赤芍总苷对大鼠缺血损伤心肌细胞凋亡的保护作用

目的研究赤芍总苷(TPG)对异丙基肾上腺素(ISO)诱导的心肌缺血损伤大鼠细胞凋亡的保护作用及其机制。方法Rona法复制大鼠心肌缺血损伤模型,检测和对比分析正常对照组、ISO损伤组、TPG防治组、TPG治疗组和心得安阳性对照组的心肌细胞早期凋亡率、心肌组织凋亡相关基因Bax、Bcl-2及其蛋白的相对表达量。结果与ISO损伤组比较,TPG防治组和治疗组各项指标均有不同程度的改善,表现为大鼠早期心肌细胞凋亡率和促凋亡基因Bax及其蛋白的表达量明显降低,而抑凋亡基因Bcl-2及其蛋白的表达量有所增高,Bcl-2/Bax蛋白比值明显高于ISO损伤组。结论TPG对ISO诱导的大鼠心肌缺血损伤时的细胞凋亡具有保护作用,药用机制可能与激活Bcl-2基因及其蛋白表达,抑制Bax基因及其蛋白表达,提高Bcl-2/Bax蛋白比值,从而有效抑制心肌细胞凋亡有关。     

赤芍总苷对培养乳鼠心肌细胞损伤的抗氧化作用

目的　探讨赤芍总苷对心肌细胞损伤的抗氧化保护作用。方法　以培养的乳鼠心肌细胞加入异丙基肾上腺素造成缺血缺氧损伤模型 ,对比分析正常对照组、药物损伤组、辅酶Q10 阳性对照组、以及不同剂量赤芍总苷保护组培养液中超氧化物歧化酶、丙二醛和一氧化氮含量。结果　损伤组总SOD、CuZn SOD和Mn SOD水平均明显下降 ,MDA和NO含量显著升高 ;而辅酶Q10 组和赤芍总苷组上述指标都有不同程度的改善 ,其中大剂量赤芍总苷组的保护作用接近或优于阳性对照组。结论　赤芍总苷对异丙基肾上腺素造成的心肌损伤具有保护作用 ,且呈现剂量依赖关系 ,作用机制与增强细胞抗氧化作用 ,减少自由基和脂质过氧化物导致的细胞膜损伤有关。     

赤芍总苷对小鼠学习记忆能力的改善作用

目的　观察赤芍总苷对小鼠学习记忆能力的影响。方法　选用东莨菪碱所致小鼠记忆获得 ,环己酰亚胺所致记忆巩固 ,乙醇所致记忆再现障碍模型及戊巴比妥钠所致空间分辨障碍模型。结果　赤芍总苷显著减少上述记忆障碍小鼠受刺激时间 ,延长平台停留期 ,减少错误次数 ,并调节反应潜伏期 ;对空间分辨障碍小鼠 ,赤芍总苷具有一定增加达岸成功率 ,减少错误次数及缩短达岸时间的作用。结论　赤芍总苷对药物所致小鼠学习记忆障碍有明显的改善作用     

赤芍总苷与黄芪多糖配伍抑制血小板聚集的药效优化

目的:研究赤芍总苷与黄芪多糖抑制血小板聚集的机制及其最佳配伍水平.方法:在对赤芍总苷与黄芪多糖分别采用不同剂量单味药实验的基础上,通过二次回归正交组合设计对赤芍总苷与黄芪多糖不同剂量配伍进行实验和分析.结果:赤芍总苷与黄芪多糖分别随着剂量的增加都能显著降低血小板的聚集率,赤芍总苷最佳剂量为125mg·kg-1,黄芪多糖...     

Preparation,characterization and pharmacokinetics of 10-hydroxy-camptothecin nanosuspension

10-Hydroxycamptothecin (HCPT) is a broad-spectrum anticancer drug, while its low solubility and instability severely limit its application. In this study, HCPT nanosuspension (HCPT-NSP), also known as nanocrystal, was prepared by micro-precipitationcombined with high-pressure homogenization method. This nanosuspension was characterized by size, shape, zeta potential, drug loading efficiency and in vitro drug release behavior. Preferred formulation and process showed that particle size was (129.8±13.9) nm, PDI was 0.20±0.07, and drug loading efficiency was 36.5%±9.5%. Moreover, HCPT nanocrystal concentration reached(1.35±0.2) mg/mL in HCPT-NSP, which was more than 1000-fold higher than that of HCPT. Transmission electron microscopy (TEM) results showed that the nanosuspension was short rod in shape. X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), derivative thermogravimetric analysis (DTA) and differential scanning calorimetry (DSC) further elaborated the crystal state of the HCPT. The drug concentration-time curve of HCPT-NSP in rats was in accordance with the three-compartment model, showing prolonged half-life. Taken together, our data suggested that HCPT-NSP was a promising drug delivery system.     

