Albiflorin Granule significantly decreased the cholesterol gallstone formation by the regulation of insulin transduction signal

Objective:To study the mechanism of insulin resistance in the cholesterol gallstone formation from insulin signal transduction pathway so as to reveal the possible mechanism and the effective role of Albiflorin Granule on preventing the cholesterol gallstones.Methods:Serum triglycerides(TG),free fatty acid(FFA),and total cholesterol(TC) from different groups were measured and liver cells Ins R,PKB,IKK-β protein expression levels were detected by western blotting.Results:Albiflorin significantly decreased the cholesterol gallstone formation rate,increased glucose infusion rate in gallstone guinea pigs and improved insulin resistance.Compared with the normal group,insulin receptor and PKB protein expression in GS group were significantly reduced.IKK-β protein in the GS group increased significantly and Albiflorin could reduce IKK-β protein expression in guinea pig liver cells.Conclusions:The model of insulin resistance in cholesterol gallstone guinea pig was successfully established,which plays an important role in the cholesterol gallstone formation.All aspects of insulin signaling pathway are involved in gallstone formation.Albiflorin can regulate various aspects of insulin signal transduction pathway to prevent the formation of gallbladder.

Enhancement of exposure and reduction of elimination for paeoniflorin or albiflorin via co-administration with total peony glucosides and hypoxic pharmacokinetics comparison

OBJECTIVE Paeoniflorin(PF) and albiflorin(AF) are the major active components of total peony glucosides(TPG) from Paeonia lactiflora Pal,which have many biological activities such as anti-inflammatory,antioxidation and anti-hypertension effects.The drug-drug pharmacokinetic interaction among PF,AF and TPG,the pharmacokinetic comparisons of AF between hypoxia and normoxia,the transport of AF cross the blood-brain barrier cell model and the transport of AF/PF/TPG cross Caco-2 cell model were investigated.METHODS A highly sensitive and rapid UPLC-MS method with multiplereaction monitoring(MRM) scanning via electrospray ionization(ESI) source operating both in the positive and negative ionization mode was successfully developed and validated for simultaneous quantitation of PF and AF in rat plasma after an oral administration of PF,AF and TPG.RESULTS The validated and developed UPLC-MS/MS method was successfully applied to simultaneously determine the AF and PF concentration in rat plasma and investigate pharmacokinetic interactions after a single intragastrical ad.ministration of PF,AF,co-administration of PF with AF and TPG,respectively.The elimination of both PF co-administered with AF and PF in TPG were slower than those for PF alone and the distribution in the tissues was wider.The combination of PF with AF or TPG could significantly increase the values of the AUC,MRT and t1/2 of the drug PF,and reduce the values of CL of PF.From a comparison of the main pharmacokinetic parameters among AF alone,AF combined with PF and AF in TPG,the values of the MRT and t1/2 of AF in TPG were greater than that of AF alone,and there were statistically signifi.cant differences in these parameters(P<0.05,P<0.01).It was also noticed that AUC and Cmax of PF in hypoxia rats were significantly decreased compared with that of normaxia rats,suggesting that there was a decreased exposure of PF in rats under hypoxia.The multiple active components in TPG may lead to DDIs between some P-gp substrates.CONCLUSION The clinical performance of total peony glucosides would be better than that of single constitute.The outcomes of the study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.

Adsorption equilibria of paeoniflorin and albiflorin on cyano-silica column from supercritical carbon dioxide/ethanol

Adsorption equilibria of paeoniflorin and albiflorin on a cyano-silica column(CN column) from the solution of supercritical carbon dioxide(scCO2) modified with ethanol were studied. The adsorption capacity at 308.15 K,313.15 K, 318.15 K and 323.15 K under pressures corresponding to carbon dioxide/ethanol densities from0.347 g·cm^-3 to 0.662 g·cm^-3 were determined using the elution by characteristic point method(ECP). The effects of temperature and pressure on the solute loading were investigated. The results showed that the lower the temperature, the higher the adsorption capacity. With the decrease of density of scCO2, the adsorption capacity strengthens. The maximum adsorption capacity of paeoniflorin(albiflorin) on the CN column was15.24 mg·ml^-1(31.14 mg·ml^-1) in the range of 0–1.84 mg·ml^-1(0–1.67 mg·ml^-1) of paeoniflorin(albiflorin)standard solution. The adsorption capacity of albiflorin was twice as much as that of paeoniflorin under the same conditions. Adsorption data of paeoniflorin and albiflorin could be well described by the Langmuir model and Freundlich model. Compared with the two model fitting results, the adsorption of paeoniflorin and albiflorin belonged to the monolayer adsorption under conditions of 308.15–323.15 K and 10–17 MPa.

