黄连属植物愈伤组织诱导及生物碱产生

对6种黄连属药用植物进行了愈伤组织诱导和培养,并用薄层层析和高效液相色谱法分析比较了愈伤组织和原生药中小檗碱、药根碱、黄连碱、巴马丁和表小檗碱等成分。     

海南野扇花中甾体生物碱的化学研究

从黄杨科野扇花属植物海南野扇花(Sarcococca vagans Stapf)的根中分离得到6个甾体生物碱,经波谱分析及理化常数测定,确定其结构分别为帕其沙明A(pachysamine A,I),矮陀陀碱F(axilarine F,II),海南野扇花碱A～D(sarcovagine A～D,II～VI)。其中,化合物II～VI为新的甾体生物碱。     

De novo production of the plant-derived alkaloid strictosidine in yeast

The monoterpene indole alkaloids are a large group of plant-derived specialized metabolites, many of which have valuable pharmaceutical or biological activity. There are ∼3,000 monoterpene indole alkaloids produced by thousands of plant species in numerous families. The diverse chemical structures found in this metabolite class originate from strictosidine, which is the last common biosynthetic intermediate for all monoterpene indole alkaloid enzymatic pathways. Reconstitution of biosynthetic pathways in a heterologous host is a promising strategy for rapid and inexpensive production of complex molecules that are found in plants. Here, we demonstrate how strictosidine can be produced de novo in a Saccharomyces cerevisiae host from 14 known monoterpene indole alkaloid pathway genes, along with an additional seven genes and three gene deletions that enhance secondary metabolism. This system provides an important resource for developing the production of more complex plant-derived alkaloids, engineering of nonnatural derivatives, identification of bottlenecks in monoterpene indole alkaloid biosynthesis, and discovery of new pathway genes in a convenient yeast host.Monoterpene indole alkaloids (MIAs) are a diverse family of complex nitrogen-containing plant-derived metabolites (1, 2). This metabolite class is found in thousands of plant species from the Apocynaceae, Loganiaceae, Rubiaceae, Icacinaceae, Nyssaceae, and Alangiaceae plant families (2, 3). Many MIAs and MIA derivatives have medicinal properties; for example, vinblastine, vincristine, and vinflunine are approved anticancer therapeutics (4, 5). These structurally complex compounds can be difficult to chemically synthesize (6, 7). Consequently, industrial production relies on extraction from the plant, but these compounds are often produced in small quantities as complex mixtures, making isolation challenging, laborious, and expensive (8–10). Reconstitution of plant pathways in microbial hosts is proving to be a promising approach to access plant-derived compounds as evidenced by the successful production of terpenes, flavonoids, and benzylisoquinoline alkaloids in microorganisms (11–19). Microbial hosts can also be used to construct hybrid biosynthetic pathways to generate modified natural products with potentially enhanced bioactivities (8, 20, 21). Across numerous plant species, strictosidine is believed to be the core scaffold from which all 3,000 known MIAs are derived (1, 2). Strictosidine undergoes a variety of redox reactions and rearrangements to form the thousands of compounds that comprise the MIA natural product family (Fig. 1) (1, 2). Due to the importance of strictosidine, the last common biosynthetic intermediate for all known MIAs, we chose to focus on heterologous production of this complex molecule (1). Therefore, strictosidine reconstitution represents the necessary first step for heterologous production of high-value MIAs.Open in a separate windowFig. 1.Strictosidine, the central intermediate in monoterpene indole alkaloid (MIA) biosynthesis, undergoes a series of reactions to produce over 3,000 known MIAs such as vincristine, quinine, and strychnine.     

