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1.
陈艳  张梅  王金萍  杨锋 《药学实践杂志》2017,35(4):334-336,370
目的 测试辣木叶和种子的急性毒性以及安全剂量范围。方法 参照《中药药理研究方法学》设计实验,确定中药新药的最大耐受量和急性毒性。结果 小鼠对辣木叶超微粉和辣木叶醇提物的最大耐受量分别为0.4 g/20 g、0.8 g/20 g,辣木叶超微粉和辣木叶醇提物的成人日剂量分别在10 g/50 kg、20 g/50 kg以下为安全剂量。结论 辣木叶为较安全的药食两用植物,其药理作用值得进一步研究。  相似文献   

2.
目的 观察辣木叶及其复方对便秘模型大鼠的通便作用和相关胃肠激素水平的影响。方法 按体质量随机将100只SD大鼠分为10组,即对照组、模型组、番泻叶浸液组(阳性对照,0.01 g/kg)和辣木叶水提液低、中、高剂量(0.79、1.58、3.15 g/kg)组,黄芪白术(1.05 g/kg)组,辣木叶复方水提液低、中、高剂量(1.84、2.63、4.20 g/kg)组。除对照组外,均采用盐酸洛哌丁胺(6.67 mg/kg)复制便秘模型,每日2次,连续2周。造模结束后,各给药组分别ig相应受试样品,每天1次,连续7 d。记录各组大鼠体质量、最后24 h粪便粒数,测定粪便含水量、小肠炭末推进率,ELISA试剂盒法检测血清P物质、生长抑素含量及结肠胃动素、血管活性肠肽含量。结果 与模型组比较,辣木叶水提液中、高剂量组及辣木叶复方水提液各剂量组的体质量增量显著升高(P<0.05);各给药组大鼠的排便粒数与模型组比较均显著性增加(P<0.05);各给药组大鼠粪便含水量与模型组比较均无显著性差异;辣木叶水提液中、高剂量组及其复方水提液中、高剂量组小肠炭末推进率显著增加(P<0.05、0.01)。辣木叶水提液中、高剂量组及其复方水提液各剂量组血清P物质含量、结肠组织胃动素含量均显著高于模型组(P<0.05、0.01);辣木叶水提液高剂量组及辣木叶复方水提液中、高剂量组大鼠血管活性肠肽含量较模型组降低显著(P<0.05、0.01);各给药组大鼠血清生长抑素水平均显著低于模型组(P<0.01)。辣木叶复方水提物上述作用均好于等剂量辣木叶水提液及黄芪白术水提液。结论 辣木叶及其复方具有良好的通便作用,可能与调节胃肠激素水平有关;复方的通便及调节胃肠激素的作用优于单味药辣木叶及黄芪白术,体现出复方配伍的整体优越性,其中辣木叶侧重调节P物质、胃动素及血管活性肠肽水平,而黄芪白术主要调节生长抑素水平。  相似文献   

3.
目的观察辣木果实对链尿佐菌素诱导大鼠糖尿病血糖和周围神经病变的改善作用,并探讨其作用机制。方法采用链脲佐菌素诱发糖尿病大鼠模型。将糖尿病大鼠随机分为模型组、二甲双胍组和辣木果实7.80、15.61、31.22 g/kg组,每组各10只。另取正常大鼠10只,作为对照组。模型组和对照组ig同体积的纯净水,二甲双胍组给予盐酸二甲双胍片0.2 g/kg。所有大鼠给药体积均为20 mL/kg,连续给药8周。观察药物对糖尿病大鼠空腹血糖、糖化血清蛋白、糖耐量、血中红细胞山梨醇水平、坐骨神经山梨醇水平以及坐骨神经组织形态学的影响。结果与模型组比较,辣木果实15.61、31.22 g/kg组均能明显降低糖尿病大鼠各时间点血糖曲线下面积(P0.01)。治疗8周后,辣木果实15.61、31.22 g/kg组红细胞山梨醇水平明显低于模型组(P0.01);辣木果实7.80、15.61、31.22 g/kg量组坐骨神经山梨醇水平明显低于模型组(P0.01)。治疗8周后,辣木果实15.61、31.22 g/kg组糖化血清蛋白水平明显低于模型组(P0.05、0.01)。辣木果实组坐骨神经病理形态学病变有不同程度减轻,其中辣木果实15.61 g/kg组基本恢复正常,神经纤维排列紧密。辣木果实31.22 g/kg组改善情况弱于辣木果实15.61 g/kg组。结论辣木果实对糖尿病大鼠周围神经病变具有明显的改善作用,其作用机制可能与体内山梨醇代谢异常的改善有关。  相似文献   

