前胡香豆素B和前胡香豆素C的分离和鉴定

从中药白花前胡(Peucedanum praeruptorum)根中分离和鉴定了5个化合物,经理化常数测定,波谱数据解析及化学反应,分别鉴定为3′-angeloyloxykhellactone(Ⅸ)、前胡香豆素B(Ⅹ)、前胡香豆素C(Ⅺ)、Pd-Ⅲ(ⅩⅢ)和peucedanocoumarin Ⅲ(ⅩⅤ)。其中化合物Ⅹ和Ⅺ为两个新化合物,通过和凯林内酯的化学沟通确定了其绝对构型。其化学结构分别为3′(S)-乙酰氧基-4′(S)-羟基-3′,4′-二氢邪蒿内酯(Ⅹ)和3′(S)-羟基-4′(S)-乙酰氧基-3′,4′-二氢邪蒿内酯(Ⅺ)。Ⅸ为首次报道自天然物中分得。     

白花前胡中白花前胡甙和Pd-C-I的分离和鉴定

从白花前胡(Peucedanum,praeruptorum)根中分得7个化合物,经化学方法和光谱分析分别鉴定为Pd-C-I(I),白花前胡甙(II),香草酸(III),没食子酸(IV),nodakenin(V),rutarin(VI)和isorutarin(VII)。II为新化合物,其化学结构为4-O-β-D-吡喃葡萄糖基-3-甲氧基苯丙酮,命名为白花前胡甙。I为首次从白花前胡中分得的线型二氢吡喃香豆素类化合物,这对前胡属植物化学分类学有一定意义。还利用2DNMR纠正了文献中关于化合物I和VII的个别碳信号归属的错误。     

紫花前胡化学成分的研究

目的研究中药紫花前胡［Peucedanum decursivum(Miq.)Maxim］根的化学成分。方法用硅胶柱色谱和制备型高效液相色谱进行分离纯化,用光谱分析和化学方法鉴定其结构。结果从紫花前胡根中分得7个线型吡喃香豆素类化合物,其结构分别鉴定为3′(S)-hydroxy-4′(R)-angeloyloxy-3′,4′-dihydroxanthyletin(1);3′(S)-acetoxy-4′(R)-hydroxy-3′,4′-dihydroxanthyletin(2);3′(S)-acetoxy-4′(R)-angeloyloxy-3′,4′-dihydroxanthyletin(3);Pd-C-IV(4);Pd-C-II(5);(+)-3′S-Decursinol(6);(+)-trans-Decursidinol(7)。结论化合物1和2为新化合物,分别命名为紫花前胡素D和紫花前胡素F;6和7为首次从该植物中分得。     

前胡香豆素A的分离和结构鉴定

从中药白花前胡(Peucedanum praeruptorum Dunn)根中分离得到7个化合物,经理化常数和波谱数据的测定以及化学反应,鉴定为补骨脂素(Ⅱ)、5-甲氧基补骨脂素(Ⅲ)、8-甲氧基补骨脂素(Ⅳ)、北美芹素(Ⅴ)、peucedanocoumarin Ⅱ(Ⅵ)、β-谷甾醇(Ⅶ)和前胡香豆素A(Ⅷ)。Ⅷ为一新化合物,通过和凯林内酯的化学沟通确定了其绝对构型,化学结构为3′(R)-羟基-4′(E)-惕各酰氧基-3′,4′-二氢邪蒿内酯。Ⅱ～Ⅳ和Ⅶ为首次从白花前胡中分离得到。     

白花前胡中前胡香豆素D和前胡香豆素E的分离和鉴定

从中药白花前胡(Peucedanum Praeruptorum Dunn)根中分到5个化合物,经理化常数、波谱数据及化学反应分别鉴定为前胡香豆素D(I),Pd-Ib(II),前胡香豆素E(III),nodakenetin(IV)和scopoletin(V)。其中化合物I和III为两个新化合物,与巳知化合物凯林内酯的化学沟通确定了其绝对构型,其化学结构分别为3'(S),4'(S)-二乙酰氧基-3',4'-二氢邪蒿内酯(I)和3'(R)-惕各酰氧基-4'-酮基-3',4'-二氢邪蒿内酯(III)。化合物IV和V为首次从该植物中分离得到。通过DEPT,¹H-¹HCOSY和¹³C-¹HCOSY等实验归属了II的碳氢信号。     

