益气解毒化瘀小复方及其单味药对大鼠肾小球系膜细胞Smad3,Smad7mRNA的影响研究

目的:探讨益气解毒化瘀小复方及其单味药对血管紧张素Ⅱ诱导的大鼠肾小球系膜细胞信号通路Smad3,Smad7mRNA的基因表达影响,初步明确其抗肾小球硬化的作用机理。方法:常规培养大鼠肾小球系膜细胞(GMCs),RT-PCR法检测Smad3,Smad7mRNA表达。结果:小复方组抑制系膜细胞Smad3mRNA的表达最为明显,促进Smad7mRNA表达最为明显,与各单味药组、西药对照组比较,有显著性差异(P 0. 01或P 0. 05)。结论:益气解毒化瘀小复方可有效地抑制肾小球系膜细胞Smad3mRNA的表达,有效地促进系膜细胞Smad7mRNA表达,并优于单味药,从而达到抗肾小球硬化,保护肾脏的目的。     

益气化瘀清热方及其拆方对大鼠肾小球系膜细胞表达p38MAPKmRNA及其蛋白的影响

目的:对益气化瘀清热方进行拆方,通过观察各类含药血清对脂多糖(lipopolysaccharide,LPS)诱导下体外培养的大鼠肾小球系膜细胞(primary mesangial cells,Ms C)表达p38MAPKmRNA及其蛋白的影响,探讨不同中药的作用强度以及益气化瘀清热方治疗肾小球肾炎的作用机制。方法:RT-PCR法检测各组含药血清对Ms C表达的p38MAPK mRNA。Wersten Blot法检测各组含药血清对大鼠Ms C表达的p38MAPK蛋白。结果:1RT-PCR结果显示:各组含药血清均能抑制体外培养的Ms C表达p38MAPKmRNA,复方组作用最强(P0.01),清热组与化瘀组比较无明显差异(P0.05),但优于益气组,差异显著(P0.01);2 Wersten印迹结果显示:各组含药血清均能抑制体外培养的Ms C表达p38MAPK蛋白,复方组作用最强(P0.01),清热组与化瘀组比较无明显差异(P0.05),但优于益气组,差异有统计学意义(P0.01)。结论:各类含药血清对大鼠Ms C表达p38MAPK mRNA及其蛋白的影响在不同组中药的比较中,复方组作用最强,化瘀组和清热组的作用明显优于益气组。     

糖肾汤对糖基化蛋白诱导培养下系膜细胞表达金属蛋白酶组织抑制物1、2的影响

目的:研究糖基化蛋白诱导培养下,糖肾汤对大鼠肾小球系膜细胞表达基质金属蛋白酶组织抑制物1、2(TIMP1、TIMP2)mRNA的影响。方法:采用血清药理学及体外大鼠肾小球系膜细胞培养方法,用糖基化牛血清白蛋白(AGE-BSA)刺激肾小球系膜细胞,采用RT-PCR法检测系膜细胞TIMP1、TIMP2 mRNA表达。结果:糖基化蛋白可上调TIMP1、TIMP2 mRNA表达,糖肾汤能降低TIMP1、2mRNA表达。结论:糖肾汤对金属蛋白酶系统紊乱有一定的调节作用。     

