正交实验优选阿魏胶囊的提取工艺

目的:优选阿魏胶囊的提取工艺.方法:以没食子酸含量和浸膏得率为综合评价指标,采用正交试验设计优选出阿魏胶囊的水提取工艺.以厚朴酚、和厚朴酚含量和浸膏得率为综合评价指标,采用正交试验设计优选出阿魏胶囊的乙醇提取工艺.结果:优选出的水提工艺为:药材加10倍量水,回流提取2次,每次1.5h.优选出的醇提工艺为:80%乙醇回流提取2次,每次1.5h,每次加醇量为药材量的6倍.结论:优选得到的提取工艺稳定、合理、可行.     

不同厂家藿香正气水质量比较研究及分析

目的:比较目前市场上流通的5个厂家藿香正气水的质量状况。方法:对5个厂家5批次药品进行装量差异和乙醇含量等常规检查,采用改进的高效液相色谱(HPLC)法测定药品中厚朴酚与和厚朴酚的含量,色谱柱为SHIMADZU HPLC-20AT ODSC18(150mm×4.6mm)柱,流动相为乙腈∶水=60∶40(2%冰乙酸),检测波长294nm。结果:改进HPLC方法测得和厚朴酚(r=0.9998)与厚朴酚(r=0.9999)在1～100mg·L-1范围内线性关系良好,厚朴酚的平均回收率为99.02%,RSD=1.78%;和厚朴酚的平均回收率为99.15%,RSD=0.97%。不同厂家生产的藿香正气水装量差异、乙醇含量、厚朴酚与和厚朴酚总量均符合2005年版《中国药典》中相关规定,但厚朴酚与和厚朴酚的含量差异较大。结论:建议进一步研究生产工艺,稳定原料药,并制定出科学、统一的质量标准。     

Honokiol induces paraptosis and apoptosis and exhibits schedule-dependent synergy in combination with imatinib in human leukemia cells

Honokiol, an active component isolated and purified from Chinese traditional herb magnolia, has been shown to inhibit growth and induce apoptosis in different cancer cell lines. This study shows that honokiol can induce a cell death distinct from apoptosis at lower concentrations. The death was characterized by cytoplasmic vacuolization with the endoplasmic reticulum swelling and accompanied by apoptosis at higher concentrations in NB4 and K562 cells. The two death processes may be in sequence at lower concentrations and in parallel with the increase of honokiol concentration. Membrane-associated cytotoxicity was involved in honokiol-induced paraptosis and apoptosis. Furthermore, honokiol inhibited concentration-dependent cell adhesion to extracellular matrix for NB4 cells. In addition, the cytotoxicity of honokiol combined treatment with imatinib was schedule- and concentration-dependent and the sequential administration of honokiol before imatinib appeared to be more beneficial in K562 cells. Taken together, the data suggest that honokiol induced a novel cell death pathway and there was cross-talk between apoptotic and non-apoptotic programmed cell death caused by honokiol in leukemia cells. Moreover, honikiol exhibited schedule-dependent synergy in combination with imatinib and sequential administration of imatinib followed by honokiol could be the optimal sequence to combine these two drugs in K562 cells.     

Preparation of honokiol-loaded chitosan microparticles via spray-drying method intended for pulmonary delivery

It has been demonstrated that spray-drying is a powerful method to prepare dry powders for pulmonary delivery. This paper prepared dispersible dry powders based on chitosan and mannitol containing honokiol nanoparticles as model drug. The results showed that the prepared microparticles are almost spherical and have appropriate aerodynamic properties for pulmonary delivery (aerodynamic diameters was between 2.8–3.3 μm and tapped density ranging from 0.14–0.?18?g/cm³). Moreover, surface morphology and aerodynamic properties of the powders were strongly affected by the content of mannitol. Fourier transform infra-red (FTIR) spectrum of powders indicated that the honokiol nanoparticles were successfully incorporated into microparticles. In vitro drug release profile was also observed. The content of mannitol in powders significantly influenced the release rate of honokiol from matrices.     

Anti-tumor effect of honokiol alone and in combination with other anti-cancer agents in breast cancer

Honokiol, an active component isolated and purified from Chinese traditional herb magnolia, was demonstrated to inhibit growth and induce apoptosis of different cancer cell lines such as human leukaemia, colon, and lung cancer cell lines; to attenuate the angiogenic activities of human endothelial cells in vitro; and to efficiently suppress the growth of angiosarcoma in nude mice. In this study, we have demonstrated that treatment of different human breast cancer cell lines with honokiol resulted in a time- and concentration-dependent growth inhibition in both estrogen receptor-positive and -negative breast cancer cell lines, as well as in drug-resistant breast cancer cell lines such as adriamycin-resistant and tamoxifen-resistant cell lines. The inhibition of growth was associated with a G1-phase cell cycle arrest and induction of caspase-dependent apoptosis. The effects of honokiol might be reversely related to the expression level of human epidermal growth receptor 2, (HER-2, also known as erbB2, c-erbB2) since knockdown of her-2 expression by siRNA significantly enhanced the sensitivity of the her-2 over-expressed BT-474 cells to the honokiol-induced apoptosis. Furthermore, inhibition of HER-2 signalling by specific human epidermal growth receptor 1/HER-2 (EGFR/HER-2) kinase inhibitor lapatinib synergistically enhanced the anti-cancer effects of honokiol in her-2 over-expressed breast cancer cells. Finally, we showed that honokiol was able to attenuate the PI3K/Akt/mTOR (Phosphoinositide 3-kinases/Akt/mammalian target of rapamycin) signalling by down-regulation of Akt phosphorylation and upregulation of PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) expression. Combination of honokiol with the mTOR inhibitor rapamycin presented synergistic effects on induction of apoptosis of breast cancer cells. In conclusion, honokiol, either alone or in combination with other therapeutics, could serve as a new, promising approach for breast cancer treatment.     

