表达,抑制ERK1/2蛋白的磷酸化来发挥抗DN活性。     

壳聚糖-岩藻聚糖硫酸酯纳米粒的制备及性质研究

目的：本文以低分子量岩藻聚糖硫酸酯为交联剂,研究了聚电解质凝聚法制备壳聚糖-岩藻聚糖硫酸酯纳米微粒(Chitosan-fucoidan nanoparticles, CS-Fuc NPs)的制备工艺,并对纳米粒的胃肠道和贮藏稳定性进行研究。方法：采用聚电解质凝聚法制备壳聚糖-岩藻聚糖硫酸酯纳米微粒,采用体外模拟胃液和模拟肠液消化体系,检测纳米粒的胃肠稳定性,常温贮藏实验测定纳米粒的短期贮藏稳定性。结果：壳聚糖-岩藻聚糖硫酸酯纳米微粒的最优制备条件是：壳聚糖(1mg/ml)与岩藻聚糖硫酸酯(1mg/ml)体积比为1.1/1,pH 4.5,温度30℃。所得纳米粒粒径为227.8 nm,Zeta电位为38.4 mV,PDI为0.231,岩藻聚糖硫酸酯复合率(Fuc%)为94.92%。所制备的纳米颗粒在10周内没有显著变化,在模拟胃环境中稳定性良好,在模拟肠道环境中解聚性良好。结论： 壳聚糖-岩藻聚糖硫酸酯纳米粒制备工艺简单,性能良好,有望成为新型的口服药物运送载体。     

褐藻糖胶药理活性研究进展

褐藻糖胶是一类来自于海洋褐藻和无脊椎动物的杂多糖,主要成分为硫酸化的岩藻糖及少量的半乳糖、甘露糖、木糖及糖醛酸等。现有研究表明,褐藻糖胶具有诸多药理活性,如抗氧化、抗肿瘤、抗凝血、免疫调节、抗菌抗病毒、降糖降血脂、神经保护等。本文对褐藻糖胶目前研究的主要药理活性进行了总结,以期为其进一步研究和开发提供参考。     

Fibrinolytic and anticoagulant activities of highly sulfated fucoidan.

A series of fucoidan [sulfated poly(L-fucopyranose)] derivatives were prepared by chemical sulfation and desulfation, and they were tested for their abilities to stimulate tissue plasminogen activator (t-PA)-catalyzed plasminogen activation, clot lysis, and the inhibition of fibrin polymer formation. The magnitude of their activities was dependent upon the degree of sulfation. A striking feature of the sulfated fucoidan was that, unlike heparin, it stimulated t-PA-induced plasma clot lysis by protecting plasmin activity from alpha 2-plasmin inhibitor and decreased the rate of fibrin polymer formation. The inhibition of hyaluronic acid-mediated enhancement of fibrin clot formation was also observed with the fucoidan derivative. We also showed that highly sulfated fucoidan prevents significantly endotoxin-induced hepatic vein thrombosis in the hyperlipemic rat model. The present results are the first to describe the fibrinolytic and anticoagulant activities of fucoidan, and thus may provide useful clues for the development of an ideal thrombolytic agent.     

岩藻多糖的药理作用研究进展

岩藻多糖是从褐藻细胞壁和细胞间质中分离得到的一类天然硫酸化杂多糖。岩藻多糖具有多样的生物活性，如抗炎、抗肿瘤、神经保护、抗凝、调节肠道菌群、调节血脂、抗病毒作用。对岩藻多糖的药理作用进行了总结，以期为进一步开发利用岩藻多糖提供参考。     

Fucoidan partly prevents CCl4-induced liver fibrosis

Fucoidan, a sulfated polysaccharide extracted from brown algae, has a wide range of biological activities, including anti-inflammatory, anti-viral, and anti-tumor activities. In the present study, we investigated the effects of fucoidan on CCl₄-induced liver fibrosis. Administration of fucoidan reduced CCl₄-induced acute and chronic liver failure. Hepatic fibrosis induced by CCl₄ was also attenuated by injection of fucoidan. Damage to hepatocytes and activation of hepatic stellate cells are key events in liver fibrosis, and, interestingly, treatment of hepatocytes with fucoidan prevented CCl₄-induced cell death and inhibited the proliferation hepatic stellate cells. These results indicate that fucoidan might be a promising anti-fibrotic agent possessing dual functions, namely, protection of hepatocytes and inhibition of hepatic stellate cell proliferation.     

Protective effect of fucoidan against acetaminophen-induced liver injury

Fucoidan, a sulfated polysaccharide extracted from various brown seaweeds, possesses a wide range of pharmacological properties. In this study, we investigated the protective effect of fucoidan on acetaminophen-induced acute liver injury in rats. Liver injury was induced by administration of acetaminophen (800 mg/kg, i.p.) and fucoidan was administered (100 mg kg, p.o.) 2 h before and after acetaminophen administration. After 24 h, co-treatment of fucoidan ameliorated liver damage and cell death induced by acetaminophen. Acetaminophen induced the overexpression of CYP2E1, one of the metabolizing enzymes of acetaminophen, but cotreatment with fucoidan suppressed its increased expression of CYP2E1. Fucoidan also reduced the hepatic apoptosis induced by acetaminophen exposure as shown in the protein expression of Bax, Bcl-2, and cleaved caspase-3. The anti-oxidative effect of fucoidan was observed from the increase of the production and expression of glutathione, superoxide dismutase, and glutathione peroxidase, both of which were decreased by acetaminophen. Also, fucoidan decreased the expression of inflammatory mediators, including tumor necrosis factoralpha, interleukin 1 beta, and inducible nitric oxide synthase. Taken together, the data demonstrate the hepato-protective effects of fucoidan against acetaminophen-induced liver injury via anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms.     