A comparison of pharmacokinetic interaction of paeoniflorin, albiflorin and total peony glucosides

Aim Paeoniflorin （PF） and albiflorin （AF） are the main components of total peony glucosides （TPG）, which has been widely used as the valuable monoterpene glycosides in Paeouia lactiflora Pall and have many biological activities such as anti-inflammatory, anti-hypertension and antioxidation effects. In this study, the pharmacokinetic interaction and possible interaction mechanism among Pie and A1e and TGP were conducted and in- vestigated. A sensitive and specific ultra high-performance liquid chromatography - tandem mass spectrometry method （UPLC-MS） was successfully developed and validated for simultaneous quantification of Pie and AF in rat plasma after intragastric administration and the comparative study of pharmacokinetics for PF and A1e in different combinations. The combinations of Pie （ 80 mg· kg^- 1 ）, Ale （ 14 mg ·kg^- 1 ）, co-administration of Pie （ 80 mg · kg^-1） and Ale （14 mg· kg^-1）, TPG （Pie 80 rag. kg^-1） and TPG （Alel4 mg.·1kg^-1） were orally administrated to rats respectively. Chromatographic separation was performed on a ZORBAX Eclipse plus Cls column using 0.2% formic acid-methanol （79：21, V/V） as mobile phase. The calibration curves were linear in ranges of 0.5 - 1000 μg · L^-1. The results indicated that the main pharmacokinetic parameters including AUC, MRT and tl/2 between the single ingredient （ Pie and Ale） and TPG had significant difference （ P 〈 0.05 or P 〈 0.01 ）. The different phar- macokinetics data implied that the multiple active components of TPG resulting some potential drug-drug interac- tions, which may promote the absorption and decease the elimination of Pie and Ale. Our results could be helpful for further investigation of the interaction mechanism of Pie and Ale.

Production of paeoniflorin and albiflorin by callus tissue culture of Paeonia lactiflora Pall

In order to facilitate the preparation of paeoniflorin(PF)and albiflorin(AF),two chief bioactive constituents in Paeonia lactiflora Pall(PL),induction and culture of callus from PL were studied.With a modified woody plant medium supplemented with 0.5 mg·L-16-benzylaminopurine,1.0 mg·L-1naphthylacetic acid,0.1 mg·L-1thidiazuron and 30 g·L-1sucrose,callus was induced from four kinds of explants:leaf,stems,petiole,and root.The potency to form callus varies between different explants and leaf explants exhibits the highest capacity(100%).On the other hand,root-derived callus(R-callus)produces the highest level of total amount of PF and AF,31.8 mg·g-1dry mass,which is higher than the corresponding level in the root of field cultivated PL.Furthermore,the time needed is only 40 days,remarkably shorter than the cultivation time of PL,about 4–5 years.Higher accumulation levels of PF and AF with shorter production time indicate that callus culture of PL is a promising powerful tool for production of PF and AF in the future.

Pharmacological effects of Paeoniflorin and Albiflorin on IL-3, GM-CSF, IL-6 and TNF-α in the rats of syndrome of stagnation of liver qi and blood deficiency

