蛇床子素-pH敏感性纳米粒的制备及其在大鼠体内的药代动力学

目的:制备蛇床子素-Eudragit S100纳米粒(Ost-S100-NP)及其冻干制剂(Fd-Ost-S100-NP),并考察相关特性;考察蛇床子素、纳米粒制剂和冻干制剂在大鼠体内的药代动力学及相对生物利用度。方法:以乳化-溶剂扩散法联合冷冻干燥技术制备Ost-S100-NP胶体溶液及其冻干粉末;动态透析法研究其体外释药动力学;以HPLC测定大鼠灌胃后血浆中的Ost浓度,3P97程序计算药代动力学参数。结果:Ost-S100-NP和Fd-Ost-S100-NP的平均粒径分别为(55.4±2.1)和(87.7±2.3)nm;包封率>95%;电镜下呈均匀规则的圆球形;且纳米粒制剂在pH>6.0的释放介质中释药速率明显增大,具有显著pH敏感性;药物在大鼠体内药代动力学均符合二室模型,Ost-S100-NP和Fd-Ost-S100-NP的相对生物利用度分别为原料药的161.1%和118.4%。结论:以pH敏感性材料Eudragit S100为载体有望开发成一种高效、低毒的蛇床子素纳米制剂。     

参麦注射液的抗肿瘤作用研究

目的 研究参麦注射液体内外抗肿瘤作用.方法 以小鼠肉瘤S180、肝癌H22、Lewis肺癌实体瘤模型考察参麦注射液的体内抑瘤作用;通过MTT法考察参麦注射液体外对人宫颈癌HeLa细胞和人肝癌HepG 2细胞的增殖抑制作用.结果 参麦注射液在体内对小鼠肉瘤S180、肝癌H22、Lewis肺癌均有显著的抑制作用,且呈剂量相关性,中、高剂量抑瘤率可达35％以上;体外对人宫颈癌HeLa细胞和人肝癌HepG 2细胞亦有增殖抑制作用,且呈浓度-时间相关性,48 h的IC50值分别为0.36、0.72 g/mL,72h的IC50值分别为0.21、0.29 g/mL.结论 参麦注射液体内外均有显著的抗肿瘤活性.     

艾迪粉针剂的抗肿瘤作用

目的通过体内外抗肿瘤实验观察艾迪粉针剂的抗肿瘤作用。方法抗肿瘤体内实验:建立小鼠移植性肉瘤S180和小鼠肝癌H22的实体瘤模型,艾迪粉针剂对小鼠尾静脉给药,连续处理7 d,第8天剥离瘤块称质量,计算抑瘤率,与化疗药合并用药考察减毒增效作用;建立小鼠L1210白血病模型,阳性对照组为顺铂,考察生命延长率。体外实验:常规传代培养人肝癌BEL7402、人宫颈癌HeLa细胞、人黑色素瘤A375 S2细胞、人胃癌SGC 7901和小鼠纤维肉瘤L929细胞,用MTT法检测活细胞数和生长抑制率。结果艾迪粉针剂连续7 d每日1次静脉注射对小鼠肉瘤S180和小鼠肝癌H22具有明显的抑瘤作用,本品与化疗药合并用药有增效作用;艾迪粉针剂体外对多种人肿瘤细胞具有体外抗肿瘤活性,且具有较低的IC50值。结论艾迪粉针剂具有体内和体外抗肿瘤活性。     