益气化瘀清热方及其拆方对大鼠肾小球系膜细胞TGF-β1/Smad3信号通路的影响

目的:对益气化瘀清热方进行拆方,通过观察各类含药血清对脂多糖(lipopolysaccharide,LPS)诱导下体外培养的大鼠肾小球系膜细胞(primary mesangial cells,Ms C)表达TGF-β1及Smad3蛋白的影响,探讨不同类中药的作用强度以及益气化瘀清热方治疗肾小球肾炎的作用机制。方法:采用Wersten Blot法检测各组含药血清对大鼠Ms C表达TGF-β1及Smad3蛋白的影响。结果:Wersten印迹结果显示:各组含药血清均能抑制体外培养的Ms C表达TGF-β1及Smad3蛋白,与对照组比较,差异有统计学意义(P<0.05);其中复方组作用最强,与其他含药血清组比较差异有统计学意义(P<0.05),清热组与化瘀组比较无明显差异(P>0.05),但优于益气组,差异有统计学意义(P<0.05)。结论:益气化瘀清热方及其拆方、雷公藤多苷均能抑制体外培养的大鼠Ms C表达TGF-β1及Smad3蛋白的表达。复方组作用明显优于其他组,清热组及化瘀组次之,益气组最弱。     

益气化瘀清热方及其拆方对大鼠肾系膜细胞表达NF-κBp65 mRNA及其蛋白的影响

目的:把益气化瘀清热方拆方成益气、化瘀、清热3组,并与复方组和雷公藤组(TW组)对比,通过体外培养的方法,观察各组含药血清对大鼠肾小球系膜细胞(mesangial cells,MsC)中NF-κBp65 mRNA及蛋白的表达水平高低,进而探讨益气化瘀清热方的作用机制及不同类中药的作用强度。方法:采用RT-PCR法及Wersten Blot法分别检测含药血清对MsC表达NF-κBp65 mRNA及蛋白的作用强度。结果:各组含药血清均能抑制MsC中NF-κBp65 mRNA及其蛋白的表达,化瘀组、TW组作用较强(P0.05);拆方后的益气、化瘀、清热3组比较:化瘀组作用较益气组、清热组明显增强(P0.05)。结论:益气化瘀清热方及其拆方、TW均能抑制体外培养的大鼠MsC表达NF-κBp65mRNA及其蛋白,其中化瘀组、TW组作用较强,益气组较弱。     

辛通畅络法对系膜增生性肾炎大鼠IL-10、IL-13和细胞外基质的影响

目的:观察辛通畅络中药复方肾苏II对系膜增生性肾炎(MsPGN)模型大鼠肾组织白介素10(IL-10)、白介素13(IL-13)及肾小球细胞外基质(ECM)的影响,探讨中医药防治MsPGN的有效途径。方法:采用抗Thy-1系膜增生性肾炎大鼠模型,以中药复方肾苏Ⅱ为治疗药物,贝那普利为对照药物,于治疗6周末,分别观察各组大鼠肾组织IL-10、IL-13和肾小球纤维连接蛋白(FN)、层粘连蛋白(LN)和IV型胶原(ColIV)表达的变化情况。结果:治疗6周末,中药组在改善MsPGN大鼠肾组织IL-10、IL-13表达,减少肾小球FN、LN、ColIV表达量等方面显示疗效优势,且与西药组之间具有显著性差异。结论:以辛通畅络立法的中药复方肾苏Ⅱ,能够减轻肾小球ECM积聚,改善肾小球硬化。     

益气化瘀清热方及其拆方对大鼠肾小球系膜细胞TGF-βRⅠmRNA及其蛋白的影响

目的:观察益气化瘀清热方及其拆方各类含药血清对脂多糖(lipopolysaccharide,LPS)诱导下体外培养大鼠肾小球系膜细胞(primary mesangial cells,Ms C)表达转化生长因子βI型受体(transforming growth factorβ,TGF-β-RI)mRNA及其蛋白的影响。方法:采用RT-PCR法检测各组含药血清对Ms C表达TGF-βRⅠ mRNA的影响;采用Wersten Blot法检测各组含药血清对大鼠MsC表达TGF-βRⅠ蛋白的影响。结果:(1)RT-PCR结果显示:各组含药血清均能抑制体外培养的Ms C表达TGF-βRⅠ mRNA(P<0.01),复方组作用最强,与其他含药血清组比较差异显著(P<0.01),清热组与化瘀组比较无明显差异(P>0.05),但优于益气组(P<0.01)。(2)Wersten印迹结果显示:各组含药血清均能抑制体外培养的Ms C表达TGF-βRⅠ蛋白,复方组作用最强,与其他含药血清组比较差异显著(P<0.01),清热组与化瘀组比较无明显差异(P>0.05),但优于益气组(P<0.01)。结论:益气化瘀清热方及其拆方、雷公藤多苷的含药血清均能抑制体外培养的大鼠Ms C表达TGF-βRⅠmRNA及其蛋白。复方组作用较强,清热组及化瘀组次之,益气组最弱。     

