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61.
Xiaoying Wang Dandan Xiao Cui Ma Lixin Zhang Qingya Duan Xiaodong Zheng Min Mao Daling Zhu Qian Li 《Journal of pharmacological sciences》2019,139(3):158-165
Abnormal autophagy plays critical roles in the structure and function of the pulmonary vasculature. Cyclophilin A (CyPA) can be secreted from cells in response to hypoxia and oxidative stress, which are involved in inducing autophagy and regulating the function of endothelial cells in pulmonary arterial hypertension. Honokiol is a small molecule natural compound; it has many bioactivities, such as antitumor, anti-inflammatory, antioxidant and antiangiogenic properties, but how honokiol mediates autophagy in pulmonary arterial hypertension is unclear. Rat' lungs gavaged with honokiol were examined for autophagy via western blot and fluorescence microscopy. In addition, western blot, quantitative RT-PCR and immunofluorescence were employed to test the expression of CyPA and autophagy markers in pulmonary artery endothelial cells (PAECs). Small interfering RNA targeting CyPA (si-CyPA) was used to knockdown the expression of CyPA, and then autophagy was tested with mRFP-GFP-LC3 fluorescence microscopy and western blot. We found that honokiol could reduce the expression of CyPA and autophagy markers in vivo and in vitro. Furthermore, autophagy was also down-regulated by si-CyPA. Taken together, we revealed a novel mechanism by which honokiol regulates autophagy. The results revealed that honokiol can alleviate autophagy and pulmonary arterial hypertension regulated by CyPA in PAECs. 相似文献
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目的:建立厚术胶囊的质量标准。方法:采用薄层色谱(TLC)法对方中苍术、三七、白芍和山楂药材进行定性鉴别;采用高效液相色谱法测定厚朴中厚朴酚、和厚朴酚的含量。结果:TLC斑点清晰,阴性对照无干扰。厚朴酚与和厚朴酚的进样量分别在0.080~0.400μg(r=0.9999)、0.048~0.240μg(r=0.9999)范围内与各自峰面积积分值呈良好的线性关系;平均回收率分别为98.42%、98.34%,RSD分别为0.63%、0.90%(n=6)。结论:所建标准可有效控制厚术胶囊的质量。 相似文献
64.
厚朴酚与和厚朴酚在大鼠体内的药代动力学 总被引:10,自引:0,他引:10
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。 相似文献
65.
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。 相似文献
66.
Weiming Ding Xucheng Hou Shuangchen Cong Yuanyuan Zhang Mengmeng Chen Jiongxi Lei 《Drug delivery》2016,23(7):2513-2523
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 (Ka) as well as the effective permeability coefficients (Peff) of sirolimus in situ intestinal absorption, and the apparent permeability coefficients (Papp) 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. 相似文献
67.
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. 相似文献
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69.
Zhaohua Wang Dewu Zhang Zhengshun Wen Lin Yang Yeling Wang Shanjun Wei Jungui Dai 《中国药学》2013,22(6):531
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. 相似文献
70.
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. 相似文献