Objective： To observe the effect of paeoniflorin （PF）, albiflorin （AF） on the hemogram, visceral index and hematopoiesis cytokine in the rats of syndrome of stagnation of liver qi and blood deficiency, and to discuss the material base and mechanism of effect of nourishing blood and smoothing the liver of Baishao （Radix Paeoniae Alba）. Methods： Male SD rats were randomly divided into groups according to the sucrose preference test and body weight （n = 12）. Except the normal control, the other groups were treated with the chronic stress stimulation combined with radiation respectively to establish the model of syndrome of stagnation of liver qi and blood deficiency. The body weight, visceral index and the quantity of Leucocyte, Red Blood Cells, Hemoglobin in peripheral hemogram were monitored, then plasma and serum were separated. Radioimmunoassay was used to analyze the levels of Lnterleukin-3, Granulocyte-macrophage Colony-stimulating Factor, Lnterleukin-6 and Tumor Necrosis Factor-α in plasma. Results： Compared with that of model group, 30 mg·kg^-1 PF and 30 mg·kg^-1 AF of the weight, spleen index, quantity of Leucocyte were increased significantly （P 〈 0.05, P 〈 0.01）. The results of Radioimmunoassay showed that the levels of Interleukin-3 increased （P 〈 0.05, P 〈 0.05） and the levels of Tumor Necrosis Factor-α decreased in both 30 mg·kg^-1 PF and 30 mg·kg^-1 AF groups （P 〈 0.05, P 〈 0.05）. Conclusion： The effect of PF and AF on the regulation of bone marrow hematopoietic system and immune system play a role in the blood of rats with syndrome of stagnation of liver qi and blood deficiency, which suggests that both of them are the main active ingredients of nourishing blood and smoothing the liver of Baishao.

高效液相色谱法同时测定炒白芍中3种苷类成分

建立HPLC对炒白芍中3中苷类成分同时测定的分析方法。采用HPLC法;C18色谱柱;流动相:A为乙腈,B为0.1%磷酸溶液,梯度洗脱程序为:0 min(8%A),5 min(12%A),20 min(20%A),30 min(20%A),35 min(35%A),50 min(35%A);检测波长:230 nm;柱温:25℃。3种苷类成分的质量浓度与峰面积均呈良好的线性关系。平均回收率芍药苷为98.7%,RSD为2.1%;芍药内酯苷为98.7%,RSD为2.7%;苯甲酰芍药苷为99.1%,RSD为2.4%(n=6)。该方法分离度好,简便易行,具有良好的重现性,可用于白芍药材中3种苷类成分的同时测定。

UFLC法测定黄芪桂枝五物汤与芍药水提物中芍药苷和芍药内酯苷的含量

目的建立一种测定黄芪桂枝五物汤和芍药水提物中芍药苷和芍药内酯苷含量的超快速液相色谱法。方法采用ShimPack XR-ODS色谱柱,以0.1%磷酸水(A)和乙腈(B)作为流动相,梯度洗脱(0~5 min,10%-20%B;5~10 min,20%-25%B),平衡时间为5 min,流动相的流速为0.4 mL/min,色谱柱的温度设定为35℃,紫外检测器的波长设定为230 nm,进样量设定为5μL。结果芍药苷和芍药内酯苷的线性范围均为0.5~20 mg/L,所建立的分析方法具有较好的线性关系、精密度、稳定性和回收率。黄芪桂枝五物汤和芍药水提物中芍药苷的含量分别为2.75~3.84 g/L和4.70~4.99 g/L,芍药内酯苷的含量分别为0.632~0.928g/L和0.729~0.870 g/L。结论芍药苷在黄芪桂枝五物汤中比在芍药水提物中的含量少,表明其它药材成分对芍药苷的提取具有抑制作用。芍药内酯苷在黄芪桂枝五物汤中和在芍药水提物中含量无明显差异。本方法分析时间短、稳定性好,可用于黄芪桂枝五物汤的质量控制和配伍规律研究。

白芍苷R1体外抗细胞增殖活性初步研究

[目的]观察白芍苷R1的体外抗细胞增殖药理活性。[方法]采用HeLa、K562两种癌细胞株以及小鼠巨噬细胞株J774体外培养进行细胞增殖实验,对白芍苷R1的体外药理活性进行观察。[结果]白芍苷R1对两种癌细胞株的增殖均有一定的抑制作用,对J774巨噬细胞增殖有较强的抑制作用。[结论]白芍苷R1可能具有一定的抗肿瘤和抗炎免疫抑制活性。

白芍中的一种新的单萜苷

目的 研究中药白芍的化学成分。方法 用现代色谱分离方法进行化学成分分离 ,并通过理化性质和各种色谱学分析鉴定化合物的结构。结果 从中药白芍中分离得到一种苷元与葡萄糖 2位相连成苷的单萜苷类化合物白芍苷R1 。结论 白芍苷R1