高效液相色谱法测定赤芍中赤芍总苷的含量

目的研究用高效液相色谱法测定赤芍总苷(TPG)含量的可行性.方法赤芍经70%乙醇提取后大孔吸附树脂分离以制备TPG;采用高效液相色谱法(HPLC)测定赤芍总苷中芍药苷含量,色谱条件:S-Gel C18,5 μm色谱柱,流动相:甲醇-水(50∶ 50),柱温40℃,流速0.8 ml·min-1,检测波长230 nm.结果大孔吸附树脂分离赤芍总苷(TPG)的制备工艺质量稳定;HPLC法准确、可靠、重现性好,平均回收率为100.1%,RSD为1.96%.结论建立的方法可用以控制赤芍总苷质量.     

赤芍总甙对原代培养大鼠神经细胞损伤模型的保护作用

目的 探讨赤芍总甙对大鼠神经细胞脑缺血样损伤模型的保护作用及其机制。方法 采用组织培养法,以原代大鼠大脑皮层神经细胞为材料,制备缺糖损伤、缺氧损伤、自由基损伤、咖啡因损伤、一氧化氮损伤及NMDA毒性损伤模型。结果 形态学检查发现赤芍总甙（total paeony glycoside,TPG)对6种脑缺血样损伤模型中的大鼠神经细胞具有明显保护作用,结晶紫染色也提示TPG可显提高损伤模型中神经细胞的存活数。结论 TPG对上述6种大鼠神经细胞缺血损伤均有显的保护作用。     

赤芍总苷对D-半乳糖衰老小鼠学习记忆及代谢产物的影响

目的　观察赤芍总苷对D 半乳糖所致衰老小鼠学习记忆及与神经介质调节相关酶及代谢产物的影响。方法　选用长期皮下注射D 半乳糖形成的衰老小鼠模型。结果　赤芍总苷对衰老小鼠的学习记忆障碍有显著的改善作用 ,穿梭试验中小鼠主动回避潜伏期和主动回避次数明显增加 ;水迷宫试验发现 ,赤芍总苷可有效提高小鼠的达岸正确率 ,减少小鼠的错误次数。赤芍总苷可显著降低衰老小鼠脑组织中单胺氧化酶 (MAO)水平 ,提高胆碱酯酶 (CHE)活性 ;并抑制脂质过氧化产物丙二醛 (MDA)含量的增加 ,提高脑组织超氧化物岐化酶 (SOD)水平。此外 ,赤芍总苷对衰老小鼠免疫功能低下及脑萎缩状态有显著的改善。结论　赤芍总苷具有抗衰老及促进学习记忆能力的作用     

大孔树脂纯化白芍总苷的研究

目的筛选影响白芍总苷分离的主要因素。方法用大孔树脂吸附分离纯化白芍总苷,选用了均匀设计法,对洗脱工艺参数进行优选。结果最佳上柱工艺为药液浓度1g生药材／ml,2倍树脂量吸附,柱径高比为1：12,吸附时间30min。结论大孔树脂可较好地富集白芍中的总苷,其膏中总苷含量达60％以上。     

Preparation,characterization and pharmacokinetic studies of linalool-loaded nanostructured lipid carriers

Context Linalool (LL) is associated with numerous pharmacological activities. However, its poor solubility usually results in poor bioavailability, and further limited its applications.

Objective To reduce volatilization and improve bioavailability of LL, linalool-loaded nanostructured lipid carriers (LL-NLCs) were prepared.

Materials and methods LL-NLCs were prepared using high-pressure homogenization method and optimized via response surface methodology-central composite design, followed by characterization, including particle size (PS), zeta potential (ZP), transmission electron microscope (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and in vitro release study. Rats were administered 300?mg?×?kg?^??¹ LL with each preparation (LL-NLCs or LL) via oral gavage.