新型雌激素化合物17aα-D-高炔雌二醇-3-乙酯抗肿瘤活性的初步研究

目的对新型雌激素化合物17aα-D-高炔雌二醇-3-乙酯进行体外和体内的抗肿瘤活性实验研究。方法采用MTT法进行药物体外对肺腺癌细胞A549和人肝癌细胞Bel-7402抗肿瘤实验,测定IC50;体内对小鼠肺腺癌LA795抑制作用采用常规抗肿瘤实验方法进行,腹腔给药观察抑瘤率,胸腺及脾重量、指数的变化。结果17aα-D-高炔雌二醇-3-乙酯体外肺腺癌细胞A549和人肝癌细胞Bel-7402的IC50分别为12.28μg·mL-1、17.79μg·mL-1;体内对小鼠肺腺癌LA795实体瘤最佳抑制率达60.0%,各给药组与空白对照组比较有非常显著性差异(P<0.01);脏器重量及指数与空白对照组比较无显著差异,而与阳性对照药环磷酰胺(CY)组存在显著性差异(P<0.01)。结论17aα-D-高炔雌二醇-3-乙酯体外和体内对实验肿瘤均有明显的抗肿瘤活性,而且在给药剂量下对实验动物未表现出任何毒性反应,值得深入研究。     

马甲子叶提取物的抗肿瘤活性研究

目的 研究马甲子叶提取物的体内外抗肿瘤活性.方法 采用系统溶剂萃取法萃取马甲子叶醇提物,采用MTT法分别检测马甲子叶水提物、醇提物、石油醚部位、乙酸乙酯部位和正丁醇部位对人肝癌HepG-2、人胃癌MGC-803、人宫颈癌Hela细胞的体外抗肿瘤活性;考察马甲子叶乙酸乙酯部位对S180荷瘤小鼠的体内抗肿瘤活性.结果 马甲子乙酸乙酯部位对3种肿瘤细胞均有明显抑制作用,呈一定量效关系,IC50分别为23.68、24.91、75.32 μg·mL-;乙醇提取物和石油醚部位对3种肿瘤细胞均有一定抑制作用;正丁醇部位和水提物的抑制作用不明显.乙酸乙酯部位对S180荷瘤小鼠的体内抗肿瘤作用明显,中剂量的抑瘤效果与环磷酰胺的相当,抑瘤率达49.38％.结论 马甲子叶乙酸乙酯部位的抗肿瘤活性最强.     

空间立构pH敏感喜树碱新型纳米胶束制备及评价#br#

目的 制备空间立构pH敏感喜树碱新型纳米胶束,对其进行质量评价,并考察了胶束的体外抗肿瘤活性。方法 采用透析法制备载喜树碱纳米胶束,响应面法优化其处方工艺,分别用扫描电子显微镜和动态激光散射仪表征其形貌、粒径及粒度分布,采用透析法测定其体外释放行为,并通过细胞活力试验考察其体外抗肿瘤活性。结果 优化得到载药胶束最佳处方工艺为：喜树碱与载体的质量比为26.5:100,搅拌时间为15.5h,透析时间为8h。载药胶束呈球状,粒径(170.4±28.49)nm,PDI为0.236;包封率78.31%,载药量23.55%;体外释放兼具缓释和pH敏感性双重效果。载药胶束和CPT对于Hela细胞的IC50值分别为1.75和4.64μg/mL,而两者对于MCF-7细胞的IC50值分别为5.41和12.78μg/mL。结论 成功制备得到一种新型空间立构pH敏感喜树碱纳米胶束,提高了喜树碱的水溶性及稳定性,并且该胶束具有良好的体外肿瘤抑制效果。     

鸡血藤提取物的抗肿瘤作用研究

目的：研究鸡血藤提取物的体内与体外抗肿瘤作用。方法：采用mT法检测鸡血藤提取物对体外培养的5种肿瘤细胞增殖的抑制作用;体内试验采用小鼠实体瘤S180细胞株接种小鼠,建立实体瘤与腹水瘤模型。计算抑瘤率与生命延长率。结果：鸡血藤提取物在5μg／ml-80μg/ml剂量的范围内对5种肿瘤细胞均有抑制作用。体内试验小鼠分另吐灌胃给予20mg/kg、50mg／kg、100mg／kg,能抑制小鼠体内肿瘤增长。也能明显提高腹水瘤小鼠的生命延长率。结论：鸡血藤提取物在体外对不同组织来源的肿瘤细胞增殖有明显的抑制作用;在体内能抑制小鼠体内瘤体生长,明显延长小鼠的生存期。     