白花前胡丙素C-3′和C-4′反式结构类似物的半合成白花前胡丙素C-3′和C-4′反式结构类似物的半合成

目的对白花前胡丙素［(+)-praeruptorin A］进行结构修饰,半合成C-3′和C-4′反式结构类似物,寻找活性化合物。方法首先从白花前胡(Peucedanum praeruptorum)根中分离得到白花前胡丙素,从白花前胡丙素出发,运用碱水解及各种酰化反应,半合成各种结构修饰产物。结果首次合成了17个白花前胡丙素C-3′和C-4′反式结构类似物,通过IR,¹HNMR,MS等方法确定它们的结构。结论17个化合物均为新化合物,其中一些新化合物有显著的钙离子拮抗活性,首次证明C-3′和C-4′反式结构的这类化合物同样具有活性。     

基于UPLC法快速测定前胡配方颗粒中指标性成分

目的 建立超高效液相法(UPLC)对前胡配方颗粒中白花前胡甲素、白花前胡乙素和白花前胡素E同时快速定量分析的方法。方法 采用Acquity UPLC BEH C₁₈色谱柱(50 mm×2.1 mm, 1.7μm),以甲醇-水为流动相,梯度洗脱,体积流量0.4 mL·min^-1,在321 nm波长处进行检测,柱温25℃,进样量2.0μL。结果 前胡配方颗粒中3种有效成分在考察线性范围内线性关系良好,白花前胡甲素、白花前胡乙素、白花前胡素E的线性范围分别为1.870～18.70μg·mL^-1(r=0.9998)、0.2075～2.075μg·mL^-1(r=0.9998)、0.2220～2.220μg·mL^-1(r=0.9997),加样回收率均在98.85%～99.76%,RSD均小于2.0%。结论 该方法简便,准确,快速,重复性好,可用于前胡配方颗粒的快速质量控制,并为将来该配方颗粒的质量标准提升提供参考。     

南岭前胡素A的结构鉴定

从前胡属新种植物南岭前胡(Peucedanum longshengense Shan et Sheh)根中首次分离得到2个单体化合物,经理化常数、波谱数据解析,分别鉴定为南岭前胡素A(I)和甘露醇(II)。晶I为一新化合物,通过和凯林内酯的化学沟通确定其绝对构型,化学结构为(-)-3′(S)-乙酰氧基-4′(S)-当归酰氧基-3′,4′-二氢邪蒿内酯。     

白花前胡丙素的结构修饰研究

目的对白花前胡丙素［(+)-praeruptorin A］进行结构修饰,寻找活性化合物。方法首先从白花前胡(Peucedanum praeruptorum)根中分离得到白花前胡丙素,从白花前胡丙素出发,用碱水解及各种酰化反应,半合成各种结构修饰产物。结果得到18个(2～19)凯林内酯类化合物,通过IR,¹HNMR和MS等方法确定其结构。结论其中14个(5～18)为新化合物,这些新化合物均有不同程度的钙离子拮抗活性,但作用强度均较白花前胡丙素弱。     

白花前胡中白花前胡甙和Pd－C－I的分离和鉴定

从白花前胡（Ｐｅｕｃｅｄａｎｕｍ，ｐｒａｅｒｕｐｔｏｒｕｍ）根中分得７个化合物，经化学方法和光谱分析分别鉴定为Ｐｄ－Ｃ－Ｉ（Ｉ），白花前胡甙（ＩＩ），香草酸（ＩＩＩ），没食子酸（ＩＶ），ｎｏｄａｋｅｎｉｎ（Ｖ），ｒｕｔａｒｉｎ（ＶＩ）和ｉｓｏｒｕｔａｒｉｎ（ＶＩＩ）。ＩＩ为新化合物，其化学结构为４－Ｏ－β－Ｄ－吡喃葡萄糖基－３－甲氧基苯丙酮，命名为白花前胡甙。Ｉ为首次从白花前胡中分得的线型二氢吡喃香豆素类化合物，这对前胡属植物化学分类学有一定意义。还利用２ＤＮＭＲ纠正了文献中关于化合物Ｉ和ＶＩＩ的个别碳信号归属的错误。     