4.
目的:考察精氨酸复溶的多西他赛胶束的体外药效及体内分布情况。方法:用CCK-8法考察多西他赛胶束和多西他赛注射液对肿瘤细胞的增殖抑制作用。以荧光染料DIR标记多西他赛聚合物胶束,通过活体成像系统比较精氨酸水溶液复溶组,生理盐水复溶组和多西他赛注射液组的荧光分布。结果:多西他赛胶束组IC50值明显比多西他赛注射液组高。精氨酸复溶的多西他赛胶束组肿瘤部位荧光强度比生理盐水复溶组和多西他赛注射液组都强。结论:精氨酸复溶的多西他赛胶束肿瘤靶向性更强且在肿瘤部位的停留时间更长,但其体外抗肿瘤活性有待提高。  相似文献   

5.
目的 探讨辣木叶水提物(MOLAE)对脂肪堆积人HepG2细胞的调节作用。方法 制备MOLAE冻干粉;通过CCK-8法检测油酸钠-钠棕榈酸酯(O-P)对HepG2细胞活力的影响、油红O染色检测O-P对细胞脂质堆积的影响、试剂盒法检测O-P对细胞三酰甘油(TG)、总胆固醇(TC)水平的影响,筛选O-P诱导HepG2细胞脂质代谢异常模型的作用浓度及时间;CCK-8法检测辛伐他汀、MOLAE对HepG2细胞活力的影响,筛选安全作用浓度;设立对照组、模型组、辛伐他汀(阳性药,15 μmol·L-1)组和MOLAE(3.125、6.250、12.500、25.000、50.000 μg·mL-1)组,除对照组外,其他各组均给予0.4-0.2 mmol·L-1的O-P诱导细胞脂质沉积,诱导3 h后开始给药,干预24 h后,CCK-8法检测细胞活性,油红O染色观察细胞中脂滴形成情况,试剂盒法测定细胞中TG、TC、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)及丙二醛(MDA)水平。结果 确定造模方式为:0.4-0.2 mmol·L-1的O-P作用HepG2细胞3 h后开始给药;10、15 μmol·L-1的辛伐他汀和3.125~100.000 μg·mL-1的MOLAE作用于HepG2细胞24、48 h后,不影响细胞活力。与模型组比较,不同浓度的MOLAE(3.125、6.250、12.500、25.000、50.000 μg·mL-1)均能降低TG、TC、MDA水平(P<0.05、0.01),显著升高GSH、SOD水平(P<0.05、0.01)。油红O染色结果表明,辛伐他汀组和MOLAE组(12.5、25.0 μg·mL-1)脂滴堆积现象均较模型组有明显改善。结论 MOLAE能够降低O-P诱导的HepG2细胞中TG、TC水平,提高GSH、SOD水平和降低MDA水平,减少细胞中脂质堆积的现象。  相似文献   

6.
Antrodia camphorata (A. camphorata) has been shown to induce apoptosis in cultured human breast cancer cells (MDA-MB-231). In this study, we report the effectiveness of the fermented culture broth of A. camphorata in terms of tumor regression as determined using both in vitro cell culture and in vivo athymic nude mice models of breast cancer. We found that the A. camphorata treatment decreased the proliferation of MDA-MB-231 cells by arresting progression through the G1 phase of the cell cycle. This cell cycle blockade was associated with reductions in cyclin D1, cyclin E, CDK4, cyclin A, and proliferating cell nuclear antigen (PCNA), and increased CDK inhibitor p27/KIP and p21/WAF1 in a dose and time-dependent manner. Furthermore, the A. camphorata treatment was effective in delaying tumor incidence in the nude mice inoculated with MDA-MB-231 cells as well as reducing the tumor burden when compared to controls. A. camphorata treatment also inhibited proliferation (cyclin D1 and PCNA) and induced apoptosis (Bcl-2 and TUNEL) when the tumor tissue sections were examined histologically and immunohistochemically. These results suggest that the A. camphorata treatment induced cell cycle arrest and apoptosis of human breast cancer cells both in vitro and in vivo.  相似文献   