天龙核苷体外抗肿瘤作用的研究

目的探讨天龙核苷的体外抗肿瘤作用。方法分别选用K562和A549细胞株,采用光镜检查细胞形态学变化,MTT法测定天龙核苷对两种细胞的体外抑制作用。结果光镜显示给药组细胞变圆变小,折光性下降,出现发泡现象,染色质浓缩致密并分裂成块,多数细胞形成凋亡小体;MTT实验结果表明,对核苷敏感的最低药物浓度分别为100μg/mL和50μg/mL,IC50分别为277μg/mL和298μg/mL。结论天龙核苷有一定的体外抑瘤作用,并有较好量效关系。     

熊果酸的抗肿瘤作用

目的 研究熊果酸的抗肿瘤活性.方法 体外用MTT比色法测定熊果酸对肿瘤细胞HepG2和S180的增殖抑制作用,再用DNA凝胶电泳法测定熊果酸对HepG2细胞凋亡的诱导作用;体内采用小鼠实体瘤模型,观察熊果酸对HepG2和S180实体瘤的抑制作用.结果 熊果酸对HepG2和S180的增殖有良好的抑制作用,48h内对细胞半数生长的抑制剂量(IC50)分别为12.5μg/ml和13.9μg/ml.同时熊果酸能够诱导HepG2发生凋亡.20.0μg/ml熊果酸对HepG2和S180实体瘤抑制率分别达到52.98%和44.41%.结论 熊果酸通过抑制增殖和诱导凋亡对肿瘤细胞株HepG2和S180表现出良好的抗肿瘤活性.     

香菇多糖的抗肿瘤活性研究

目的:研究香菇多糖(EGb)的体内、体外抗肿瘤活性。方法:选取人乳腺癌细胞MCF-7、肝癌细胞HepG2、胃癌细胞SW480,不同浓度的香菇多糖分别处理3种肿瘤细胞,MTT法分别检测香菇多糖的体外抗肿瘤活性;选取荷MCF-7肿瘤裸鼠,给予香菇多糖,通过肿瘤生长抑制率,考察香菇多糖的体内抗肿瘤活性。结果:香菇多糖对3种肿瘤细胞均有细胞毒性,呈剂量依赖性,IC50分别为6.855、10.083、8.563μM;香菇多糖可显著降低肿瘤重量,提高肿瘤生长抑制率。结论:香菇多糖体内外实验均显示良好抗肿瘤活性。     

舒尼替尼衍生物ZH26体内外抗肿瘤作用

目的研究舒尼替尼衍生物ZH26的抗肿瘤作用。方法采用甲基噻唑比色法体外检测ZH26对多种肿瘤细胞株的生长抑制作用;建立S180肉瘤、Colon26结肠癌小鼠肿瘤模型和裸鼠人体肿瘤移植瘤NCI-H460人大细胞肺癌移植瘤、SPC-1肺腺癌移植瘤模型,评价ZH26的体内抗肿瘤活性。结果 ZH26体外对多株肿瘤细胞株有较好的抑制作用,对大多数肿瘤细胞株的IC50值为3.33～5.68μg/mL,与舒尼替尼相当。体内试验表明,30～90 mg/kg ZH26对小鼠S180肉瘤的抑瘤率为40.55%～66.82%;对小鼠Colon26结肠癌的抑瘤率为55.41%～78.14%;对NCI-H460人大细胞肺癌的抑瘤率为48.14%～70.56%;对SPC-1肺腺癌的抑瘤率为42.06%～92.18%。结论 ZH26具有良好的体内外抗肿瘤作用,相关机制尚待进一步研究。     

