盐酸诺拉曲塞的合成

2-溴-4-硝基甲苯经催化氢化、与水合氯醛和盐酸羟胺反应、环合制得4-溴-5-甲基靛红,再经Baeyer-Villiger反应、甲酯化、与盐酸氯甲脒环合、Ullmann反应、成盐结晶制得胸苷酸合成酶抑制剂盐酸诺拉曲塞二水合物,总收率为8%。     

人参皂苷Rb1抑制β淀粉样蛋白25-35诱导的皮层神经元tau蛋白过度磷酸化

目的探讨人参皂苷Rb1对凝聚态β-AP_25-35诱导的胎鼠皮层神经元tau蛋白过度磷酸化的影响及其可能的作用机制。方法通过蛋白免疫印迹法和免疫细胞化学染色法检测神经元tau蛋白磷酸化水平、总tau蛋白水平和糖原合成酶3β(GSK-3β)的蛋白表达水平。结果凝聚态β-AP_25-35(20 μmol·L^-1)作用于皮层神经元12 h，tau蛋白磷酸化水平和总tau蛋白水平均增高，同时GSK-3β蛋白表达也增多。用人参皂苷Rb1或GSK-3β特异性抑制剂氯化锂预处理后，凝聚态β-AP_25-35诱导的tau蛋白的过度磷酸化受到明显抑制，同时GSK-3β的表达也降低。结论人参皂苷Rb1可通过抑制GSK-3β的表达来抑制凝聚态β-AP_25-35诱导的皮层神经元tau蛋白的过度磷酸化。     

肠安康新组方抗溃疡性结肠炎大鼠的机制研究

目的研究肠安康新组方抗溃疡性结肠炎(UC)大鼠可能的作用机制。方法制备三硝基苯磺酸(TNBS)/乙醇诱导溃疡性结肠炎(UC)大鼠模型,动物随机分为9组:正常对照组、模型对照组、柳氮磺胺吡啶(SASP)组、肠安康新组方口服给药组(1.12、0.56、0.28 g.kg-1)、肠安康新组方结肠定位给药组(1.12、0.56、0.28 g.kg-1)。造模后24 h开始给药,每天1次,连续给药7 d,从造模开始至实验结束共9d。实验结束后紫外分光光度法测诱导型一氧化氮合酶(iN-OS)活性、一氧化氮(NO)含量,ELISA法测白介素-8(IL-8)含量,免疫组化法检测c-Jun表达。结果与模型组相比,肠安康新组方各给药组均可改善升高的iNOS、NO、IL-8、c-Jun。结论肠安康新组方抗UC作用可能与抑制炎症因iN-OS、NO、IL-8的产生和c-Jun的激活有关。     

nNOS参与OGD介导的促神经干细胞增殖效应

目的：体外研究脑缺血促神经发生的机制。 方法： 体外培养神经干细胞（neural stem cells,NSCs）与海马神经元,并采用氧糖剥夺模型（oxygen and glucose deprivation, OGD）模拟在体缺血,通过RT-PCR、Western blot、免疫细胞化学、酶活性测定、亚硝酸盐/硝酸盐（nitrite/nitrate,NOx） 含量测定等多种方法研究神经干细胞的生物学行为以及介导这种效应的分子机制。结果： （1）OGD通过直接和间接（神经元）作用增加神经干细胞中BrdU＋ 细胞比例。（2）OGD上调神经干细胞中神经元型一氧化氮合酶（neuronal nitric oxide synthase,nNOS）并下调神经元中nNOS,且都有利于神经干细胞增殖。（3）采用nNOS基因敲除小鼠来源的神经干细胞以及神经元（用于共培养）进行实验,发现OGD并不能升高神经干细胞中BrdU＋ 细胞比例。 结论：神经干细胞和神经元中nNOS水平变化共同参与了OGD诱导的促神经干细胞增殖效应。     

Effects of rhein on human articular chondrocytes in alginate beads

This study was designed to investigate the effects of rhein, the active metabolite of diacerhein, on the metabolic functions of human chondrocytes cultured in alginate beads.Enzymatically isolated osteoarthritic (OA) chondrocytes were cultured in alginate beads in a well-defined culture medium for 12 days. Rhein was tested in a range of concentrations comprised between 10(-7) and 4 x 10(-5)M, in the presence or absence of 10(-10)M IL-1beta. Interleukin (IL)-6 and -8, macrophage inflammatory protein (MIP-1beta), stromelysin-1 (MMP-3), aggrecan (AGG), tissue inhibitor of metalloproteinases-1 (TIMP-1), prostaglandin E(2) (PGE(2)) and nitric oxide (NO) productions were assayed. Cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) mRNA steady-state levels were also quantified. In the basal condition, 10(-5)M rhein increased by 46.5% the production of AGG, decreased by 17-30% the production of IL-6, MMP-3, NO and MIP-1beta but enhanced by 50% the production of PGE(2). IL-1beta increased IL-6, IL-8, MIP-1beta, NO, PGE(2) and MMP-3 productions, but inhibited AGG and TIMP-1 synthesis. Rhein partially reversed the effect of IL-1beta on TIMP-1 and NO production, had no effect on AGG, IL-6 and MIP-1beta production, but up-regulated the IL-1beta stimulated PGE(2) production. The COX-2 and iNOS mRNA levels and IL-8 production were not modified by rhein.Overall, these results contribute to explain the clinical efficiency of rhein and give new information on its mechanisms of action.     