不同种质和不同部位白芍原植物中芍药苷和芍药内酯苷的含量测定

目的比较不同种质、不同部位白芍原植物在同一分析方法下芍药苷、芍药内酯苷的含量差异及分布情况。方法采用高效液相色谱法,色谱条件:Lichro CART RP-C18(4 mm×250 mm,5μm);流动相:乙腈-0.1%磷酸溶液(14∶86);流速:1.0 mL.min-1;检测波长:230 nm;柱温:30℃;进样量:10μL。结果不同种质白芍原植物中芍药苷、芍药内酯苷含量存在较大差异,白芍原植物地下各部分芍药苷的含量呈现根茎(芍头)>须根>主根,芍药内酯苷的含量呈现须根>根茎(芍头)>主根。结论芍药苷、芍药内酯苷含量差异主要影响因素为种质,道地产区的种质芍药苷、芍药内酯苷含量变异幅度小。

HPLC法测定白芍总苷胶囊中芍药内酯苷、芍药苷和苯甲酰芍药苷

目的建立HPLC对白芍总苷胶囊中芍药内酯苷、芍药苷和苯甲酰芍药苷同时定量的分析方法。方法采用HPLC法。色谱柱Zorbax SB-C18色谱柱(250mm×4.6mm,5μm);流动相A为乙腈,B为0.015%磷酸溶液,梯度洗脱程序为0min(8%A),5min(12%A),20min(20%A),25min(20%A);35min(45%A),40min(45%A);检测波长230nm;柱温30℃。结果芍药内酯苷、芍药苷和苯甲酰芍药苷质量浓度与峰面积均呈良好的线性关系。平均回收率芍药内酯苷为96.99%,RSD为0.56%;芍药苷为103.6%,RSD为0.77%;苯甲酰芍药苷为104.2%,RSD为1.35%(n=5)。结论该方法分离度好,简便易行,具有良好的重现性,可用于白芍总苷胶囊中芍药内酯苷、芍药苷和苯甲酰芍药苷的同时测定。

液相色谱-质谱联用测定大鼠血浆中芍药内酯苷及其药动学研究

目的建立大鼠血浆中芍药内酯苷的HPLC-MS/MS定量分析方法,并用于大鼠体内芍药内酯苷药动学研究。方法血浆样品采用固相萃取预处理。色谱柱为Symmetry C18(4.6mm×50mm,3.5μm),流动相为乙腈-0.05%甲酸溶液(25∶75)。采用三重四极杆质谱仪进行多反应监测方式(MRM),电喷雾离子源。对所建方法进行了较全面的验证。考察了3种剂量芍药内酯苷给与大鼠后的药动学特征。结果所建方法灵敏、重现性良好。芍药内酯苷在体内吸收迅速,消除也较快。经统计学检验表明,在给定的3个剂量范围内,芍药内酯苷具有线性动力学特征。结论建立的方法可用于芍药内酯苷的药动学研究。

不同等级杭白芍中3个有效成分的考察

目的比较不同等级杭白芍药材中儿茶素、芍药内酯苷、芍药苷3个有效成分的量。方法参照《七十六种药材商品规格标准》将所收集的杭白芍分为六个等级,采用高效液相色谱法测定杭白芍中3个有效成分的量。结果不同等级的杭白芍药材中3个成分的量没有规律性,以芍药苷为例,六等品样品(2-6)中芍药苷的量最高,远高于一等品(2-1)样品中的芍药苷的量。结论目前,杭白芍的等级划分标准不能全面的反映杭白芍的自身品质,也不符合按质论价的商业需求,应该结合药材中成分含有量来制定药材规格等级标准。

白芍总苷在免疫性肝损伤大鼠体内的药代动力学研究

目的比较白芍总苷(TGP)在免疫性肝损伤大鼠和正常大鼠体内药动学参数的异同,为临床制定给药方案提供参考。方法采用猪血清腹腔注射法建立大鼠免疫性肝损伤模型,以HPLC法测定模型大鼠和正常大鼠灌胃给予3个剂量白芍总苷后15、30、60、90、120、150、180、240、360、480、720min血浆中芍药苷和芍药内酯苷浓度,根据药时曲线计算药动学参数,采用SPSS 11.5软件分析各组各剂量间药动学参数异同。结果与正常组相比,模型组大鼠体内白芍总苷的Cmax、AUC0-t和AUC0-∞明显增大,Tmax明显提前,T12明显延长;各剂量间白芍总苷Tmax和T21没有差异,剂量与Cmax、AUC0-t和AUC0-∞有一定的相关性。结论肝损伤大鼠对TGP的吸收速度较正常大鼠快,吸收量较大,消除较慢,提示临床要针对不同的机体状态,设计合理安全的剂量,以免给药量过大引起蓄积和毒性反应。

