黄芩苷抗炎作用机制的研究进展

黄芩苷(baicalin)是由黄芩(Scutellaria baicalensis Georgi)根部分离而来的黄酮类物质,为黄芩的主要活性成分。黄芩苷药理作用广泛,具有良好的抗炎效果,其主要机制包括调节肠道菌群、抑制核因子κB(NF-κB)核转位、增加相关microRNA的表达、抑制自噬、调节Treg/Th17平衡等。现综述黄芩苷抗炎症作用机制的最新研究进展,为其深入研究及在临床上的应用提供依据。     

黄芩苷的生物学功能及作用机理

黄芩苷(baicalin)是一种具有生物活性的黄酮类化合物,其为多年生草本植物黄芩的主要有效成分。目前相关细胞实验与动物实验均表明,黄芩苷具有多种生物学功能,该文通过查阅近年来国内外的最新相关文献,着重从黄芩苷保肝、护脑、抗氧化、抗糖尿病、抗肿瘤以及与microRNA的作用等方面的功能及其作用机理进行综述,旨在为黄芩苷的进一步开发及临床应用提供新的参考依据。     

温度和相对湿度对黄芩苷吸湿性的影响和模型拟合研究

黄芩苷是从黄芩根部提取的黄酮类化合物,具有抗菌、利尿、抗炎、解痉和抗肿瘤作用,它含有羟基、羧基等极性基团,因此会吸附空气中水蒸气而具有吸湿性。本文研究温度和相对湿度对黄芩苷吸湿性的影响并对其吸湿数据进行模型拟合,结果表明低温和高湿度导致黄芩苷具有较高的平衡吸湿量和较大的吸湿速度;1st Opt软件统计分析得出吸湿动力学双指数模型、吸附等温线Peleg模型拟合效果较好。     

黄芩苷对肺癌细胞A549增殖和迁移的作用研究

肿瘤恶化的根本原因是肿瘤细胞的过度增殖和转移,黄芩苷作为一种黄酮类天然药物,对保护血管功能、抑菌、消炎等都具有良好的效果。本研究观察不同浓度黄芩苷对体外培养人肺癌A549细胞的增殖和迁移的作用,探讨黄芩对肿瘤细胞转移的调控作用,以期开发黄芩苷作为肿瘤抑制药物的重要潜能。将0μm/L、20μm/L、40μm/L、60μm/L、80μm/L和100μm/L的黄芩苷处理细胞6 h,采噻唑蓝(MTT)、Tranwell小室迁移、显微形态观察等细胞学方法检测不同浓度的黄芩苷对细胞增殖和迁移的影响。结果显示,与对照组相比,不同浓度的黄芩苷均能抑制肺癌细胞的增殖和迁移,且抑制作用呈剂量依赖效应,80μm/L和100μm/L的黄芩苷能显著抑制肺癌细胞的增殖效率(p0.01)。我们得出这样的结论,黄芩苷对肺癌细胞的增殖和迁移具有抑制作用,且抑制效果与药物使用剂量正相关,黄芩苷对于肿瘤治疗效果的研究具有重要意义,有望成为高效抑制肿瘤发生的候选药物。     

黄芩苷抗肺炎衣原体的研究

目的观察黄芩苷抗肺炎衣原体的作用及对血管内皮细胞的保护作用。方法在24孔板培养人脐静脉内皮细胞（ECV-304）,板底放置一载玻片,待长成单层后加入肺炎衣原体（CPN）为模型组,加入CPN和黄芩苷0.48、0.24g/L为实验组,加入0.078g/L阿奇霉素为西药组,不加任何刺激物为正常组,每组设3个复孔,培养4d后,各组细胞进行姬姆萨染色观察细胞病变和衣原体的包涵体产生情况。结果血管内皮细胞细CPN刺激后细胞浆中有大量的空泡,包涵体为紫色芝麻状小颗粒;黄芩苷高剂量作用后血管内皮细胞空泡消失,包涵体平均值下降,结论黄芩苷有抗肺炎衣原体和保护细胞作用。     

黄芩苷对嗜水气单胞菌生物膜形成的影响及体内外的抑菌作用

[目的] 探讨中药单体黄芩苷对嗜水气单胞菌在体内外生长及生物膜形成的影响。[方法] 体外实验中,利用牛津杯法检测抑菌圈直径,结晶紫法检测生物膜的形成,通过泳动实验检测黄芩苷对嗜水气单胞菌运动性的影响,紫外吸收法检测细胞膜完整性,用透射电镜技术观察黄芩苷对细菌形态的影响。体内实验利用草鱼为对象检测黄芩苷对嗜水气单胞菌增殖的影响。[结果] 黄芩苷在体外对嗜水气单胞菌有明显的抑菌效果,通过对生物膜的研究发现黄芩苷对生物膜形成具有抑制作用,并同时抑制其运动性。同时黄芩苷可以破坏细胞结构,并增加了细胞膜通透性。体内实验结果显示黄芩苷对嗜水气单胞菌具有清除作用,且具有一定的浓度依赖性。[结论] 黄芩苷在体内外均具有抑制嗜水气单胞菌增殖的作用,有望在水产养殖病害防治工作中得到应用。     

