紫草色素的研究

紫草色素原植物系紫草科Broaginaceae几种植物的根，又称紫根色素。该研究首次用人工栽培的硬紫草(Lithospermum erythrohizon Sieb.)的根，作了加工工艺和特性的研究。产品得率近1％，色价E 1^1Q5nm达150以，卫生指标符合有关规定，是种理想的脂溶性红色素。     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

固定化紫草细胞生产紫草宁衍生物

用海藻胶包埋紫草细胞,在紫草色素生产培养基M_9中,常温、黑暗下培养不同时间,收集培养液并提取色素,进行紫外—可见全波长分光光度扫描和TLC分析。结果表明:固定化紫草细胞可连续分泌紫草色素,其主要成分与天然成分基本相同,产量已达到一定水平。此外对海藻胶包埋条件、固定化珠粒的稳定性以及1L固定化植物细胞反应器生产紫草色素工艺进行了讨论。     

紫草抗氧化成分的提取及其活性研究

分别用石油醚、三氯甲烷和乙醇依次提取紫草成分 ,用OSI仪测定了三种提取物对猪油氧化稳定性的影响 ,发现石油醚提取成分 (LE - pet)和三氯甲烷提取成分 (LE -chl)有明显的抗氧化活性 ,添加到猪油中后 ,w =0 0 2 %时 ,猪油的氧化稳定性比空白样品提高了约 1倍。对LE -pet和LE -chl进行薄层层析分离鉴定 ,得到三种化合物 :β ,β 二甲基丙烯酰紫草醌 (Ⅰ)、乙酰紫草醌 (Ⅱ)和紫草醌 (Ⅲ)。对它们的抗氧化活性进行测试 ,化合物Ⅱ和Ⅲ表现出明显的抗氧化活性 ,当w(Ⅱ)=0 .0 6 %、w(Ⅲ) =0 0 6 %时 ,猪油的氧化稳定性分别提高了 6 0 4和 3 94倍。化合物Ⅰ、Ⅱ、Ⅲ与VE均有较强的协同作用 ,化合物Ⅰ、Ⅱ、Ⅲ的质量分数为 0 .0 2 %与VE 的质量分数为 0 0 2 %共同使用时 ,其抗氧化协同系数 (SE)分别为 81 4(Ⅰ)、5 2 7(Ⅱ)和 132 6 (Ⅲ )     

紫草在柞丝绸织物染色中的应用

对紫草用于柞蚕丝织物的染色性能进行了探讨。用乙醇提取紫草色素,选取染液体积分数、pH值、温度和时间4个因素,通过正交试验及单因素分析试验,优化出紫草上染柞蚕丝织物的最佳工艺条件为:浴比1∶40,染液体积分数8%,pH 6,温度80℃,时间60 min。通过不同媒染剂(Al3+、Fe2+、Cu2+)媒染处理,得到不同颜色的织物。通过对染色织物耐水洗及耐摩擦色牢度的检测得出,紫草上染柞蚕丝织物色牢度优良,直接染色和媒染均达到3级以上。     

高效液相色谱法同时测定紫草素及其衍生物

建立了高效液相色谱法同时测定紫草中的紫草素、去氧紫草素、异丁酰基紫草素、β,β-二甲基丙烯酰基紫草素、异戊酰基紫草素和2-甲基正丁酰基紫草素等萘醌类衍生物含量的方法。该方法简便、快速、线性范围宽、适应性好,可用于对紫草药材及紫草提取物中的萘醌类衍生物的含量测定和质量控制。     

超声波对新疆紫草悬浮培养细胞生长和紫草素合成的影响

探讨了超声波功率、超声波处理时间对新疆紫草细胞生长和紫草素合成的影响. 研究结果表明,超声波对悬浮培养的新疆紫草细胞生长有促进作用,低功率长时间或高功率短时间的超声处理对细胞生长比较有利. 在优化条件下(200 W超声处理1 min),培养结束时的生物量比对照提高61%. 超声波也可以提高新疆紫草悬浮培养细胞的紫草素含量和产量,接种后即进行超声波处理,超声波功率密度为39.9 mW/cm3、超声时间为3 min时,细胞紫草素含量和产量最高,达到2.72%和294 mg/L,分别比对照组提高了64%和135%. 超声波是通过提高细胞苯丙氨酸解氨酶的活力来强化紫草素的生物合成途径.     

Design,Synthesis, and Biological Evaluation of Shikonin and Alkannin Derivatives as Potential Anticancer Agents via a Prodrug Approach

To minimize the cytotoxicity of shikonin and alkannin that arises through the generation of reactive oxygen species (ROS) and alkylation of the naphthazarin ring, two series of novel core‐scaffold‐modified shikonin and alkannin derivatives were designed. These derivatives, which differ in their configurational and positional isomerism (R‐, S‐, and 2‐ and 6‐isomers) were synthesized in high enantiomeric excess (>99 % ee). The selectivity of the dimethylated derivatives was significantly higher than the parent shikonin in vitro, but some side effects were still observed in vivo. Surprisingly, the dimethylated diacetyl derivatives with poor anticancer activity in vitro showed tumor‐inhibiting effects similar to paclitaxel without any toxicity in vivo. The anticancer activity of these derivatives is in agreement with their low ROS generation and alkylating capacity, emphasizing their potential as prodrugs. This strategy provides means to address the nonspecific cytotoxicity of naphthazarin analogues toward normal cells.     

亚临界水萃取及大孔树脂分离纯化制备紫草素

以新疆紫草为研究对象,考察亚临界水的动态循环和静态平衡两种萃取方式对紫草素提取率的影响。选取不同极性的大孔树脂和有机溶剂对提取液中的紫草素进行吸附、解析实验;使用高效液相-蒸发光散射(HPLC-ELSD)技术分析样品的纯度。结果显示:10MPa、120℃、1.39cm3/s的流量,动态循环萃取8min,紫草素提取率最高是0.216%;静态平衡萃取16min,紫草素提取率最高是0.198%。DA-201大孔树脂对紫草素的吸附效果最佳,恒温摇床振荡吸附24h,吸附率是89.7%;丙酮的解析效果最好,能够将93.2%的紫草素解析出来,且速率较快。经大孔树脂吸附分离后,紫草素的纯度由27.31%提高至85.07%。实验表明,亚临界水萃取、大孔树脂吸附分离能够有效制备纯度较高的紫草素。     

新疆紫草的超声波强化提取

对新疆紫草色素进行了超声提取的研究,探讨了超声波功率、液固比、提取温度、原料粒度和超声作用时间对色素提取效果的影响,得到超声提取新疆紫草色素的优化工艺参数为：80目(180 mm)的新疆紫草根粉末,液固比为12 mg/L,在50℃水浴中超声处理25 min,超声波功率1800 W,提取率可达到87%.