目的 探讨毛钩藤碱（hirsutine，HS）对β-淀粉样蛋白（Aβ）纤维化的影响。方法 体外孵育构建Aβ1-42淀粉样纤维化模型，硫黄素-T（ThT）染色分析Aβ1-42纤维化动力学曲线，透射电镜（TEM）、刚果红（CR）染色和圆二色谱（CD）观察其形态结构变化，8-苯胺-1-萘磺酸（ANS）染色检测疏水区域暴露，MTT、溶血和DCFH-DA染色实验评估Aβ1-42细胞毒性和细胞内ROS含量，分子对接实验分析HS与Aβ1-42相互作用。结果 HS可明显减弱ThT荧光强度（P1-42干预的SH-SY5Y细胞活性（P<0.05，P<0.01），降低溶血率（P&...

本文旨在探讨管花苷B （tubuloside B， Tub B） 对β-淀粉样蛋白 （amyloid β-protein， Aβ） 纤维化的抑制作用及潜在作用机制。采用体外孵育Aβ1-42建立蛋白质淀粉样纤维化模型， 利用硫黄素-T （thioflavin T， ThT）、刚果红 （Congo red， CR）、8-苯胺-1-萘磺酸 （8-anilino-1-naphthalene sulfonic acid， ANS） 染色和透射电子显微镜 （transmission electron microscope， TEM） 考察Tub B对Aβ1-42纤维形成的抑制作用; 圆二色谱 （circular dichroism， CD） 分析Tub B对Aβ1-42二级结构的影响; 3-（4，5-二甲基-2-噻唑）-2，5-二苯基溴化四氮唑噻唑蓝 [3-（4，5-dimethyl-2-thiazolyl）-2，5-diphenyl-2H-tetrazolium bromide， MTT] 和红细胞溶血实验研究Tub B对Aβ1-42诱导的细胞毒性的抑制作用; 2'，7'-二氯二氢荧光素二乙酸酯 （2'，7'-dichlorofluorescin diacetate， DCFH-DA） 染色检测Tub B对Aβ1-42诱导的细胞内活性氧 （reactive oxygen species， ROS） 含量的影响; 以及利用分子对接实验研究Tub B与Aβ1-42分子相互作用。结果显示， Tub B对Aβ1-42淀粉样纤维形成具有一定抑制作用， 可降低Aβ1-42二级结构中α-螺旋结构向β-折叠结构的转化， 减少疏水区域暴露， 减弱Aβ1-42引起的细胞毒性和红细胞溶血性， 降低细胞损伤。综上所述， Tub B能够抑制蛋白质淀粉样纤维形成， 且这种抑制作用可能与其抗氧化活性及与蛋白质分子间的氢键和疏水作用力有关。本研究的动物实验经空军军医大学动物实验伦理委员会批准 （批准号: 20190051）。

Abnormal aggregation and fibrillogenesis of amyloid-beta protein (A beta) can cause Alzheimer's disease (AD). Thus, the discovery of effective drugs that inhibit A beta fibrillogenesis in the brain is crucial for the treatment of AD. Luteoloside, as one of the polyphenolic compounds, is found to have a certain therapeutic effect on nervous system diseases. However, it remains unknown whether luteoloside is a potential drug for treating AD by modulating A beta aggregation pathway. In this study, we performed diverse biophysical and biochemical methods to explore the inhibition of luteoloside on A beta 1-42 which is linked to AD. The results demonstrated that luteoloside efficiently prevented amyloid oligomerization and cross-beta-sheet formation, reduced the rate of amyloid growth and the length of amyloid fibrils in a dose-dependent manner. Moreover, luteoloside was able to influence aggregation and conformation of A beta 1-42 during different fiber-forming phases, and it could disintegrate already preformed fibrils of A beta 1-42 and convert them into nontoxic aggregates. Furthermore, luteoloside protected cells from amyloid-induced cytotoxicity and hemolysis, and attenuated the level of reactive oxygen species (ROS). The molecular docking study showed that luteoloside interacted with A beta 1-42 mainly via Conventional Hydrogen Bond, Carbon Hydrogen Bond, Pi-Pi T-shaped, Pi-Alkyl and Pi-Anion, thereby possibly preventing it from forming the aggregates. These observations indicate that luteoloside, a natural anti-oxidant molecule, may be applicable as an effective inhibitor of A beta, and promote further exploration of the therapeutic strategy against AD.

Ten new proansamycin B congeners (1-10) together with one known (11) were isolated and characterized on the basis of 1D and 2D NMR spectroscopic and HRESIMS data from the Amycolatopsis mediterranei S699 DeltaPM::rifR+rif-orf19 mutant. Compounds 8 and 9 featured with six-membered ring and five-membered ring hemiketal, respectively. Compounds 1, 2, and 9 displayed antibacterial activity against MRSA (methicillin-resistant Staphylococcus aureus), with the MIC (minimal inhibitory concentration) values of 64, 8, and 128g/mL, respectively. Compound 1 showed significant cytotoxicity against MDA-MB-231, HepG2 and Panc-1 cell lines with IC50 (half maximal inhibitory concentration) values of 2.3±0.2, 2.5±0.3 and 3.8±0.5muM, respectively. © 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.