黄芩苷对结肠癌细胞凋亡的影响及作用机制

黄芩苷在多种肿瘤中具有较高的抗肿瘤活性,然而,其在结肠癌中的抗肿瘤作用尚不清楚。本研究考察了黄芩苷对人结肠癌细胞系RKO的增殖和凋亡的影响,并探讨了其相关作用机制。研究发现,黄芩苷可按照剂量依赖性方式和时间依赖性方式抑制结肠癌细胞增殖及集落形成能力。流式细胞术显示,与对照细胞相比,黄芩苷处理后的RKO细胞的凋亡率显著增加(5.6%vs 33.6%)。RT-PCR和Western blotting检测显示,黄芩苷处理可显著增加结肠癌RKO细胞中DKK1 (Wnt信号通路的关键负调节因子) mRNA和蛋白表达水平。相反,黄芩苷处理则显著抑制结肠癌RKO细胞中c-Myc和β-catenin (DKK1的下游靶基因)的m RNA和蛋白表达。敲低DKK1后明显阻断了黄芩苷诱导的结肠癌细胞中DKK1蛋白的上调。此外,敲低DKK1逆转了黄芩苷对其下游基因c-Myc和β-catenin的抑制作用。黄芩苷处理后,结肠癌细胞中miR-217的表达显著下调。RT-PCR和Western blotting结果显示,下调miR-217显著促进DKK1的mRNA和蛋白表达。综上所述,本研究表明黄芩苷可通过抑制结肠癌细胞增殖并诱导细胞凋亡来发挥其抗肿瘤作用,黄芩苷通过激活结肠癌细胞中DKK1来抑制Wnt信号通路。此外,黄芩苷通过下调结肠癌细胞中miR-217的表达来上调DKK1的表达,从而起到抗癌作用。     

黄芩配伍川贝母后黄芩中主要化学成分含量变化及抗肺炎作用研究

本文旨在探究黄芩川贝母不同比例配伍后对黄芩中主要化学成分含量影响及等比配伍后抗肺炎作用.将黄芩川贝母按3∶0、3∶1、3∶2、3∶3、2∶3、1∶3、0∶3比例配伍后,水提取,高效液相色谱法测定黄芩苷、汉黄芩苷、黄芩素、汉黄芩素含量.选择健康ICR小鼠36只,随机分为6组,分别为空白组、LPS组、阳性药组、黄芩组、川贝...     

黄芩苷对巨细胞病毒神经系统感染小鼠学习记忆功能及海马中细胞凋亡的调节作用

新生儿感染巨细胞病毒(Cytomegalovirus,CMV)能够引起中枢神经系统不可逆损害,遗留神经功能缺损,危害较大,但缺乏有效的防治手段。黄芩苷是中药材黄芩中的黄酮类活性物质,具有抗凋亡、抗氧化、抗炎等功能,对新生大鼠缺血缺氧性脑损伤具有保护作用。基于此,本研究将黄芩苷用于小鼠巨细胞病毒(Mouse cytomegalovirus,MCMV)感染新生KM小鼠的干预,并探究黄芩苷对MCMV感染后中枢神经损害的保护作用。为研究黄芩苷对MCMV神经系统感染小鼠学习记忆功能及海马中细胞凋亡的调节作用,本研究将新生KM小鼠随机分为对照组、MCMV组、黄芩苷组、黄芩苷+U0126组,后三组腹腔注射MCMV病毒悬液以获得MCMV神经系统感染模型,MCMV组给予生理盐水灌胃,黄芩苷组给予黄芩苷灌胃,黄芩苷+U0126组则给予黄芩苷灌胃及U0126腹腔注射。比较四组学习记忆功能指标及海马组织中MCMV载量、细胞凋亡率、凋亡基因表达量、信号通路基因表达量。结果显示:与对照组比较,MCMV组小鼠的逃避潜伏期明显延长(P0.05),穿平台次数明显减少(P0.05),海马组织中MCMV-DNA载量、细胞凋亡率及bax、cleaved-caspase-3的表达量明显增加(P0.05),海马组织中bcl-2、p-MEK1、p-ERK1/2的表达量明显降低(P0.05);与MCMV组小鼠比较,黄芩苷组小鼠的逃避潜伏期明显缩短(P0.05),穿平台次数明显增多(P0.05),海马组织中MCMV-DNA载量无明显变化(P0.05),海马组织的细胞凋亡率及bax、cleaved-caspase-3的表达量明显降低(P0.05),海马组织中bcl-2、p-MEK1、pERK1/2的表达量明显增加(P0.05);与黄芩苷组比较,黄芩苷+U0126组小鼠的逃避潜伏期明显延长(P0.05),穿平台次数明显减少(P0.05),海马组织中MCMV-DNA载量无明显变化(P0.05),海马组织的细胞凋亡率及bax、cleaved-caspase-3的表达量明显增加(P0.05),海马组织中bcl-2、p-MEK1、p-ERK1/2的表达量明显降低(P0.05)。综上,黄芩苷能够改善MCMV神经系统感染小鼠的学习记忆功能,通过激活MEK1/ERK1/2途径抑制海马中细胞凋亡是其可能的分子机制。     