肾络通对大鼠系膜细胞外基质分泌及转化生长因子β1表达的影响

目的: 探讨肾络通药物血清对大鼠系膜细胞外基质不同成分的抑制作用及对转化生长因子β1(TGF-β1)表达的调节作用.方法:以体外培养大鼠肾小球系膜细胞及血清药理学方法为基础,采用酶联免疫吸附试验检测细胞外基质中纤维连接蛋白(FN)、Ⅳ型胶原(ColⅣ)的含量;采用逆转录-多聚酶链反应(RT-PCR)检测TGF-β1 mRNA的表达.结果:细胞外基质FN,ColⅣ的含量与TGF-β1 mRNA的表达呈正相关关系,肾络通对二者均有抑制作用.结论:肾络通能够减少细胞外基质的积聚,抑制TGF-β1的分泌与表达,从而进一步明确了其防治多种肾小球疾病,延缓肾小球硬化的作用机制.     

愈肾颗粒不同药对配伍对肾小球系膜细胞基质金属蛋白酶-2及其抑制剂-2的影响

目的:考察黄芪、太子参(益气摄血组),牡丹皮、丹参(凉血化瘀组),紫草、益母草(解毒化瘀组)3组药对对大鼠肾小球系膜细胞基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶抑制剂-2(TIMP-2)m-RNA表达的影响.方法:应用血清药理学方法,制取中药药对的含药血清.以血管紧张素Ⅱ(AngⅡ)作为刺激因子,培养大鼠肾小球系膜细胞,使其发生增殖.应用反转录多聚酶链反应技术(RT-PCR)观察各组间MMP-2,TIMP-2的基因表达情况.结果:益气摄血组对TIMP-2抑制作用显著,与模型组比较有显著性差异;其他2组虽有抑制趋势,但无统计学意义.3组药对对MMP-2的影响均无统计学意义.结论:黄芪、太子参可通过抑制TIMP-2的基因表达,发挥防治肾小球硬化的作用.     

通肺络补宗气方对肺纤维化大鼠肺功能、MMP9/TIMP1平衡及FN、Col Ⅳ表达的影响

目的:观察通肺络补宗气方对肺纤维化大鼠肺功能、基质金属蛋白酶9(MMP9)/基质金属蛋白酶抑制剂1(TIMP1)平衡及纤维连接蛋白(FN)、Ⅳ型胶原(ColⅣ)的影响。方法:健康雄性SD大鼠96只,按随机数字表法分为空白组、模型组、中药初、中、后期干预组和西药初、中、后期干预组,中药各组给予通肺络补宗气方灌胃,西药各组给予N-乙酰半胱氨酸灌胃,均连续给药90 d。实验第19周检测各组大鼠肺功能相关指标变化以及肺组织中FN、ColⅣ、MMP9和TIMP1蛋白表达水平。结果:与空白组比较,模型大鼠肺功能FVC、Cdyn明显降低,肺组织中FN、ColⅣ、MMP9和TIMP1表达水平明显升高;与模型组比较,中药初、中期干预组大鼠肺功能Cdyn明显升高(P<0.05),中西药各干预组大鼠FN、ColⅣ和TIMP1表达水平明显降低,中药初期干预组大鼠MMP9表达水平明显降低。结论:通肺络补宗气方可调节MMP9/TIMP1失衡,减少FN、ColⅣ的过度沉积,进而改善大鼠肺功能,抑制大鼠肺纤维化的发生发展。     

Isolation and hypoglycemic activity of eleutherans A, B, C, D, E, F, and G: glycans of Eleutherococcus senticosus roots

Intraperitoneal injection of an aqueous extract of the crude drug "shigoka" (Siberian ginseng), Eleutherococcus senticosus roots, remarkably diminished plasma-sugar level in mice. Fractionation of the extract by monitoring the activity yielded seven glycans, eleutherans A, B, C, D, E, F, and G, which exerted marked hypoglycemic effects in normal and alloxan-induced hyperglycemic mice.     