Results LL-NLCs had a PS of 52.72?nm with polydispersity index of 0.172, and ZP of –16.0?mV. The encapsulation efficiency and drug loading gave 79.563 and 7.555%, respectively. The cumulative release of LL from free LL reached 51.414% at 180?min, while LL from LL-NLCs was 15.564%. All the pharmacokinetics parameters of LL-NLCs were better than those of LL, including C_max (from 1915.45 to 2182.45?ng?×?mL?^??¹), AUC_0–t (from 76003.40 to 298948.46?ng?×?min?×?mL?^??¹) and relative bioavailability (393.34%). The t_1/2, MRT and t_max of LL-NLCs (110.50, 146.66 and 60?min) were also longer than that of LL (44.72, 45.66 and 40?min).

Discussion and conclusion LL-NLCs were for the first time prepared and its oral administration in rats thoroughly investigated. LL-NLCs exhibited sustained release effect and increased absorption of LL. Therefore, these findings might provide a potential possibility for clinical application of LL.     

白芍总甙对T细胞调节功能的影响

本文用超适量免疫及~(60)Co照射加输注受训胸腺细胞等方法,诱导抗原特异性T_s和T_h细胞,并经过继性转移系统测定其功能及自芍总甙的作用,结果表明,白芍总甙(5 mg·kg~(-1)·d~(-1)×8 d,ip)对超适量2,4-二硝基氯苯(3 mg)或羊红细胞(SRBC,4×10~9)诱导的环磷酰胺敏感的T_s细胞均有促进作用,前者表现为受体鼠的耳肿度(Δwt7.4±s2.8mg)与ConA诱导的脾淋巴细胞增殖反应(3.4±s0.9)×10~(-3)cpm明显分别低于溶媒对照组的耳肿度(Δwt13.6±s3.2mg)和淋巴细胞转化(10.9±s2.8)×10~(-3)cpm,后者表现为溶血素抗体生成(A 0.26±s0.05)明显低于溶媒对照组,白芍总甙(5mg·kg~(-1)·d~(-)×10 d,ip)对小鼠辐照后低剂量SRBC(2×10~8)诱导的T_h细胞亦有增强作用,使受体鼠的溶血素抗体生成(A 0.74±s 0.10)明显高于溶媒对照组(A 0.57±s 0.06),提示白芍总甙对不同条件下分别诱导的T_s和T_h细胞均有促进作用,这可能是其发挥免疫调节作用的机理之一。     

白芍总苷对动脉粥样硬化大鼠氧化应激和炎症反应的抑制作用

目的研究白芍总苷(Total glucosides of paeony,TGP)对动脉粥样硬化大鼠氧化应激和炎症反应的抑制作用及其机制。方法应用高脂饲料喂养结合腹腔注射维生素D3建立大鼠动脉粥样硬化(AS)模型,造模过程分别同步灌胃给予TGP 50、100、200 mg/(kg·d)和辛伐他汀(SV)1.8 mg/(kg·d),共12周,并设模型组和正常对照组。采用HE染色法观察主动脉形态结构改变并进行病变分级;比色法测定血清中抗氧化酶活性和丙二醛(MDA)、活性氧簇(ROS)含量;酶联免疫法测定血浆中炎症细胞因子含量。结果与模型组比较,TGP干预组大鼠主动脉病理性形态结构改变呈不同程度改善,其中以TGP 200 mg/(kg·d)组最为显著。TGP 100、200 mg/(kg·d)组病变分级显著降低,血清中抗氧化酶[超氧化物歧化酶(SOD)、过氧化氢酶(CAT)]活性显著升高,MDA、ROS含量均降低。其中,TGP 200 mg/(kg·d)组谷胱甘肽过氧化物酶(GSH-Px)活性升高,TGP 100、200 mg/(kg·d)组大鼠血浆中C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、IL-6含量降低,且TGP200 mg/(kg·d)组炎症细胞因子(IL-10)含量升高,差异均有统计学意义(P<0.05,P<0.01)。结论 TGP能够通过抑制氧化应激和炎症反应而对动脉粥样硬化表现出一定的保护作用。     