RP-HPLC法测定清肺抑火丸中白花前胡甲素的含量

目的:建立以反相高效液相色谱法测定清肺抑火丸中白花前胡甲素含量的方法。方法:色谱柱为Diamonsil-C18(250mm×4.6mm,5μm),流动相为甲醇-水(81:19),检测波长为322nm。结果:白花前胡甲素的检测浓度在4.65～23.25μg·mL-1范围内与峰面积积分值呈良好的线性关系(r=0.9999);平均回收率为100.5%,RSD=2.35%(n=6)。结论:本方法分离效果好、灵敏、准确,可用于清肺抑火丸中白花前胡甲素的含量测定。     

前胡丙素对肾性高血压左室肥厚大鼠心功能、左室顺应性及心肌胶原含量的影响

观察前胡丙素对肾性高血压左室肥厚(LVH)大鼠心功能、左室顺应性及心肌胶原含量的影响。用两肾一夹肾性高血压动物模型,ig前胡丙素(Pra-C)9周。结果,与LVH组相比,Pra-C组的CF/HWW及CO/HWW分别增加31.3%和28.9%;LVSP和-dp/dt_max负值分别增加16.7%和27.8%;LVEDP和T值分别降低34.9%和36.5%;P-V曲线接近正常组水平;左室肌羟脯氨酸降低23.8%。提示Pra-C可提高LVH大鼠心脏收缩及舒张功能,改善心肌顺应性。     

前胡丙素与硝苯啶对大鼠工作心脏缺血再灌注损伤的保护作用

大鼠ip前胡丙素(Pra-C 15 mg/kg,bid×3d)和硝苯啶(Nif 60μg/kg,bid×3d),使离体缺血再灌注工作心脏的收缩(AP,LVSP,+dP/dt_max)舒张(-dP/dt_max LVEDP和T值)性能在35min时得到改善,尤以舒张性能改善明显,并能促进CO,CF,SV及HR恢复,改善心脏工作效率,减少CK释放和心肌线粒体钙含量,表明Pra-C和Nif对心肌缺血都有保护作用,Pra-C的效应与Nif相近。     

EFFECTS OF CHROMAN DERIVATIVES ON PLATELET AGGREGATION INDUCED BY SOME AGGREGATING AGENTS IN RABBITS

1. We synthesized 10 chroman derivatives (CD-1 to CD-10) derived from khellactone, including praeruptorin A and praeruptorin B and examined the effects of these compounds on rabbit platelet aggregation. 2. These compounds exhibited an inhibitory effect on platelet-activating factor (PAF)-induced platelet aggregation and their effects were more potent on PAF-induced platelet aggregation than on adenosine triphosphate (ADP)-, arachidonate (AA)- or collagen-induced platelet aggregation. In particular, (±)-cis-5-methoxy-6-methoxycarbonyl-2,2-dimethyl-3,4-ditiglyloxychro-man (CD-6), (±)-cis-5-methoxy-6-(2-methoxycarbonylethenyi)-2,2-dimethyl-3,4-ditiglyloxychroman (CD-8), (±)-cis-3,4-diacetoxy-5-methoxy-2,2-dimethyl-6-propylchroman (CD-9) and (±)-cis-5-methoxy-2,2-dimethyl-6-propyl-3,4-ditiglyloxy-chroman (CD-10) showed a moderate inhibition of PAF-induced platelet aggregation. 3. From these findings, it is suggested that compounds with potent PAF antagonist activities have the following features: (i) a tiglyloxy moiety is required at the 3 and 4 positions; and (ii) the methoxy moiety is also required at the 5 position of chroman skeleton in khellactone.     

Effects of praeruptorin C and E isolated from 'Qian-Hu' on swine coronary artery and guinea-pig atria

Praeruptorin C and E isolated from Peucedanum praeruptorum Dunn. decreased the maximum contractile effect of Ca2+ in potassium-depolarized swine coronary strips and shifted the concentration-response curve to the right in a non-parallel manner. The calcium antagonistic activity of praeruptorin C and E expressed as pD'2 value was 5.7 and 5.2, respectively. Nifedipine, with a pD'2 value of 6.88, was used as a known calcium antagonistic drug to compare the potency of the drugs studied. The relaxation induced by praeruptorin C was concentration-dependent and the IC50 value was 79 microM. Praeruptorin C also reduced the maximum contractile response and shifted the concentration-response curve for calcium to the right in a non-parallel manner in potassium-depolarized guinea-pig left atria (pD'2 = 5.52) but its potency was much less than that of nifedipine (pD'2 = 7.19). The results suggest that praeruptorin C and E relaxed swine coronary artery and decreased contractility in guinea-pig left atria. These effects are similar in many respects to those displayed by drugs that have calcium entry blocking activity.     