Phytochemistry, Metabolism, and Metabolomics of Ginseng

Ginseng, as a medicinal plant, has been used for thousands of years in China, Korea, and Japan, and the study on ginseng is a hotspot in the research field as evidenced by about 7000 scientific papers in PUBMED. In recent decades, many ginseng studies focused on the metabolism and metabolomics of ginseng or its active ingredients using modern bioanalytical technologies. To date, more than 200 ginsenosides and non-saponin constituents have been isolated and identified. In the past decades, rapid development of analytical technologies has facilitated the advancement of ginseng research in many ways. In this review, we focus on the advances of ginseng research in chemistry, pharmacology, and metabolomics. We also provide the comments on the significance as well as challenges of metabolomics-based ginseng studies.     

Correlation of Metabolism, Metabolomics, and Metabonomics

<正>In this issue,CHM published two reviews on drug metabolism of Chinese herbal medicines.Three key words have been found,they are metabolism,metabolomics,and metabonomics.As we known,drug metabolism is the biochemical modification of pharmaceutical substances respectively by living organisms through specialized enzymatic systems,the rate of metabolism determines the duration and intensity of pharmacological responses     

Isolation and structure of homotemsirolimuses A, B, and C

Homotemsirolimuses A, B, and C (2a, 2b, 2c) were found to be minor components of a temsirolimus preparation made from rapamycin. These three temsirolimus analogues are derived from the corresponding rapamycin analogues, homorapamycins A, B, and C (1a, 1b, 1c) produced by the strain Streptomyces hygroscopicus. The structures of homotemsirolimuses A, B, and C were determined by spectroscopic methods. These compounds were tested for mTOR kinase inhibition and in two proliferation assays using LNCap prostate and MDA468 breast cancer cells. The results suggested that the mTOR inhibition and antiproliferation potencies for 2a, 2b, and 2c are comparable to those of rapamycin (1) and temsirolimus (2).     

Antimalarial activity of physalins B, D, F, and G

The antimalarial activities of physalins B, D, F, and G (1-4), isolated from Physalis angulata, were investigated. In silico analysis using the similarity ensemble approach (SEA) database predicted the antimalarial activity of each of these compounds, which were shown using an in vitro assay against Plasmodium falciparum. However, treatment of P. berghei-infected mice with 3 increased parasitemia levels and mortality, whereas treatment with 2 was protective, causing a parasitemia reduction and a delay in mortality in P. berghei-infected mice. The exacerbation of in vivo infection by treatment with 3 is probably due to its potent immunosuppressive activity, which is not evident for 2.     

Antimicrobial, anti-inflammatory, antiparasitic, and cytotoxic activities of Galium mexicanum

Ethnopharmacological relevance

To study the potential benefit of the traditional Mexican medicinal plant Galium mexicanum Kunth (Rubiaceae). Hexane, chloroform, and methanol extracts as well as various fractions from these extracts were tested to determine antibacterial, antifungal, antiparasitic or anti-inflammatory activities in vitro.

Materials and methods

Aerial parts of the plant were extracted with various solvents and fractionated accordingly. Their antibacterial and antifungal activities were assessed on nine bacterial and four fungal strains. Leishmania donovani was used as a protozoan strain for antiparasitic activity. The anti-inflammatory activity of the compounds was investigated by measuring the secretion of interleukin-6 when macrophages were exposed to lipopolysaccharide.