Effects of silver nanoparticles on rat hepatic cytochrome P450 enzyme activity

Silver nanoparticles (AgNPs) are increasingly used in various products and consequentially the potential adverse effects associated with exposure to them are of concern. This study investigated the effects of AgNPs on the hepatic drug-metabolizing enzymes of the cytochrome P450 (CYP) families 1, 2 and 3, using both in vitro and in vivo biological assays. AgNPs were orally administered to Sprague-Dawley rats at various concentrations (0-1000 mg/kg body weight/day) for 2 weeks. No effect was found on the plasma levels of ALT, AST and ALP in all treated rat groups, and no significant change in the activities of CYP1A, CYP2C, CYP2D, CYP2E1 and CYP3A was observed for all tested AgNP doses. The results correlated with the observation that no AgNPs were detected in the liver sections of the tested rats. However, the in vitro system using rat liver microsomes demonstrated a strong inhibition of CYP2C (IC(50)?= 28 μg/mL) and CYP2D (IC(50)?= 23 μg/mL) activities, but not of CYP1A, CYP2E1 and CYP3A activities (IC(50) > 100 μg/mL) at concentrations up to 100 μg/mL of AgNPs. The inhibitory effect of AgNPs on these CYPs indicates the possibility of the AgNP-drug interaction when co-administered with some medicines and this may cause adverse effects to patients.     

薯蓣皂苷元衍生物的抗肿瘤活性研究

目的研究薯蓣皂苷元衍生物在体外的抗肿瘤活性。方法采用MTT法对人恶性黑色素瘤细胞A375、人肺腺癌细胞A549、人肝癌细胞HepG-2及人慢性髓原白血病细胞株K562进行体外抗肿瘤活性试验。结果薯蓣皂苷元衍生物对4个肿瘤细胞株A375、A549、K562、HepG-2具有不同程度的抗肿瘤活性。结论绝大部分薯蓣皂苷元衍生物对4个肿瘤细胞株有较好的抗肿瘤活性,IC50值都低于30μmol.L-1。化合物22对细胞株A375的IC50=4.48μmol.L-1,化合物9、10对细胞株K562的IC50分别为2.51、2.38μmol.L-1;显示其抗肿瘤活性与对照化合物1-(3β-薯蓣皂苷元)-3-苄基咪唑溴盐相当。     

Anticancer activity of sodium caffeate and its mechanism

AIM: To study the anticancer activity of sodium caffeate (SC). METHODS: A nucleoside transport assay was used to analyze the inhibitory effects of SC on nucleoside rescue. The MTT assay was used to measure cell proliferation. Flow cytometry was used to measure the apoptosis of BEC-7402 induced by SC and the cell cycle distribution change. Western blotting analysis was employed to investigate Bcl-2, caspase and Bax expression. Intracellular Ca2+ and mitochondrial membrane potential were determined by flow cytometry. In vivo anti-tumor activity was measured using a tumor transplantation model in mice. RESULTS: SC inhibited the nucleoside transport of BEL-7402 cells with an IC(50) of 1.02 microg/mL. SC inhibited tumor cell proliferation with an IC50 between 100 microg/mL and 200 microg/mL. SC induced BEL-7402 cell apoptosis in a time- and dose-dependent manner, which was induced by arresting cells in S phase. The in vivo study showed that tumor growth was inhibited in a dose-dependent manner. Activated caspase-3 and Bax expression were up-regulated after treatment with SC, while Bcl-2 expression was down-regulated. Intracellular Ca2+ was increased while mitochondrial membrane potential was decreased by SC. CONCLUSION: SC is a new anticancer agent with promising potential.     

In vitro studies to assess the antidiabetic, antiperoxidative, and radical scavenging potential of Stereospermum colais