白芍总苷对NAFLD大鼠肝脏的保护作用及其机制研究

目的研究白芍总苷对NAFLD模型大鼠肝脏保护的机制。方法 SD大鼠50只,随机分为正常对照组10只,模型组40只。高脂饲料喂养建模后,模型组随机分为模型对照组、非诺贝特组、白芍总苷高剂量组、白芍总苷低剂量组各10只。连续灌胃给药4周后,测定大鼠血清中ALT、AST、GST、SOD和GSH-PX酶的活性及MDA含量;测定血清中IL-1、TNF-α和TGF-β的水平;各组取肝脏做HE染色,观察肝脏组织学病变。结果与正常对照组比较,NAFLD模型对照组大鼠ALT、AST、GST活性和IL-1、TNF-α、TGF-β含量显著升高,经非诺贝特和白芍总苷干预后,模型组大鼠的ALT、AST、GST活性和IL-1、TNF-α、TGF-β含量均降低回正常水平,差异有统计学意义(P<0.05);与正常对照组比较,NALFD模型大鼠SOD、GSH-PX活性显著降低,MDA含量明显升高,干预治疗后,模型组大鼠SOD、GSH-PX活性大大提高,MDA含量显著降低(P<0.05)。结论白芍总苷对高脂引起的NAFLD模型大鼠有肝脏保护作用,其作用机制可能与其提高抗氧化能力、降低异常细胞因子水平有关。     

咪唑斯汀联合白芍总苷胶囊治疗慢性特发性荨麻疹临床疗效观察

目的：观察咪唑斯汀联合口服白芍总苷胶囊治疗慢性特发性荨麻疹的疗效。方法：选择120例慢性特发性荨麻疹患者,按就诊顺序分为两组,治疗组给予咪唑斯汀联合口服白芍总苷胶囊,对照组单一给予咪唑斯汀。结果：治疗结束时治疗组有效率为88％,对照组有效率为87％,两者之间差异无统计学意义;治疗结束后3个月治疗组复发率为43．37％,对照组复发率为71．20％,两者之间差异有统计学意义（P〈0．01）。结论：咪唑斯汀联合口服白芍总苷胶囊可能对慢性特发性荨麻疹治疗、预防复发有一定的作用。     

Pharmacokinetic and tissue distribution studies of paeoniflorin and albiflorin in rats after oral administration of total glycosides of paeony by HPLC-MS/MS

A simple, sensitive and specific high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method combined with solid phase extraction has been developed and validated for the simultaneous quantification of paeoniflorin and albiflorin in rats plasma and tissue homogenate after administration of total glycosides of paeony (TGP). Chromatographic separation was achieved on a C₁₈column (150 mm×4.6 mm, 5 μm) with mobile phase consisted of acetonitrile–0.05% formic acid aqueous (20: 80, v/v) at a flow rate of 0.5 mL/min. The analytes were detected with triple-quadrupole mass spectrometer using turbo ion spray with negative ionization in the multiple reaction-monitoring (MRM) modes. The results of method validationconformed to the requirements for the determination of biological samples. This method was successfully applied to the pharmacokinetics and tissue distribution study of TGP in rats. The results showed that paeoniflorin and albiflorin were absorbed and reached peak value quickly, and had the similar pharmacokinetic characteristics. Both of them underwent a rapid and wide distribution in the tissues throughout the whole body, among which stomach was the main distribution tissue. Moreover, they had the ability to cross the blood-brain barrier.     

沙利度胺、白芍总苷、柳氮磺吡啶联合治疗对强直性脊柱炎患者病情活动度的影响

目的探讨沙利度胺、白芍总苷、柳氮磺吡啶联合治疗对强直性脊柱炎(AS)患者病情活动度的影响。方法78例首诊为AS患者,经随机数字表法分为A组与B组,各39例。A组患者接受沙利度胺、柳氮磺吡啶联合治疗,B组患者接受沙利度胺、白芍总苷、柳氮磺吡啶联合治疗。对比两组患者的基于C反应蛋白(CRP)计算的AS疾病活动度评分(ASDAS)(ASDAS-CRP)评分、疾病活动度、治疗前后实验室指标[CRP、肿瘤坏死因子-α(TNF-α)、血沉(ESR)、骨钙素(BGP)、Ⅰ型胶原C末端肽(CTX-Ⅰ)]水平。结果治疗12周后,B组患者的ASDAS-CRP评分(1.39±0.21)分低于A组的(1.63±0.27)分,差异有统计学意义(P<0.05)。B组患者的疾病活动度分级情况优于A组,差异有统计学意义(P<0.05)。治疗12周后,A组患者的CRP、TNF-α、ESR、BGP、CTX-Ⅰ水平分别为(10.88±1.76)mg/L、(7.11±1.67)pg/ml、(19.92±2.17)mm/h、(4.20±0.56)pg/ml、(8.25±0.92)pg/ml,B组患者分别为(8.36±0.94)mg/L、(5.36±0.72)pg/ml、(14.36±1.50)mm/h、(3.07±0.45)pg/ml、(5.88±0.71)pg/ml,治疗12周后,两组患者的CRP、TNF-α、ESR、BGP、CTX-Ⅰ水平均低于治疗前,且B组患者低于A组,差异均有统计学意义(P<0.05)。结论沙利度胺、白芍总苷、柳氮磺吡啶联合治疗可有效抑制AS患者的病情活动。     

