Spray-dried fucoidan microparticles for pulmonary delivery of antitubercular drugs

Pulmonary tuberculosis accounts for 80% of cases and the delivery of antitubercular drugs into the lungs allows targeting the infected organ and, possibly, reducing systemic drug toxicity. This work aimed at using fucoidan as matrix of inhalable microparticles that associate two first-line antitubercular drugs, for an application in pulmonary tuberculosis therapy. Fucoidan is composed of fucose and sulphated sugar residues, moieties described as being recognised by surface receptors of alveolar macrophages, which host mycobacteria. Inhalable fucoidan microparticles loaded with antitubercular drugs were successfully produced with high association efficiencies of either isoniazid (95%) or rifabutin (81%). The microparticles evidenced no cytotoxicity on lung epithelial cells (A549). However, rifabutin-loaded microparticles showed a certain degree of toxicity on macrophage-like cells (THP-1) at the highest tested concentration (1?mg/mL). Furthermore, microparticles showed favourable aerodynamic properties for deep lung delivery (MMAD 2.0–3.8?µm) and, thus, show potential for an application as inhalable tuberculosis therapy.     

Exploiting biological activities of brown seaweed Ecklonia cava for potential industrial applications: a review

Seaweeds are rich in vitamins, minerals, dietary fibres, proteins, polysaccharides and various functional polyphenols. Many researchers have focused on brown algae as a potential source of bioactive materials in the past few decades. Ecklonia cava is a brown seaweed that is abundant in the subtidal regions of Jeju Island in the Republic of Korea. This seaweed attracted extensive interest due to its multiple biological activities. E. cava has been identified as a potential producer of wide spectrum of natural substances such as carotenoids, fucoidans and phlorotannins showing different biological activities in vital industrial applications including pharmaceutical, nutraceutical, cosmeceutical and functional food. This review focuses on biological activities of the brown seaweed E. cava based on latest research results, including antioxidant, anticoagulative, antimicrobial, antihuman immunodeficiency virus, anti-inflammatory, immunomodulatory, antimutagenic, antitumour and anticancer effects. The facts summarized here may provide novel insights into the functions of E. cava and its derivatives and potentially enable their use as functional ingredients in potential industrial applications.     

海参岩藻聚糖硫酸酯对巨噬细胞的调节作用及信号通路研究

目的研究海参岩藻聚糖硫酸酯(SC-FUC)对巨噬细胞的调节作用及相关信号通路,探究其调节机体免疫的作用机制。方法噻唑蓝(MTT)比色法检测巨噬细胞的增殖情况;中性红法检测吞噬活性;Griess试剂法测定培养上清液中NO含量;RT-PCR检测巨噬细胞下游细胞因子IL-6、IL-10、Toll样受体和相关信号分子My D88、TRIF、NF-κB的mRNA表达量。结果 SC-FUC对巨噬细胞增殖、吞噬能力和NO分泌均有促进作用,在作用前期(6h和12h)效果更为明显。SC-FUC能上调细胞因子IL-6和IL-10的mRNA表达量,上调TLR4、TLR5、TLR9的表达量,促进信号分子My D88、TRIF和NF-κB的mRNA表达量。结论 SC-FUC能够激活巨噬细胞,促进其分泌NO、IL-6、IL-10等细胞因子,从而发挥免疫调节作用。SC-FUC激活巨噬细胞的信号通路与细胞表面TLR4、TLR5、TLR9及NF-κB通路相关。     

岩藻聚糖硫酸酯FV对大鼠的抗血栓作用研究

目的探讨岩藻聚糖硫酸酯FV对大鼠的抗血栓作用。方法将60只Wistar大鼠随机分为对照组、岩藻聚糖硫酸酯FV 20、10、5、2.5 mg/kg组和低分子肝素钙注射液(LMWHC)213 IU/kg组,每组各10只。分别在下腔静脉血栓模型、体外血栓模型和动静脉旁路血栓模型中研究FV的抗血栓作用,比较血栓干湿质量并计算血栓抑制率。结果 FV 20、10、5、2.5mg/kg能够显著降低大鼠下腔静脉血栓、体外形成的血栓、动静脉旁路中血栓的干湿质量,对血栓湿质量的抑制率最高可达97.4%、94.3%、51.2%,对血栓干质量的抑制率最高可达91.8%、96.6%、64.0%,有明显的抑制血栓形成作用。结论 FV能够抑制血栓形成,量效关系好,具有开发为抗血栓药的良好前景。     