雏鸡耳蜗中的一氧化氮合成酶分布

应用冰冻切片组织化学技术，以还原型尼克酰胺腺嘌呤二核苷酸磷酸-黄递酶特异性地确定一氧化氮合成酶（NOS）在小鸡耳蜗中存在，观察其分布情况，发现听毛细胞底部颗粒较集中，染色深，毛细胞周围亦有散在颗粒，基底乳头近端与远端染色强弱相似。阳性反应神经纤维连接毛细胞底部。螺旋神经节细胞胞浆中有大量的蓝色颗粒，细胞核无着色，这些细胞大小均匀，呈圆形或椭圆形，周围有多量阳性神经纤维，提示可能为神经性NOS。血管盖内皮细胞胞浆中酶活性较强。对这些分布特点和意义进行了讨论。     

三七总皂苷对小鼠柯萨奇B3病毒性心肌炎诱导型一氧化氮合酶的影响

目的：探讨三七总皂苷对小鼠柯萨奇B3病毒所致病毒性心肌炎模型中诱导型一氧化氮合酶（iNOS）表达的影响,为病毒性心肌炎的治疗寻找新的理论依据。方法：选用近交系4～6周龄雄性BALB／C小鼠84只,随机分为3组：空白对照组（C组）24只,心肌炎组（V组）30只,治疗组（T组）30只。于病毒接种后第8天、第15天、第21天分别采血后处死小鼠并留取心脏标本,采用免疫组化法检测心肌iNOS蛋白表达,硝酸还原酶法测定血清NO含量,光镜及透射电镜观察心肌组织病理及细胞超微结构改变。结果：（1）V组和T组小鼠心肌细胞iNOS免疫组化染色表达呈阳性,c组iNOS免疫组化染色阴性;（2）T组与V组比较,心肌细胞iNOS表达在第15天及第21天明显降低,差异有统计学意义（P〈0．05、P〈0．01）;（3）T组在第15天及第21天血清NO含量较V组明显降低（P〈0．05）;（4）光镜下T组炎症细胞浸润较V组轻,炎症积分在第15天及第21天明显低于V组（P〈0．05、P〈0．01）;（5）电镜下V组及T组可见肌原纤维溶解断裂,线粒体膜消失,含溶酶体丰富的单核巨噬细胞浸润,c组小鼠心肌未见上述变化。结论：三七总皂苷可降低小鼠病毒性心肌炎iNOS的表达,从而减少NO释放,可能对病毒性心肌炎有一定治疗作用。     

PGK1-coupled HSP90 stabilizes GSK3β expression to regulate the stemness of breast cancer stem cells

Objective: Glycogen synthase kinase-3β(GSK3β) has been recognized as a suppressor of Wnt/β-catenin signaling, which is critical for the stemness maintenance of breast cancer stem cells. However, the regulatory mechanisms of GSK3β protein expression remain elusive.Methods: Co-immunoprecipitation and mass spectral assays were performed to identify molecules binding to GSK3β, and to characterize the interactions of GSK3β, heat shock protein 90(Hsp90), and co-chaperones. The role of PGK1 in Hsp90 ch...     

Herbal medicines for the prevention of alcoholic liver disease: A review

Ethnopharmacological relevance

Long-term excess alcohol exposure leads to alcoholic liver disease (ALD)—a global health problem without effective therapeutic approach. ALD is increasingly considered as a complex and multifaceted pathological process, involving oxidative stress, inflammation and excessive fatty acid synthesis. Over the past decade, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of ALD, due to their multiple targets and less toxic side effects. Several herbs, such as Cnidium monnieri (L.) Cusson (Apiaceae), Curcuma longa L. (Zingiberaceae) and Pueraria lobata (Willd.) Ohwi (Leguminosae), etc., have been shown to be quite effective and are being widely used in China today for the treatment of ALD when used alone or in combination.

Aim of the review

To review current available knowledge on herbal medicines used to prevent or treat ALD and their underlying mechanisms.

Materials and methods

We used the pre-set searching syntax and inclusion criteria to retrieve available published literature from PUBMED and Web of Science databases, all herbal medicines and their active compounds tested on ALD induced by both acute and chronic alcohol ingestion were included.

Results

A total of 40 experimental studies involving 34 herbal medicines and (or) active compounds were retrieved and reviewed. We found that all reported extracts and individual compounds from herbal medicines/natural plants could be beneficial to ALD, which might be attributed to regulate multiple critical targets involved in the pathways of oxidation, inflammation and lipid metabolism.

Conclusions

Screening chemical candidate from herbal medicine might be a promising approach to drug discovery for the prevention or treatment of ALD. However, further studies remain to be done on the systematic assessment of herbal medicines against ALD and the underlying mechanisms, as well as their quality control studies.