厚朴酚与和厚朴酚在大鼠体内的药代动力学

目的　观察厚朴酚与和厚朴酚在Wistar大鼠体内的动力学过程。方法　用实验建立的RP -HPLC法测定大鼠灌胃给予上述两种成分后不同时间各组织和体液中药物的含量及其蛋白结合率 ,并计算其在血中的药代动力学。结果　建立的方法能够良好分离两种成分 ,浓度 -色谱响应间线性相关系数均 >0 .999,平均加样回收率 >90 % ;两种成分在大鼠体内代谢符合一级消除动力学二室开放模型 ,Cmax　分别为 0 .974和 0 .5 2 2mg·L-1,T1/ 2 β　为 3.136和 3.2 84h ,T1/ 2ka　　为 0 .16 0和 0 .2 6 1h ;进入体内后 ,主要滞留于胃肠内 ,其他主要分布于肝、肺、肾组织中 ;血浆蛋白结合率分别为 6 8.5 4 %和 5 3.81% ;以粪排出为主 ,尿和胆汁排出量只有约 5 %。结论　厚朴酚与和厚朴酚吸收较差 ,进入循环后以肝代谢和肾排泄为主。     

HPLC法测定荣肝丸中栀子苷、橙皮苷、和厚朴酚、厚朴酚和丹参酮ⅡA的含量

目的：建立高效液相色谱法同时测定荣肝丸中栀子苷、橙皮苷、和厚朴酚、厚朴酚和丹参酮ⅡA 含量的方法。方法采用 Waters XTerra RP18色谱柱（4.6 mm ×250 mm,5μm）;流动相为乙腈-0.02％磷酸溶液,梯度洗脱;检测波长为238 nm;流速为1.0 mL·min -1;柱温40℃。结果栀子苷、橙皮苷、和厚朴酚、厚朴酚和丹参酮ⅡA分别在0.0274～0.8232、0.0559～1.6770、0.0083～0.2490、0.0243～0.7302、0.0026～0.0795μg 范围内线性关系良好,平均回收率分别为99.01％、98.95％、98.28％、100.93％和98.91％,RSD 分别为1.35％、1.54％、1.49％、2.08％和1.84％。结论本法简便、快速、结果准确、重复性好,可用于荣肝丸的质量控制。     

Co-delivery of honokiol,a constituent of Magnolia species,in a self-microemulsifying drug delivery system for improved oral transport of lipophilic sirolimus

Sirolimus is recognized as a P-glycoprotein (P-gp) substrate with poor water-solubility. To improve its solubility and bioabsorption, self-microemulsifying drug delivery systems (SMEDDS) containing a novel P-gp inhibitor, honokiol, were prepared. The aim of this work was to evaluate the enhanced transport of sirolimus SMEDDS as well as the roles of honokiol. In situ single-pass intestinal perfusion and in vitro human colon adenocarcinoma (Caco-2) cell models were applied to study the effects of honokiol within SMEDDS on the transport of sirolimus. The results indicated that a combination of honokiol with sirolimus in SMEDDS did not significantly alter the particle size, polydispersity index and release of drugs. In addition, the absorption rate constant (K_a) as well as the effective permeability coefficients (P_eff) of sirolimus in situ intestinal absorption, and the apparent permeability coefficients (P_app) of sirolimus in caco-2 cells were significantly enhanced by cremophor EL-based SMEDDS with honokiol as compared with those of SMEDDS without honokiol. Rhodamine123 uptake rate in caco-2 cells and in vitro cytotoxicity of sirolimus were enhanced by honokiol in SMEDDS indicating a substantial P-gp inhibition of honokiol. In conclusion, coadministration of honokiol with poor soluble P-gp substrate in SMEDDS, could serve as a favorable approach for oral delivery.     