Context: Stereospermum colais (Buch.-Ham. ex Dillw.) Mabberley (Bignoniaceae), which has traditional medicinal properties, is distributed all over deciduous forests. In spite of its many uses, the antidiabetic, antiperoxidative and radical scavenging activities of this species have not been assessed, and its chemical composition is scarcely known. Objective: Antidiabetic, antiperoxidation, xanthine oxidase (XO) inhibition, and radical scavenging activities of acetone and methanol extracts of Stereospermum colais roots were investigated. Protective effects of Stereospermum colais root extract in stabilizing sunflower oil was also examined. Materials and methods: The protective effect of acetone (ASC) and methanol (MSC) extracts of Stereospermum colais root for the potential inhibition of α-glucosidase and α-amylase enzymes were studied by in vitro method. Glycation inhibitory activity was also studied to inhibit the production of glycated end products. Results: Compared with acarbose, ASC showed a strong inhibitory activity against α-glucosidase (IC(50) 61.21 μg/mL) and a moderate inhibitory activity against α-amylase (IC(50) 681.08 μg/mL). Glycation inhibitory activity of Stereospermum colais root extracts by using an in vitro glucose-bovine serum albumin (BSA) assay was also done and compared with standard gallic acid. ASC also shows high XO inhibition potential, free radical scavenging activities, and low p-anisidine value indicates the high medicinal potency of Stereospermum colais root. Discussion and conclusion: These results suggest that the extract of Stereospermum colais may be interesting for incorporation in pharmaceutical preparations for human health, since it can suppress hyperglycaemia, and or as food additives due to its antiradical efficiency.     

芦荟多糖影响肿瘤血管生成作用的初步研究

目的研究芦荟多糖（AP）抑制肿瘤新生血管生成的作用。方法以细胞生长抑制率和IC50为考察指标,通过MTT法,测定AP对人脐静脉内皮细胞（ECV304）生长的抑制作用,并观察量效和时效之间的作用关系。结果各实验组表现肿瘤生长明显受到抑制,AP对ECV304细胞生长的抑制作用呈浓度和时间的依赖性。在24、48、72 h时间段测得的IC50分别为1.1120、0.3260、0.0795μg/mL。结论 AP具有明显的抗肿瘤新生血管生成作用,并呈浓度和时间上的依赖性。     

相思子蛋白P2抗肝癌作用及对端粒酶活性影响

目的研究相思子蛋白P2对肝癌细胞生长的抑制作用及机制。方法体外实验:MTT法检测相思子蛋白P2对人肝癌HepG2细胞增殖的抑制作用。流式细胞仪检测对HepG2细胞周期和细胞凋亡的影响。TRAP-SYBR-Green染色法检测相思子蛋白P2作用前后细胞端粒酶活性的改变。体内实验:相思子蛋白P2 50、75、100μg.kg-1连续灌胃给药10 d,观察对小鼠肝癌H22移植性肿瘤的生长抑制作用。小鼠口服给药急性毒性观察。结果相思子蛋白P2可明显抑制HepG2细胞增殖,IC50值为5.172×10-3 mg.L-1。在5×10-5～1×10-3 mg.L-1剂量作用下,可引起HepG2细胞凋亡。相思子蛋白P2主要将细胞周期滞留在S期,从而抑制了肿瘤细胞增殖。同时可使细胞端粒酶活性明显降低,其下调端粒酶活性的作用随药物浓度的增加而明显增强。相思子蛋白P2对小鼠H22肝癌细胞生长有明显抑制作用,100μg.kg-1抑瘤率达62.47%,且对胸腺和脾脏指数的影响较环磷酰胺小。小鼠口服给药LD50值为6.77 mg.kg-1。结论相思子蛋白P2体内外均可明显抑制肝癌细胞的生长,其抗肿瘤作用可能与下调细胞端粒酶活性、改变细胞周期分布,诱导细胞凋亡有关。     

藤茶总黄酮体外抗人肝癌细胞作用研究

目的:研究藤茶总黄酮体外抗人肝癌细胞的作用。方法:以MTT法、细胞生长曲线法、集落形成法观察藤茶提取物对人肝癌BEL7404细胞的体外抑制作用。结果:藤茶总黄酮能显著抑制体外培养的BEL7404细胞的生长。MTT法测得的半数抑制浓度(IC50)为28·59μg·mL-1;细胞生长曲线法提示藤茶总黄酮对BEL7404细胞的生长有显著的抑制作用;集落形成法提示当药物浓度在22·22μg·mL-1以上时IC50为100%,当药物浓度在14·81μg·mL-1时IC50为58·05%。结论:藤茶总黄酮对体外培养的BEL7404细胞有显著的抑制作用。