Results

Various extracts and fractions obtained from this plant exhibit antibacterial, antifungal, antiparasitic, and anti-inflammatory activities. Of special interest was the hexane fraction HE 14b, which show antibacterial (ranging between 67 and 666 μg/ml) and antifungal (at concentrations of 333 μg/ml) activities. Also the hexane fraction HE 5 exhibited antiparasitic activity (at concentrations of 260 μg/ml), whereas the methanol fraction ME 13-15 showed a potent anti-inflammatory activity when compared to dexamethasone. Chemical analyses of the chloroform extract show the presence of triterpenes, saponins, flavonoids, sesquiterpene lactones, and glucosides, but no tannins were detected in the assayed extract.

Conclusions

The benefit of Galium mexicanum as a traditional medicinal plant was confirmed using antibacterial and antifungal assays in vitro. We also report for the first time, and to the best of our knowledge, antiparasitic and anti-inflammatory activities of this plant.     

酸柏栀油软胶囊对小鼠学习记忆及脑中NO、Ach的影响

目的:观察酸柏栀油软胶囊对小鼠的促学习记忆作用并初步探讨其机制。方法:采用Morris水迷宫法观察酸柏栀油软胶囊对小鼠的学习记忆影响,并测定小鼠脑内NOS、ChaE、AChE的含量。结果:酸柏栀油软胶囊1.25～5 ml/kg能缩短小鼠登台潜伏期,增加穿越原平台次数,以中剂量作用最强;且登台潜伏期随训练时间的延长,各组作用均逐渐增强,d20的作用尤为明显。酸柏栀油软胶囊尚能增加小鼠脑内NOS、ChaE活性,降低AChE活性,也以中剂量作用为佳。结论:酸柏栀油软胶囊对小鼠学习记忆有促进作用,该作用可能与其富含不饱和脂肪酸,增加脑内NO、Ach的含量有关。     

何首乌中总黄酮与微量元素含量分析及其药效机理研究

目的分析中药何首乌中总黄酮与微量元素Mg，Fe，Mn，Cu，Zn的含量。方法紫外分光光度法测定何首乌中总黄酮的含量；原子吸收分光光度法测定Mg，Fe，Mn，Cu，Zn的含量。结果总黄酮的含量27．44mg／g；Mg：952．4801&#177;10．5543μg／g；Fe：7196．7256&#177;98．8101μg；Mn：431．0929&#177;5．5698μg／g；Cu：5．5438&#177;0．1513μg；Zn：86.7915&#177;6．4781μg／g。结论实验结果为探讨中药何首乌中黄酮类化合物与微量元素的关系及研究何首乌中微量元素与药物的功效关系提供了有用的方法和依据。     

实验探讨生大黄、清半夏、常山的升降浮沉药性

目的:通过动物实验探讨生大黄、清半夏、常山的升降浮沉药性,为中药的升降沉浮药性研究提供新的思路和方法.方法:运用小鼠肠推进及肠容积实验比较生大黄、清半夏、常山水煎液对消化系统的影响;运用正常大鼠血压及血清NO含量实验和小鼠微循环实验比较其对血液循环系统的影响;运用小鼠睡眠时间和自主活动实验比较其对中枢神经的影响.从与气机运动相对应的关系讨论药物的升降浮沉.结果:生大黄能明显促进小鼠小肠的排空,对血液循环系统表现出促进作用;对中枢神经有一定的兴奋作用.清半夏对消化系统的影响不明显,对血液循环系统表现出促进作用;对中枢神经具有明显的抑制作用.常山对消化系统的活动有明显的抑制作用,对血液循环系统表现出促进作用,对中枢神经系统效果不明显.结论:综合三药对各个系统的影响,从与气机运动相对应的关系,常山表现出向上向外的趋势,为升浮药;生大黄、清半夏表现出向下向内的趋势,为沉降药.