口虾蛄总生物碱对人鼻咽癌CNE-2Z细胞周期与凋亡的影响

提取口虾蛄总生物碱并观察其对人鼻咽癌CNE-2Z细胞增殖、凋亡的影响。方法 酸提碱沉法处理口虾蛄,沉淀部分以乙酸乙酯萃取;不同浓度的口虾蛄总生物碱处理CNE-2Z细胞,CCK-8法、平板克隆形成实验检测细胞增殖能力的影响;流式细胞术检测细胞周期分布的影响;蛋白免疫印迹实验检测Caspase8蛋白表达的变化。结果 口虾蛄总生物碱能明显抑制CNE-2Z细胞的增殖,降低克隆形成能力,使细胞周期阻滞于S期;Caspase8蛋白表达水平随着口虾蛄总生物碱浓度增高而降低,有一定的剂量依赖。结论 口虾蛄总生物碱抗CNE-2Z细胞的作用可能通过抑制细胞增殖、诱导细胞周期阻滞及细胞凋亡等发生。     

海洋来源真菌草酸青霉(Penicillium oxalicum)次级代谢产物的分离与鉴定

目的研究海洋来源真菌草酸青霉(Penicillium oxalicum)的次级代谢产物。方法采用重结晶、硅胶柱色谱、Sephadex LH-20柱色谱、开放ODS柱色谱等方法进行分离纯化;根据理化性质及光谱数据确定化合物的结构。结果分离得到10个化合物,分别鉴定为N-acetyl-hydrazinobenzoic acid(1)、N-[2-cis-(4-hydroxyphenyl)ethenyl]formamide(2)、p-hydroxyphenylacetamide(3)、penipanoid A(4)、penipanoid C(5)、2-(4-hydroxybenzyl)quinazolin-4(3H)-one(6)、oxaline(7)、meleagrin(8)、(3R,4R)-3,4,8-trihydroxy-3,4-dihydro-1(2H)-naphthalenone(9)和(3R,4R)-3,4,6,8-tetrahydroxy-3,4-dihydro-1(2H)-naphthalenone(10)。结论化合物1为新天然产物,化合物9、10为首次从青霉属真菌中分离得到。     

苦豆子生物碱现代药学研究进展

苦豆子是我国地道天然中药,具有确切的药理活性和较高的应用价值。本文就苦豆子生物碱的化学成分、制剂、质量控制、分离纯化、药理、毒理、药物动力学七个方面,综述近年来的研究进展,为苦豆子生物碱及制剂的开发应用提供参考。     

扁板海绵属化学成分及生物活性研究进展

扁板海绵属（Plakortis Schulze）海绵次生代谢产物丰富,类型多样,主要含有过氧化物、内酯、呋喃环、鞘糖脂和生物碱等类型的化学成分,具有独特的生物活性,包括抗肿瘤、抗微生物、激活肌浆网Ca²⁺-ATP酶、抗疟和免疫抑制等作用,具有广阔的开发应用前景。对该属海绵化合物类型进行分类归纳,并对其主要药理活性研究进行综述,为该属海绵进一步研究开发提供参考。     

基于均匀设计法对酸枣仁镇静催眠有效组分的配伍研究

目的 优选酸枣仁中3种具有镇静催眠作用的主要有效组分（总皂苷、总黄酮、总生物碱）最佳配伍。方法 采用均匀设计法将70只小鼠随机分为7组,分别为对照组及给药A～F组,观察各组小鼠自主活动情况;采用阈上剂量戊巴比妥钠（45 mg/kg）协同睡眠试验,以小鼠的睡眠潜伏期和睡眠时间为评价指标,筛选酸枣仁镇静催眠有效组分的最佳配伍。对所得有效组分最佳配伍的药效进行比较和验证实验。结果 与对照组比较,给药A、C、E组小鼠自主活动减少（P＜0.05、0.01）,C、D组小鼠站立次数略有减少（P＜0.05）。在阈上剂量戊巴比妥钠协同试验中,给药组C～F睡眠潜伏期显著缩短（P＜0.01）,B～F组睡眠时间显著延长（P＜0.01）。经多元统计分析,酸枣仁镇静催眠有效组分的最佳配伍组合为总皂苷200 mg/kg、总黄酮0 mg/kg、总生物碱20 mg/kg。结论 应用均匀设计与药效学相结合确定中药有效组分配伍的方法是可行的。验证实验表明,酸枣仁有效组分的最佳配伍组合可以达到与原药材相同的疗效。