7.
目的 评价水飞蓟素磷脂复合物微孔渗透泵(SM-PC MPOP)控释片的体外释药特性、比格犬体内药动学及其体内外相关性。方法 释放介质为pH7.5的磷酸盐缓冲液(添加0.5%十二烷基硫酸钠),以高效液相色谱法(HPLC)检测SM-PC MPOP的体外释放特征。用6只比格犬进行双周期交叉对照实验,按照30 mg/kg的剂量给药。HPLC法测定比格犬血浆内水飞蓟素的主要成分水飞蓟宾的质量浓度,应用药动学软件进行数据分析。结果 SM-PC MPOP在12 h累积释放度超过85%。药动学研究情况表明,受试制剂(SM-PC MPOP)和参比制剂(市售水飞蓟素胶囊)在比格犬体内的主要药动学参数:Tmax分别为(3.2±0.4)、(0.9±0.1)h,Cmax分别为(0.298 6±0.068 9)、(0.629 9±0.076 5)μg/ml,AUC0→24分别为(2.996 8±0.583 3)、(2.268 9±0.432 8) h·μg/ml,SM-PC-MPOP对市售水飞蓟素胶囊的相对生物利用度为(162.21±30.82)%...  相似文献   

8.
番茄红素微囊的体内外药剂学行为   总被引:5,自引:1,他引:5  
目的考察番茄红素微囊的体外释放、番茄红素原料及番茄红素微囊在家犬体内的药代动力学、体外释放和体内吸收的相关性。方法用分光光度法测定释放介质中番茄红素的含量。用HPLC法测定家犬体内的番茄红素含量,数据用3P87程序处理,得到各主要药代动力学参数。体内吸收与体外释放进行点点相关。结果微囊体外释放呈肠溶性,原料及番茄红素微囊的T1/2α分别为7.30和15.06 h;T1/2β分别为28.10和46.76 h;Tmax分别为22.32和41.03 h;AUC0-∞分别为1.67和2.08 μg·h·L-1。体内外相关性良好。结论微囊较原料药呈现缓释特征,体内外相关性结果表明可以根据体外释放情况预测体内的吸收。  相似文献   

9.
Methanol extract of Symplocos cochinchinensis S. Moore leaves was evaluated for its in vitro and in vivo antioxidant activity. The total phenolic content of the extract was 230 mg of gallic acid equivalents/g extract. The extract showed very good scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) (IC50 620.30 ± 0.14 μg/ml), hydroxyl (IC50 730.21 ± 1.05 μg/ml), nitric oxide (IC50 870.31 ± 0.19 μg/ml) radicals, as well as high reducing power. The extract also showed strong suppressive effect on lipid peroxidation. In in vivo study CCl4 induced oxidative stress produced significant increase in SGOT, SGPT and LDH levels along with reduction in liver SOD, CAT, GSH and GPx levels. Pre-treatment of rats with the extract (250 and 500 mg/kg) for 7 days showed significant reduction in the levels of SGOT, SGPT and LDH compared to CCl4 treated rats. SOD, CAT, GSH and GPx levels were increased significantly due to treatment with the extract. The activity of the extract was comparable to the standard drug, silymarin (25 mg/kg). The results suggest that the leaves of S. cochinchinensis are a source of natural antioxidants.  相似文献   