Fucoidan Enhances the Survival and Sustains the Number of Splenic Dendritic Cells in Mouse Endotoxemia

Fucoidan is a sulfated polysaccharide derived from brown algae that has been reported to perform multiple biological activities, including immunostimulation. In this study, we investigated whether fucoidan has beneficial effects on endotoxemia induced by LPS, a septic model in mice. The focus of this study was on survival rates and spleen function of the mice upon treatment. We found that fucoidan had prophylactic effects on the survival rate of mice with endotoxemia. Flow cytometric analysis using antibodies for subset-specific markers revealed that fucoidan profoundly reversed the depleted population of dendritic cells in mice with endotoxemia. According to Western blot analysis, the spleen cells of LPS/fucoidan-treated mice showed a higher expression of anti-apoptotic molecules compared to those of LPS-treated mice. Also, fucoidan-treated spleen cells were more responsive to mitogens. Taken together, these results demonstrate that fucoidan pre-treatment has beneficial effects on the survival rate and function of the spleen in mice with endotoxemia. This study may broaden the use of fucoidan in clinical fields, especially endotoxemia.     

Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities

Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has anticoagulant and antithrombotic activities. Unlike heparin, it shows an inhibitory action on the progression and metastasis of malignant tumors, although the precise mechanisms have not been elucidated. We have demonstrated previously that fucoidan can inhibit tube formation following migration of human umbilical vein endothelial cells (HUVEC) and that its chemical oversulfation enhances the inhibitory potency. In this study, we tested the hypothesis that fucoidan may suppress tumor growth by inhibiting tumor-induced angiogenesis. Both natural and oversulfated fucoidans (NF and OSF) significantly suppressed the mitogenic and chemotactic actions of vascular endothelial growth factor 165 (VEGF(165)) on HUVEC by preventing the binding of VEGF(165) to its cell surface receptor. The suppressive effect of OSF was more potent than that of NF, suggesting an important role for the numbers of sulfate groups in the fucoidan molecule. Consistent with its inhibitory actions on VEGF(165), OSF clearly suppressed the neovascularization induced by Sarcoma 180 cells that had been implanted in mice. The inhibitory action of fucoidan was also observed in the growth of Lewis lung carcinoma and B16 melanoma in mice. These results indicate that the antitumor action of fucoidan is due, at least in part, to its anti-angiogenic potency and that increasing the number of sulfate groups in the fucoidan molecule contributes to the effectiveness of its anti-angiogenic and antitumor activities.     

Inhibitory effect of fucoidan on the activities of crotaline snake venom myotoxic phospholipases A(2)

Myotoxic phospholipases A(2) account for most of the muscle necrosis that results from envenenomation by crotaline snakes. In this study, we investigated the protective effect of fucoidan, a natural sulfated polysaccharide obtained from the brown seaweed Fucus vesiculosus, against the cytotoxic and myotoxic activities of a group of phospholipase A(2) myotoxins from crotaline snake venoms: Bothrops asper myotoxins I, II, III, and IV, Cerrophidion godmani myotoxins I and II, Atropoides nummifer myotoxins I and II, and Bothriechis schlegelii myotoxin I. All of the toxins tested were efficiently inhibited by fucoidan, in both their cytotoxic and myotoxic effects. The basis for this inhibition appears to be the rapid formation of complexes between fucoidan and myotoxins, as evidenced by turbidimetric analysis. The possible binding site of fucoidan on the myotoxins was investigated using short synthetic peptides that represent the membrane-damaging region (residues 115-129) for three of these toxins. Fucoidan clearly inhibited the cytolytic activity of the peptides, indicating its ability to interact with the C-terminal myotoxic region of these phospholipases A(2). Fucoidan significantly inhibited muscle damage in mice, when administered locally, immediately after experimental envenomation with crude venom from B. asper. These results encourage further studies of sulfated fucans as compounds of potential use to improve the treatment of envenomations by crotaline snakes.     

Genotoxicity studies on fucoidan from Sporophyll of Undaria pinnatifida

The sulfated seaweed extract, fucoidan, has anticoagulant, antithrombotic, and antiviral activities. Despite extensive work on the biological activities of fucoidan, detailed studies on the genotoxicity of fucoidan from Sporophyll of Undaria pinnatifida sources have not been tested before. The objective of this study was to investigate the genotoxicity effects of fucoidan extracted from Sporophyll of U. pinnatifida using a test battery of three different methods. In a reverse mutation assay using four Salmonella typhimurium strains and Escherichia coli, fucoidan did not increase the number of revertant colonies in any tester strain regardless of metabolic activation by S9 mix, and did not cause chromosomal aberration in short tests with S9 mix or in the continuous (24 h) test. A bone marrow micronucleus test in ICR mice dosed by oral gavage at doses up to 2000 mg/kg bw/day showed no significant or dose-dependent increases in the frequency of micronucleated polychromatic erythrocytes (MNPCE), and the high dose suppressed the ratio of polychromatic erythrocytes (PCE) to total erythrocytes. We conclude that fucoidan presents no significant genotoxic concern under the anticipated conditions of use.