和厚朴酚神经保护作用的研究进展

和厚朴酚作为中药厚朴的主要活性成分之一,是一种多酚类化合物,具有抗炎、抗菌、抗肿瘤、抗氧化等多种作用.近年来发现,和厚朴酚对神经系统具有明显的保护作用.和厚朴酚易于通过血脑屏障,具有发展为广谱抗神经系统疾病药物的潜力.本文主要概述了目前和厚朴酚在神经保护方面的作用及机制,以期为后续的深入研究提供参考.     

Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats

The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 μg/kg/day from day 6–15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 μg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed–adverse-effect level (NOAEL) of honokiol microemulsion is 600 μg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 μg/kg/day, which is approximately 250 times above the therapeutic dosage.     

GC测定香砂平胃丸中苍术素、厚朴酚、和厚朴酚的含量

摘 要 目的： 建立香砂平胃丸中苍术素、厚朴酚、和厚朴酚的气相色谱含量测定方法。方法: ：采用HP-5毛细管柱（30 m×0.32 mm×0.25μm）,以氮气为载气,流速为2.0 ml·min^-1,进样口温度为300℃,检测器(FID)温度为300℃,进样量为1 μl,分流比为20∶1;采用程序升温模式,起始温度为100℃,保持7 min,以20℃·min^-1的速率升温至250℃,保持10 min。结果: 苍术素、厚朴酚、和厚朴酚分别在4.264～85.280 μg·ml^-1（r=0.999 7）、9.856～197.120 μg·ml^-1（r=0.999 5）、10.040～200.800 μg·ml^-1（r=0.999 6）范围内线性关系良好,平均回收率分别为98.2%、98.6%、99.3%,RSD分别为1.5%、1.5%、1.9%（n=6）。结论:该方法简便、准确、可靠,可用于香砂平胃丸的质量控制。     

和厚朴酚对组织因子途径抑制物 2诱导神经胶质瘤细胞凋亡的实验研究#br#

目的探讨和厚朴酚对组织因子途径抑制物 2（TFPI 2）表达的影响,以及和厚朴酚和TFPI 2过表达对人胶质瘤U251细胞凋亡的影响。 方法体外培养胶质瘤U87、U251、LN18、LN229、A172细胞系,荧光定量PCR（QPCR）检测不同细胞系中TFPI 2的表达。不同浓度（0、10、20、30、40和50 μmol／L）和厚朴酚干预U251细胞,QPCR和Western blotting检测TFPI 2 mRNA和蛋白的表达。采用腺病毒载体pGSadeno TFPI 2过表达U251细胞内TFPI 2的表达,流式细胞术及caspase 3试剂盒检测细胞凋亡率和caspase 3活性。 结果在选取的5种不同胶质瘤细胞株中,U251和A172细胞内TFPI 2 mRNA明显下降（P＜005）。和厚朴酚呈浓度依赖性增加U251细胞内TFPI 2 mRNA水平;其中50 μmol／L和厚朴酚干预24 h后, TFPI 2 mRNA表达水平升高最明显（P＜005）。腺病毒感染U251细胞后TFPI 2表达水平明显增加（P＜005）。过表达TFPI 2和50 μmol／L和厚朴酚干预均可增加U251细胞凋亡水平和caspase 3的活性（P＜005）。 结论和厚朴酚处理可增加U251细胞内TFPI 2的表达;和厚朴酚联合TFPI 2过表达显著诱导胶质瘤细胞凋亡。     

液相微萃取／后萃取-高效液相色谱法测定厚朴及其制剂中厚朴酚与和厚朴酚的含量

本文采用液相微萃取／后萃取（LPME／BE）与高效液相色谱联用法萃取并测定了中药厚朴及其制剂-藿香正气口服液和香砂养胃丸中厚朴酚与和厚朴酚的含量。优化了萃取效率影响因素，萃取溶剂、供相与接受相、转速及萃取时间。厚朴酚与和厚朴酚的线性范围分别为1．56—156μg/mL和1．10—110μg／mL；检测限（S／N=3）分别为0．10ug/mL和0.07μg/mL，回收率范围为98.3％-105．1％，RSD〈2．5％。