10.
Gymnema montanum is widely used in ancient medicine for the ailment of various diseases. Oral administration of 200 mg kg(-1) (body weight) BW of the alcoholic extract of the leaf for 3 weeks resulted in a significant reduction in blood glucose and an increase in plasma insulin, whereas the effect of 50 and 100 mg kg(-1) BW was not significant. The alcoholic extract also resulted in decreased free radical formation in plasma of diabetic rats. Thus, this study shows that Gymnema montanum leaf extract (GLEt) possess antihyperglycemic and antiperoxidative effect. The decrease in lipid peroxides and increase in reduced glutathione (GSH), ascorbic acid (Vitamin C) and alpha-tocopherol (Vitamin E) clearly show the antioxidant properties of GLEt. The effect of GLEt was most prominently seen in the case of animals given 200 mg kg(-1) BW. In addition, the results suggest that GLEt was highly effective than the reference drug glibenclamide.  相似文献   

11.
The antioxidant properties of different extracts of Halenia elliptica was investigated by employing various established in vitro systems. The results showed that various extracts possessed strong antioxidant activity in vitro, and the 70% methanol extract (ME) had the strongest antioxidant activity. Based on our in vitro results, ME was used for investigating the antioxidant properties of H. ellipticain vivo. The liver and kidney of CCl4-intoxicated animals exhibited a significant decrease in superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels. Additionally, these organs exhibited a significant increase in the level of malondialdehyde (MDA). These changes were significantly reversed, in a dose-dependent manner, after treatment with ME and the standard treatment Vitamin E. Thus, it may be concluded that the ME possesses potent antioxidant properties, and might be valuable natural source of antioxidants that could be applicable to both the medical and food industries.  相似文献   

12.
目的 研究木兰花碱在大鼠体内外的主要代谢产物及代谢途径。方法 SD大鼠ig木兰花碱(50 mg/kg),收集0~24 h尿液和粪便,0~6 h胆汁以及1、2、4、6、8 h血浆;体外代谢采用肝微粒体温孵系统和肠菌培养液。利用LC-MS/MS对生物样品中的原型药及代谢产物进行鉴定。采用Agilent TC-C18色谱柱(150 mm×4.6 mm,5 μm),以乙腈-0.1%甲酸水溶液为流动相梯度洗脱,体积流量1.0 mL/min,柱温30℃。质谱采用电喷雾电离源(ESI),正离子采集模式;扫描范围m/z100~1 000。根据药物体内代谢规则,结合木兰花碱的色谱保留时间和多级质谱碎片离子特征,推测其代谢产物的结构。结果 给药后生物样品中共鉴定出12个代谢产物,其中Ⅰ相代谢产物8个,Ⅱ相代谢产物4个。主要的代谢途径为羟基化、去甲基化、脱氢作用、酮基化、葡萄糖化、葡萄糖醛酸化及硫酸酯化。结论 木兰花碱在体内可发生Ⅰ相和Ⅱ相代谢,肠道菌群和肝药酶可催化木兰花碱发生Ⅰ相代谢转化,Ⅱ相代谢存在于肠道以外部位,最有可能的部位是肝脏。  相似文献   

13.
袁芳  张志荣  杨云霞  黄园 《药学学报》2008,43(11):1152-1156
考察本实验室合成的N-(2-羟丙基)甲基丙烯酰胺[N-(2-hydroxypropyl) methacrylamide,HPMA]聚合物-5-氟尿嘧啶(5-flurouracil,5-FU)接合物(P-FU)的体外释药、体内分布及抗肿瘤活性。以小鼠血浆为介质,考察P-FU中5-FU的释放规律;以小鼠H22肝癌实体瘤模型(皮下型)为肿瘤模型,考察接合物在荷瘤小鼠体内的分布情况、药代动力学规律及抑瘤活性。结果表明,37 ℃时P-FU在小鼠血浆中具有一定的稳定性,半衰期(t1/2)为32.4 h。与5-FU相比,P-FU在荷瘤小鼠体内的循环时间明显延长(血浆中t1/2为原药的166倍),在肿瘤中的沉积量(AUC为5-FU的3.3倍)及滞留时间(t1/2为5-FU的2.3倍)均有明显增加。体内药效学研究表明,P-FU组对荷瘤小鼠的肿瘤生长抑制率(69.09%)显著高于5-FU组(56.49%,P<0.05),瘤块组织病理学观察结果也显示P-FU组小鼠肿瘤组织中细胞凋亡程度大于5-FU组。HPMA聚合物可被用于为5-FU构建一种新型实体瘤高分子给药系统。  相似文献   