目的 研究毛蕊花糖苷对中波紫外线(UVB)照射所致小鼠皮肤损伤的保护作用。方法 将Balb/c小鼠随机分为正常对照组、UVB模型组、基质+UVB组、1%毛蕊花糖苷+UVB组、5%毛蕊花糖苷+UVB组、5%维生素E+UVB组,每组10只。除正常对照组外,其余4组

目的对剑叶龙血树内生链霉菌S009中抗菌活性成分进行研究。方法采用Sephadex LH-20、反相柱色谱、硅胶柱层析及HPLC对S009菌株的发酵产物进行分离纯化,并通过MS、NMR等波谱技术鉴定其结构。结果从S009菌株中分离并鉴定了4个大环四重内

Rifamycin W, the most predominant intermediate in the biosynthesis of rifamycin, needs to undergo polyketide backbone rearrangement to produce rifamycin B via an oxidative cleavage of the C-12/C-29 double bond. However, the mechanism of this putative oxidative cleavage has not been characterized yet. Rif-Orf5 (a putative cytochrome P450 monooxygenase) was proposed to be involved in the cleavage of this olefinic moiety of rifamycin W. In this study, the mutant strain Amycolatopsis mediterranei S699 Delta rif-orf5 was constructed by in-frame deleting the rif-orf5 gene to afford thirteen rifamycin W congeners (1-13) including seven new ones (1-7). Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and high-resolution ESI mass spectra. Presumably, compounds 1-4 were derivatized from rifamycin W via C-5/C-11 retro-Claisen cleavage, and compounds 1-3, 9 and 10 featured a hemiacetal. Compounds 5-7 and 11 showed oxygenations at various sites of the ansa chain. In addition, compounds 1-3 exhibited antibacterial activity against Staphylococcus aureus with minimal inhibitory concentration (MIC) values of 5, 40 and 0.5 mu g/mL, respectively. Compounds 1 and 3 showed modest antiproliferative activity against HeLa and Caco-2 cells with half maximal inhibitory concentration (IC50) values of about 50 mu M.

本文旨在通过网络药理学和分子对接方法探讨丹参-丹皮活性成分治疗脑卒中的潜在分子机制。首先基于中药系统药理学分析平台筛选丹参、丹皮的活性成分及其作用靶点,利用CTD、TTD和GeneCards数据库收集脑卒中相关靶点。然后将药物和疾病靶点取交集,借助STRING数据库获取靶点间相互作用关系,利用R语言的ClusterProfiler包对其进行生物功能和通路富集分析。最后,通过Cytoscape软件构建蛋白质-蛋白质相互作用和成分-靶点-通路网络图,并利用AutoDock Vina软件对网络中的关键靶点及对应成分进行分子对接验证。结果显示丹参-丹皮成分作用于脑卒中的靶点67个,GO分析显示其主要参与脂多糖应答,细菌来源的分子反应,氧化应激等生物学过程。KEGG通路富集共得到149条通路（P＜0.05）,主要涉及AGE-RAGE信号通路、IL-17信号通路、TNF信号通路等。分子对接结果显示,筛选的主要活性成分与其对应靶蛋白均具有较好的结合活性。综上,本研究通过网络药理学预测了丹参-丹皮治疗脑卒中可能的药效物质基础及其作用机制,为进一步挖掘其药效成分和临床扩大使用范围提供科学依据。

Proansamycin X, a hypothetical earliest macrocyclic precursor in the biosynthesis of rifamycin, had never been isolated and identified. According to bioinformatics analysis, it was proposed that RifT (a putative NADH-dependent dehydrogenase) may be a candidate target responsible for the dehydrogenation of proansamycin X. In this study, the mutant strain Amycolatopsis mediterranei S699 Delta rifT was constructed by deleting the rifT gene. From this strain, eleven 8-deoxy-rifamycin derivatives (1-11) and seven known analogues (12-18) were isolated. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and high-resolution ESI mass spectra. Compound 1 is a novel amide N-glycoside of seco-rifamycin. Compounds 2 and 3 feature conserved 11,12-seco-rifamycin W skeleton. The diverse post-modifications in the polyketide chain led to the production of 4-11. Compounds 2, 3, 5, 6, 13 and 15 exhibited antibacterial activity against Staphylococcus aureus (MIC (minimal inhibitory concentration) values of 10, 20, 20, 20, 40 and 20 mu g/mL, respectively). Compounds 14, 15, 16, 17 and 18 showed potent antiproliferative activity against KG1 cells with IC50 (half maximal inhibitory concentration) values of 14.91, 44.78, 2.16, 18.67 and 8.07 mu M, respectively.

目的研究松果菊苷防晒乳膏剂的制备工艺,并对其质量进行评价。方法通过正交试验对松果菊苷防晒乳膏剂基质处方进行优化,优选出最佳处方;通过紫外扫描法建立质量评价标准。结果优选出松果菊苷防晒乳膏剂的最佳处方为松果菊苷5%、硬脂酸10%、单硬脂酸甘油酯5%、液状石蜡5%、白凡士林10%、三乙醇胺4%、氮酮3%、尼泊金乙酯0.1%。按照该处方制备的乳膏剂在最大吸收波长334 nm处的吸光度值相对稳定。结论松果菊苷防晒乳膏剂的制备工艺简单,所得制剂性质稳定,质量可控,测定方法简便、快捷、准确,为后期进一步研究和应用奠定了基础。