褐藻糖胶促进小鼠巨噬细胞免疫活性及机制初探

目的 探讨褐藻糖胶(Fucoidan)对小鼠巨噬细胞RAW264.7免疫活性的影响及初步探讨作用机制。方法 采用体外细胞培养方法,比色分析检测不同浓度Fucoidan(0、100、200、300、400、500 μg/mL)作用下RAW264.7吞噬中性红的能力,噻唑蓝(MTT)法检测不同浓度Fucoidan(0、50、250、500 μg/mL)作用下RAW264.7增殖,Western Blotting检测Fucoidan诱导的RAW264.7的MAPK/ERK1/2的磷酸化。结果 Fucoidan剂量依赖性地促进RAW264.7吞噬功能和增殖功能。200 μg/mL Fucoidan作用10min即使ERK1/2发生磷酸化,30min时ERK1/2磷酸化达到最大值。结论 Fucoidan可提高小鼠巨噬细胞的吞噬活性和增殖能力,其机制可能与Fucoidan直接激活RAW264.7的MAPK/ERK1/2信号转导通路有关。     

HILIC-ELSD法测定岩藻聚糖硫酸酯中岩藻糖

目的 建立一种简便、高效、准确的测定岩藻聚糖硫酸酯中岩藻糖的方法。方法 采用超声处理(300 W 100%,20 ℃,20 min);三氟乙酸(4 mol/mL)水解(110 ℃、2 h);亲水作用色谱-蒸发光检测(HILIC-ELSD)法检测,Waters XBridge^TM Amide(150 mm×4.6 mm,3.5 μm)色谱柱,流动相为乙腈-水-氨水(90:10:0.2),体积流量1 mL/min,柱温60 ℃。结果 岩藻糖的线性范围为0.100 4~1.004 mg/mL(r=0.999 4),平均加样回收率95.22%(n=6,RSD=1.16%)。结论 该方法简便、快速、准确,为岩藻聚糖硫酸酯的定量分析和质量评价研究提供了依据。     

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...     

褐藻来源硫酸岩藻聚糖的化学组成与结构的研究进展

褐藻硫酸岩藻聚糖是来源于褐藻的结构复杂的1类海洋硫酸多糖,主要由岩藻糖、半乳糖、甘露糖和葡萄糖醛酸组成,并含有少量的木糖、葡萄糖、鼠李糖、阿拉伯糖和氨基葡萄糖.研究表明,褐藻硫酸岩藻聚糖的主链是由α(1→3)或α(1→3)、α(1→4)交替连接的硫酸化L-岩藻糖构成,还嵌有半乳糖、葡萄糖醛酸等,而厚叶解曼藻和羊栖菜等褐...     

The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P- and L-selectin function in vivo

BACKGROUND: Adhesion molecules of the selectin family (mainly P- and L-selectin) have been suggested to mediate interactions between platelets, leukocytes and endothelial cells in thrombus formation. The polysaccharide fucoidan has anticoagulative properties, but is also able to bind and block the function of the selectins. Here, we investigated in vivo (i) if fucoidan can prevent microvascular thrombus formation, and (ii) whether this is potentially mediated by the inhibition of P-and/or L-selectin. MATERIALS AND METHODS: For this purpose, we used intravital microscopy in the mouse cremaster microcirculation in which thrombosis was induced photochemically by light exposure to individual arterioles and venules after intravenous (i.v.) injection of FITC-dextran. RESULTS: We found that intravenous administration of fucoidan significantly prolonged the time required for complete occlusion in arterioles and venules by almost seven- and nine-fold, respectively. In contrast, treatment with monoclonal antibodies against P- and L-selectin had no effect on the development of microvascular thrombosis. Fucoidan and also the anti-P-selectin antibody completely inhibited baseline venular leukocyte rolling in the cremaster muscle, indicating that these treatment regimes abolished P-selectin function. Importantly, fucoidan and the anti-P-selectin antibody had no effect on systemic platelet and leukocyte counts. On the other hand, we found that fucoidan treatment significantly altered coagulation parameters, including prothrombin time (Quick percentage), activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), which may explain the potent in vivo anticoagulative effect of fucoidan observed here. CONCLUSIONS: Taken together, our novel findings suggest that fucoidan effectively prevents microvascular thrombus formation induced by endothelial damage in arterioles and venules in vivo. This protective effect of fucoidan is not attributable to inhibition of P- and L-selectin function but may instead be related to the anticoagulative capacity of fucoidan.