黄芩苷对人肝癌细胞增殖抑制及放疗增敏作用

目的:探讨黄芩苷对人肝癌细胞Hep G2增殖抑制及放疗增敏作用。方法:以人肝癌细胞株Hep G2为研究对象,用CCK-8法和流式细胞仪检测黄芩苷对肝癌细胞增殖的影响和肝癌细胞放射敏感性的改变。结果:CCK-8法检测黄芩苷对Hep G2的生长有显著抑制作用且具有剂量依赖性,与阴性对照组对比差异有统计学意义(P0.05)。黄芩苷能使处于G0/G1、G2/M期的细胞减少,S期细胞增加。同时,黄芩苷对Hep G2放疗具有增敏作用。结论:黄芩苷可抑制人肝癌细胞增殖,可能与影响细胞周期有关;黄芩苷能增强肝癌细胞放射敏感性。     

Identification of Baicalin as an immunoregulatory compound by controlling T(H)17 cell differentiation

T(H)17 cells have been implicated in a growing list of inflammatory disorders. Antagonism of T(H)17 cells can be used for the treatment of inflammatory injury. Currently, very little is known about the natural compound controlling the differentiation of T(H)17 cells. Here, we showed that Baicalin, a compound isolated from a Chinese herb, inhibited T(H)17 cell differentiation both in vitro and in vivo. Baicalin might inhibit newly generated T(H)17 cells via reducing RORγt expression, and together with up-regulating Foxp3 expression to suppress RORγt-mediated IL-17 expression in established T(H)17 cells. In vivo treatment with Baicalin could inhibit T(H)17 cell differentiation, restrain T(H)17 cells infiltration into kidney, and protect MRL/lpr mice against nephritis. Our findings not only demonstrate that Baicalin could control T(H)17 cell differentiation but also suggest that Baicalin might be a promising therapeutic agent for the treatment of T(H)17 cells-mediated inflammatory diseases.     

Activating hydroxyl groups of polymeric carriers using 4-fluorobenzenesulfonyl chloride.

4-Fluorobenzenesulfonyl chloride (fosyl chloride), due to the strong electron-withdrawing property of its fluoride atom, is found to be an excellent activating agent for the covalent attachment of biologicals to a variety of solid supports (e.g. functionalized polystyrene microspheres, Sepharose beads, or cellulose rods and hollow fibers). This reagent reacts rapidly with primary or secondary hydroxyl groups, at ambient temperature and pressure, to form 4-fluorobenzenesulfonate leaving groups. The activated solid support can be used immediately or preserved for several months without loss of activity by freeze-drying or by storage at 4 degrees C in aqueous solution at pH 5. Enzymes, antibodies, avidin, and other biologicals can be covalently attached to the activated solid phase with excellent retention of biological function. Potential therapeutic applications of the fosyl chloride chemistry for bioselective separation of human lymphocyte subsets from whole blood and tumor cells from bone marrow are presented.     

Occupational allergy in the production of drugs

Quinazoline oxide--an intermediate in chlordiazepoxide synthesis--is the most potent contact allergen in the pharmaceutical industry. Penicillins proved to be potent allergens. Conditions of the technological process favor development of hypersensitivity to tetracyclines. No single case of allergy to erythromycin was noted. In case of employees hypersensitive to disulfiram and aminophylline cross reactions with compounds of similar structure were observed. The authors discuss also some problems concerning contact allergy in all persons occupationally dealing with various medicines.     