14.
5-Fluorouracil (5-FU) is an antimetabolite with a broad-spectrum activity against solid tumors. However, its very short half-life in plasma circulation greatly limited the in vivo antitumor efficacy and clinical application. The current work aimed to solve this problem as well as to increase 5-FU biodistribution to tumor by covalently conjugating 5-FU to a biocompatible, non-toxic and non-immunogenic drug carrier – N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer. The in vitro cytotoxicity, in vivo biodistribution and therapeutic efficacy of HPMA copolymer–5-FU conjugates (P-FU) were reported. Cytotoxicity was evaluated by using a serial of tumor cells (A549, CT-26, Hela, HepG2 cells and 5-FU resistant HepG2 cells). In vivo biodistribution and therapeutic efficacy were investigated in Kunming mice-bearing hepatoma 22 (H22). Results indicated that P-FU could increase the cytotoxicity of 5-FU in Hela, HepG2 and 5-FU resistant HepG2 cells, while it decreases the cytotoxicity of 5-FU in A549 and CT-26. Both in vitro release profile in plasma and biodistribution study showed that P-FU significantly prolonged the drug plasma circulation time. P-FU also showed an over 3-fold larger area under the concentration–time curve (AUC) in tumor when compared with free drug. Therapeutic evaluation also demonstrated that the treatment with P-FU displayed stronger inhibition of the tumor growth when compared with that of control group (physiologic saline) or 5-FU group at the same dose. All the results suggested that P-FU could increase cytotoxicity of 5-FU in certain cancer cell lines, prolong 5-FU circulation time in vivo, enhance 5-FU distribution to tumor and improve therapeutic efficacy. Therefore, HPMA copolymer is a potential carrier for 5-FU for the effective treatment of cancer.  相似文献   

15.
目的 建立泻白散和方中3味主药甘草、地骨皮、桑白皮的体外抗氧化活性测定方法,并对31批药材和10批泻白散煎液的抗氧化活性进行测定。方法 采用紫外可见分光光度法检测一定浓度的药材提取液引起DPPH溶液吸光度(A)值降低,考察波长为517 nm,分别探索3味药材抗氧化活性成分的提取条件;并进行不同溶剂的吸收考察、专属性考察、DPPH线性考察、药材提取液线性考察、精密度试验、重复性试验、耐用性考察等方法学验证;以清除DPPH自由基的半抑制浓度(IC50)作为评价指标,对泻白散和方中3味药材的体外抗氧化活性进行考察。结果 地骨皮、甘草、桑白皮和泻白散提取液的IC50均值为0.31、1.24、1.49和0.91 g/L,泻白散提取工艺对方中药物抗氧化活性的保留均值为56%。结论 建立的抗氧化活性测定方法可用于泻白散及方中主药的抗氧化活性测定,为多维度评价中药和中药材质量提供新思路。  相似文献   

16.
The aim of the present study was to develop and evaluate a novel drug-in-adhesive transdermal patch system for indapamide. Initial in vitro experiments were conducted to optimize formulation parameters prior to transdermal delivery in rats. The effects of the type of adhesive and the content of permeation enhancers on indapamide transport across excised rat skin were evaluated. The results indicated that DURO-TAK® adhesive 87-2852 is a suitable and compatible polymer for the development of transdermal drug delivery systems for indapamide. The final formulation contained 4% N-dodecylazepan-2-one, 6% l-menthol and 3% isopropyl myristate. For in vivo studies patch systems were administered transdermally to rats while orally administered indapamide in suspension was used as a control. The PK parameters, such as the maximum blood concentration (Cmax), time to reach the peak blood concentration (Tmax), mean residence time (MRT), area under the curve (AUC0–t) and terminal elimination half-life (T1/2) were significantly (p < 0.05) different following transdermal administration compared with oral administration. In contrast to oral delivery, a sustained activity was observed over a period of 48 h after transdermal administration. This sustained activity was due to the controlled release of drug into the systemic circulation following transdermal administration.  相似文献   