奈韦拉平纳米混悬液的制备及大鼠体内药动学研究

目的：：制备奈韦拉平纳米混悬剂,考察其在大鼠口服给药后体内的药动学特征。方法：采用高压均质法制备奈韦拉平纳米混悬剂,以纳米混悬剂粒径分布、PdI和Zeta电位为指标,考察了奈韦拉平纳米混悬剂的影响因素,并对制得的纳米粒进行表征;采用高效液相色谱法测定大鼠血浆中的奈韦拉平浓度,使用3P97软件计算相应的药动学参数。结果：奈韦拉平纳米混悬液平均粒径为(456.1±72.1) nm,PdI为(0.441±0.072),Zeta电位为(-24.4±4.7) mV。奈韦拉平混悬液和奈韦拉平纳米混悬剂在大鼠体内的AUC0-12分别为(7.57±0.52)和(11.72±1.83) mg·h·L-1;t1/2分别为(2.45±0.31)和(3.16±0.39) h;Tmax分别为(1.43±0.38)和(1.61±0.32) h;Cmax分别为(1.62±0.42)和(3.15±0.52) mg·L-1。结论：奈韦拉平纳米混悬液能够明显改善大鼠体内奈韦拉平的药动学行为,与奈韦拉平混悬液相比显著提高了药物的生物利用度。     

白芍总苷联合甘草酸苷治疗亚急性湿疹的临床研究

目的探讨白芍总苷联合甘草酸苷治疗亚急性湿疹的临床疗效。方法选择本院2009年2月～2011年8月收治的亚急性湿疹患者210例,按照就诊顺序分为3组,每组70例。A组患者采取甘草酸苷注射液静脉点滴进行对症治疗,B组患者给予白芍总苷胶囊进行对症治疗,C组患者给予静脉点滴甘草酸苷注射液联合口服白芍总苷胶囊;均连续治疗1个月后,观察3组患者治疗前后的主要体征变化,检测3组患者治疗前后的血清IgE定量、嗜酸粒细胞计数等。结果治疗后,C组患者的临床症状积分、血清IgE以及嗜酸粒细胞计数均明显低于A组和B组（P〈0.05）。结论白芍总苷联合甘草酸苷治疗可有效缓解亚急性湿疹症状,临床疗效确切,不良反应小,值得推广应用。     

First total synthesis of a new phenylpropanoid glycoside: natural cytotoxic compound from Cirsium japonicum

Abstract

Phenylpropanoid glycoside compound 1, the natural anti-tumor compound isolated from the erial parts of Cirsium japonicum, was first totally synthesized using easily available materials in short, convenient route with overall yield of 13.9%.     

Preparation and characterization of intravenously injectable nimodipine nanosuspension

The purpose of this study was to develop an alternative, improved and better tolerated injectable nimodipine nanosuspension compared with commercially available ethanol solution. In this study, nimodipine nanosuspension was prepared by high-pressure homogenization (HPH). The effects of the production parameters such as pressure, cycle numbers and crushing principles on the mean particle size, 99% diameter and polydispersity of the nanosuspension were investigated. Characterization of the product was performed by scanning electron microscope (SEM) and differential scanning calorimeter (DSC). The safety of the nimodipine nanosuspension was discussed with special attention to contamination by microparticles and the increase in saturation solubility C_s. Irritability study in rabbits showed that this formulation provided less local irritation and phlebitis risks than the commercial ethanol product, which represented a promising new drug formulation for intravenous therapy of subarachnoid hemorrhage (SAH)-related vasospasm.