党参、黄芪、白术提取物配伍应用对小肠上皮细胞增殖的影响

[目的]观察党参、黄芪、白术有效组分配伍对小肠隐窝细胞株(IEC-6)细胞增殖的影响。[方法]IEC-6以每孔50μL-1的密度接种200μL于96孔培养板,每组3孔。24h后加入不同剂量的各种有效组分及其配伍溶液10μL,空白组加等量Dulbecco’s磷酸缓冲液。加药后24 h用噻唑蓝(MTT)比色法观察细胞增殖情况。[结果]来源于不同药物或同一药物的两个有效组分配伍应用,对IEC-6细胞的增殖作用表现各异,有的协同促进,有的协同抑制,有的作用相互抵消,有的作用方向改变,有的作用无明显改变。[结论]党参、黄芪、白术不同提取部位配伍应用对IEC-6细胞增殖具有调控作用。

不同产地白芍HPLC指纹图谱及芍药苷和芍药内酯苷含量的比较研究

目的建立湘白芍、亳白芍与杭白芍HPLC指纹图谱分析方法,并对3种不同产地药材进行主要化学成分的比较。方法采用HPLC对11批白芍样品进行指纹图谱分析,并测定了主要化学成分芍药苷和芍药内酯苷的含量。结果所建立的方法精密度、稳定性和重现性良好;11批白芍样品的指纹图谱有8个共有峰。结论通过建立白芍指纹图谱的定性、芍药苷及芍药内酯苷的定量,为白芍的质量控制提供了更为全面的方法。

石菖蒲冰片对神经细胞缺氧性损伤的保护作用

[目的]探讨石菖蒲、冰片对缺氧损伤神经细胞的保护作用。[方法]在缺氧培养条件下造成大鼠神经细胞损伤,测定空白对照组、模型对照组、石菖蒲挥发油组、冰片组、冰片+石菖蒲挥发油(低、中、高配比)组神经元细胞数、神经细胞支配面积。[结果]石菖蒲挥发油、冰片、冰片+挥发油(低、中、高配比)给药组神经细胞支配面积和神经元细胞数高于空白对照组和模型对照组。[结论]石菖蒲、冰片对缺氧诱导的大鼠神经细胞损伤具有保护作用。

基于分子对接技术探讨赤芍治疗胆汁淤积型肝炎作用机制的研究

目的:利用分子对接技术,探讨赤芍中的芍药苷、芍药内酯苷、丹皮酚等4种有效成分分别与法尼酯衍生物X受体(farnesoid X receptor,FXR)的相互作用。方法:采用Autodock 4.2软件进行分子对接。结果:得出芍药苷、芍药内酯苷、丹皮酚等与FXR蛋白1号位点和2号位点以及FXRα蛋白的结合结果。芍药苷、芍药内酯苷、丹皮酚与FXRα蛋白结合的自由能分别为-13.44、-21.77、-16.45 k J/mol,与FXR蛋白1号位点的自由能分别为-18.21、-48.60、-49.52 k J/mol,与FXR蛋白2号位点的自由能分别为-15.32、-24.70、-18.59 k J/mol。结论:芍药苷、芍药内酯苷、丹皮酚与FXR蛋白具有较小的自由能,即结合作用较强。提示赤芍治疗胆汁淤积型肝炎的作用机制可能为其主要成分与FXR受体蛋白具有较强结合作用,引起FXR调节其相应靶基因的表达,从而调控胆汁酸的合成和代谢以达到保肝利胆的作用,为进一步研究赤芍治疗胆汁淤积型肝炎的分子机制提供了理论参考。

赤芍中芍药苷和芍药内酯苷的代谢及药动学研究进展

药物代谢是药物研发过程的重要环节,对于深入探讨药物的药效基础及在体内的代谢规律至关重要.芍药苷和芍药内酯苷是赤芍的主要活性成分,具有广泛的药理作用.文章通过查阅国内外文献,就其体内、体外代谢及药代动力学方面进行综述,介绍了芍药苷和芍药内酯苷体内、体外代谢机制,旨在为赤芍的研发和临床给药提供科学依据,同时也为其他药物的代谢研究提供参考.