17.
目的通过体外抗氧化活性检测,比较密蒙花与其替代品结香总提物体外抗氧化能力的差异。方法采用福林酚法测定密蒙花、结香总提物中总酚,并采用DPPH自由基清除能力法、ABTS清除能力法、Fe~(3+)还原能力法和Fe~(2+)螯合能力法分别测定两者体外抗氧化能力,选取维生素C和EDTA-Na_2作为阳性对照。结果密蒙花中总酚为结香的3~5倍;除亚铁离子螯合试验外,密蒙花的抗氧化作用均明显优于结香,这与总酚的量呈正相关性。结论两者总提取物中总酚和抗氧化能力差异显著,密蒙花明显优于结香。  相似文献   

18.
目的 建立瑞巴派特片体外溶出度HPLC检测方法及方法学验证。方法 溶出度试验采用桨法,转速50 r/min;以水、pH 1.2盐酸(含氯化钠)、pH6.0枸橼酸-磷酸二氢钠缓冲液和pH6.8磷酸缓冲液为溶出介质,HPLC法测定溶出量。结果 瑞巴派特在5.533~221.334 μg/mL内线性关系良好(r=0.999 9),专属性、精密度、准确度、溶液稳定性及耐用性等均良好。结论 本方法简单方便,提高了瑞巴派特溶出度测定的专属性和准确性,可用于该制剂的质量控制。  相似文献   

19.
The present investigation aims to establish efficacious screening strategy to clarify the phototoxic potential of pharmaceutical substances and its possible pathways by characterizing both photobiochemical properties and pharmacokinetic profiles. Photochemical behavior of griseofulvin, as model compounds, was evaluated by reactive oxygen species (ROS) assay, and the photogenotoxic potential was also assessed by DNA binding assay, DNA photocleavage assay, and atomic force microscopy. Pharmacokinetic (PK) study was also carried out after dermal and oral administration of griseofulvin in rats. ROS assay suggested the phototoxic potential of griseofulvin via type II photochemical pathways, and the photogenotoxic risk of griseofulvin was also proposed as evidenced by high affinity toward DNA and potent DNA photocleaving activity. PK profiling and in vivo phototoxicity testing demonstrated that a highly concentrated griseofulvin in the skin might cause phototoxic skin reactions in rats, whereas oral administration of griseofulvin in single dosing regimen (20 mg/kg) resulted in 103-fold less skin deposition than phototoxic skin concentration of griseofulvin. Upon these findings, the phototoxic potential of griseofulvin might not be severe at least in a single oral dosing regimen, whereas it might be phototoxic in dermal administration. The combination use of photobiochemical and pharmacokinetic data would be valuable to provide reliable prediction on phototoxic risk and possible toxic pathways of new drug entities in the early stage of drug discovery.  相似文献   

20.
Centaurea species are used for the treatment of various ailments in the popular medicine in some countries. This study was designed to examine antioxidant potentials and fatty acid profiles of five Centaurea species from Turkey flora. Antioxidant properties of methanolic extracts from these species were evaluated by six different methods: phosphomolybdenum assay, free radical scavenging assay, β-carotene/linoleic acid test system, metal chelating activity, ferric and cupric reducing power. Total phenolic and flavonoid concentrations of each extract were also determined using the Folin–Ciocalteu reagent and aluminum chloride. The results of these assay showed a significant antioxidant capacity in all researched extracts. Centaurea cheirolopha extract, with the highest amount of total phenolic and flavonoids, showed the highest antioxidant activities in all assay, except for metal chelating. Fatty acid profiles of these species were examined by GC–FID and 30 fatty acids were identified. Palmitic, linoleic, oleic, and linolenic acid were detected as the main components. The results of the study indicated that the Centaurea species can be considered as a source of new natural antioxidants and unsaturated fatty acids for food, cosmetic and pharmaceutical industries.  相似文献   

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