香连理气丸的质量标准研究

目的建立香连理气丸的质量标准。方法采用显微鉴别处方中的厚朴、广藿香、甘草;采用薄层色谱法对黄连、木香和厚朴进行定性鉴别,采用高效液相色谱法测定香连理气丸中厚朴的含量。结果薄层色谱斑点清晰,专属性强;和厚朴酚在6.152~92.28μg/mL的范围内、厚朴酚在8.867~133.01μg/mL的范围内呈良好线性关系,香连理气丸中和厚朴酚平均回收率为98.95%（RSD=0.9%,n=9）,厚朴酚平均回收率为99.30%（RSD=1.2%,n=9）。结论本质量标准方法简单、操作简便、结果准确、重现性好,可用于香连理气丸的质量控制。     

和厚朴酚对结肠癌细胞生长影响及Caspase凋亡途径相关蛋白的表达研究

目的:探讨和厚朴酚对人结肠癌(SW480)细胞增殖抑制作用及诱导Caspase凋亡途径的研究.方法:利用MTT检测和厚朴酚在不同浓度和时问下对SW480细胞体外增殖的影响;用流式细胞术、Hoechst33258荧光染色检测及Caspase-3,-8,-9 酶活性检测方法和厚朴酚诱导下结肠癌SW480细胞凋亡指标及路径.结果:MTT结果显示和厚朴酚具明显抑制SW480细胞的体外增殖,其抑制率存在剂量和时间依赖性;药物处理24,48,72 h的IC50值分别是54.36、44.72、36.20 μmol/L.和厚朴酚作用细胞后,G0/G1期的细胞比例随药物浓度增加而逐渐增多(P<0.05),表明和厚朴酚能阻滞细胞于G0/G1期.荧光染料 Hoechst33258染色结果显示.细胞核出现典型的凋亡小体.Caspase家族蛋白酶活性检测结果,胞内Caspase-3,-8,-9酶家族分别被激活.其活性随不同时间点升高(P<0.05).结论:和厚朴酚能明显抑制人结肠癌SW480细胞体外增殖,并诱导大肠癌细胞SW480通过激活Caspase途径发生凋亡.     

和厚朴酚对人肝癌HepG2细胞增殖及NF-kB mRNA表达的影响

目的探讨和厚朴酚对体外培养的人肝癌细胞HepG2的增殖抑制作用及其对NF-kB基因mRNA水平的影响。方法采用MTT法检测和厚朴酚对HepG2细胞增殖的影响。以RT-PCR方法研究和厚朴酚对NF-kB基因mRNA表达的影响。结果和厚朴酚使人HepG2细胞增殖率明显下降,且呈剂量依赖效应;NF-kB基因mRNA水平随和厚朴酚浓度升高而降低。结论和厚朴酚对人HepG2细胞增殖有抑制作用,并能下调NF-kB的表达,从而起到抗肿瘤的治疗作用。     

分散液液微萃取-HPLC法测定藿香正气口服液中厚朴酚与和厚朴酚含量

建立基于离子液体的分散液液微萃取-HPLC法测定藿香正气口服液中厚朴酚与和厚朴酚含量的方法。厚朴酚与和厚朴酚分别在0.4～8μg.mL-1、0.3～6μg.mL-1的范围内,线性关系良好(r>0.9998)。本方法简便、灵敏,适用于中药制剂中厚朴酚与和厚朴酚含量测定。     

Specific oxidation of honokiol by Cunninghamella echinulata

Among 37 species of microbial strains, Cunninghamella echinulata AS 3.3400 were found to possess the ability to transform honokiol to (R)-magnolignan C (1) and (S)-magnolignan C (2) by regio-specific oxidation. Among them, 1 was a new compound. The structures of two compounds were determined by the analyses of CD, MS and NMR spectroscopic data.     

Honokiol inhibits H(2)O(2)-induced apoptosis in human lens epithelial cells via inhibition of the mitogen-activated protein kinase and Akt pathways

Oxidative stress-induced apoptosis in lens epithelial cells plays an important role in cataract formation, and its prevention may be of therapeutic interest. This study was performed to investigate the protective effect and mechanisms of honokiol on H₂O₂-induced apoptosis in human lens epithelial (HLE) cells. HLE cells (SRA01-04) were pretreated with honokiol at concentrations of 5 μM, 10 μM and 20 μM before 50 μM H₂O₂ treatment. The results demonstrated that pretreatment of honokiol inhibited the activation of caspase-3 and caspase-9 and downregulated the expression of Bcl-2. Mechanistically, honokiol suppressed H₂O₂-induced phosphorylation of ERK1/2, p38 mitogen-activated protein kinase (MAPK), JNK and Akt. Honokiol also inhibited H₂O₂-induced nuclear factor-κB (NF-κB)/p65 phosphorylation and translocation in HLE cells. These results demonstrate that honokiol suppresses H₂O₂-induced HLE cell apoptosis via interference with the MAPKs, Akt and NF-κB signaling, suggesting that honokiol might have a potential effect against cataract formation.