中国血液制品行业分析

血液制品是指血浆蛋白制品及相应的重组蛋白制品,目前可进行常规生产并应用于临床的主要有白蛋白、免疫球蛋白和凝血因子类三大系列产品。对我国血液制品行业进行了简要分析,总结了我国血液制品行业的发展历程,分析了我国血液制品的市场现状,概括了血液制品的主要生产技术,介绍了国内重点血液制品生产企业,预测了我国血液制品行业未来的发展趋势。     

Discovery of Baicalin as NDM-1 inhibitor: Virtual screening,biological evaluation and molecular simulation

The emergence and worldwide spreads of carbapenemase producing bacteria, especially New Delhi metallo-β-lactamase (NDM-1), has made a great challenge to treat antibiotics-resistant bacterial infections. It can hydrolyse almost all β-lactam antibacterials. Unfortunately, there are no clinically useful inhibitors of NDM-1. In this study, structure-based virtual screening method led to the identification of Baicalin as a novel NDM-1 inhibitor. Inhibitory assays showed that Baicalin possessed a good inhibition of NDM-1 with IC₅₀ values of 3.89 ± 1.1 μM and restored the susceptibility of E.coli BL21(DE3)/pET28a-NDM-1 to clinically used β-lactam antibiotics. Molecular docking and molecular dynamics simulations obtained a complex structure between the relatively stable inhibitor molecule Baicalin and NDM-1 enzyme. The results showed that the carboxyl group in Baicalin directly interacted with the Zn²⁺ in the active center of the enzyme, and the residues such as Glu152, Gln123, Met67, Trp93 and Phe70 in the enzyme formed hydrogen bonds with Baicalin to further stabilize the complex structure.     

Identification and characterization of a hypoallergenic ortholog of Ara h 2.01

Peanut (Arachis hypogaea L.), can elicit type I allergy becoming the most common cause of fatal food-induced anaphylactic reactions. Strict avoidance is the only effective means of dealing with this allergy. Ara h 2, a peanut seed storage protein, has been identified as the most potent peanut allergen and is recognized by approximately 90% of peanut hypersensitive individuals in the US. Because peanut has limited genetic variation, wild relatives are a good source of genetic diversity. After screening 30 Arachis duranensis accessions by EcoTILLing, we characterized five different missense mutations in ara d 2.01. None of these polymorphisms induced major conformational modifications. Nevertheless, a polymorphism in the immunodominant epitope #7 (S73T) showed a 56–99% reduction in IgE-binding activity and did not affect T cell epitopes, which must be retained for effective immunotherapy. The identification of natural hypoallergenic isoforms positively contributes to future immunological and therapeutic studies and peanut cultivar development. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The clearance of viruses and transmissible spongiform encephalopathy agents from biologicals

The viral and transmissible spongiform encephalopathy (TSE) safety of therapeutics of biological origin (biologicals) is greatly influenced by the nature and degree of variability of the source material and by the mode of purification. Plasma-derived and recombinant DNA products currently have good viral safety records, but challenges remain. In general, large enveloped viruses are easier to remove from biologicals than small 'naked' viruses. Monoclonal antibodies and recombinant DNA biopharmaceuticals are derived from relatively homogeneous source materials and purified by multistep schemes that are robust and amenable to scientific analysis and engineering improvement. Viral clearance is more challenging for blood and cell products, as they are complex and labile. Source selection (e.g. country of origin, deferral for CJD risk factors) currently occupies the front line for ensuring that biologicals are free of TSE agents, but robust methods for their clearance from products are under development.     

Mammalian sensitivity to elemental gold (Au degrees)

There is increasing documentation of allergic contact dermatitis and other effects from gold jewelry, gold dental restorations, and gold implants. These effects were especially pronounced among females wearing body-piercing gold objects. One estimate of the prevalence of gold allergy worldwide is 13%, as judged by patch tests with monovalent organogold salts. Eczema of the head and neck was the most common response of individuals hypersensitive to gold, and sensitivity can last for at least several years. Ingestion of beverages containing flake gold can result in allergic-type reactions similar to those seen in gold-allergic individuals exposed to gold through dermal contact and other routes. Studies with small laboratory mammals and injected doses of colloidal gold showed increased body temperatures, accumulations in reticular cells, and dose enhancement in tumor therapy; gold implants were associated with tissue injuries. It is proposed that Au degrees toxicity to mammals is associated, in part, with formation of the more reactive Au+ and Au3+ species.     

What are the immunological consequences of long-term use of biological therapies for juvenile idiopathic arthritis?

This review summarizes the immunological consequences of biological therapies used in juvenile idiopathic arthritis (JIA). For every frequently used biological agent the characteristics are clearly specified (molecular target, isotype, registered indication for JIA, route of administration, half-life, contraindication, very common side effects, expected time of response and average cost in the first year). The emphasis of this review is on the immunological side effects that have been encountered for every separate agent in JIA populations. For each agent these adverse events have been calculated as incidence per 100 patient-years for the following categories: serious infections, tuberculosis, malignancies, response to vaccination, new-onset autoimmune diseases and development of anti-drug antibodies. There are large differences in side effects between various agents and there is a clear need for an international and standardized collection of post-marketing surveillance data of biologicals in the vulnerable group of JIA patients. Such an international pharmacovigilance database, called Pharmachild, has now been started.