3'-O, 4'-O-aromatic acyl substituted 7,8-pyranocoumarins: a new class of P-glycoprotein modulators

Objectives P‐glycoprotein (Pgp) overexpression in tumour cells leads to multidrug resistance (MDR) and causes failure in cancer chemotherapy. We have previously identified (±)‐praeruptorin A (PA) as a potential lead compound for Pgp modulators. In this study we investigated the MDR‐reversing activities of PA derivatives. Methods Series 7,8‐pyranocoumarins with various C‐3′ and C‐4′ side chains had been semi‐synthesized and their MDR‐reversing activity was investigated in Pgp‐overexpressing MDR tumour cell line HepG2/Dox and in a KB V1 xenograft animal model. Key findings All 7,8‐pyranocoumarins exhibited equal or higher activity in modulating Pgp. DCK ( 12 ), DMDCK ( 15 ), 16 , 21 , 23 and 24 at 4 µm achieved 91%～99% decrease in IC50 value (concentration inhibiting cell growth by 50%) of anticancer agents vinblastine, doxorubicin, puromycin and paclitaxel, and were more active than others. DMDCK also remarkably enhanced the growth inhibitory effect of paclitaxel on KB V1 xenografts (P < 0.05), showing a potency required for clinical usage. Mechanistic studies suggested that these 7,8‐pyranocoumarins might reverse Pgp‐MDR through directly binding to substrate binding site(s) or allosteric site(s) on Pgp therefore impairing Pgp‐mediated drug transport. Conclusions Results from the study suggested that 3′‐O, 4′‐O‐aromatic acyl substituted 7,8‐pyranocoumarins could serve as a new class of Pgp modulator. Acyls play an important role in maintaining and enhancing the Pgp‐modulating ability of pyranocoumarins. 3,4‐Dimethoxyl substituted aromatic acyls, bearing a methoxy that might interact with Pgp as hydrogen bond accepter, were shown to be the most potent for reversing MDR.     

苯噻唑力复霉素作用机理的初步研究

本文报告苯噻唑力复霉素对细菌生物大分子合成及超微结构的影响。该药可明显抑制³H-尿嘧啶核苷掺入金黄色葡萄球菌209 p和大肠杆菌2281的RNA;对²H-亮氨酸掺入细菌蛋白质仅有轻微抑制;对³H-胸嘧啶核苷掺入细菌DNA无抑制作用。说明其作用机理主要是抑制细菌RNA合成。掺入试验还表明金黄色葡萄球菌对苯噻唑力复霉素有比大肠杆菌更高的敏感性。10倍于MIC浓度的苯噻唑力复霉素能使上述两种细菌超微结构明显改变。胞质失去完整结构,出现空泡,核糖体消失,但胞壁仍保存。     

THE EFFECT OF HYPERTENSIVE EPISODES AND CARDIAC HYPERTROPHY ON THE CANINE CARDIAC BAROREFLEX

1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevation. 2. Five mongrel dogs were exposed to transient blood pressure elevation of between 20 and 30 mmHg, through hindlimb compression using a pneumatic pressure suit, for 7 h per day, 6 days per week for 6 weeks. Resting blood pressure was not altered by the 6 week hindlimb compression intervention. 3. Echocardiographically determined LV mass (mean ± s.e.m.) was 116.0 ± 7.4 g prior to hindlimb compression (baseline) and elevated to 125.4 ± 8.1 g (P= 0.003) after 6 weeks of compression. A reduction in the early (E) to late (A) transmitral diastolic flow ratio (E/A) from 1.80 ± 0.06 at baseline to 1.54 ± 0.09 (P = 0.037) after the 6 week intervention suggested that cardiac compliance was reduced. 4. The maximum gain of the MAP-HR reflex, studied using the ‘steady-state’ drug technique, when blood pressure was normal, showed a trend for reduction from 3.85 ± 0.43 beats/min per mmHg at baseline to 3.10 ± 0.45 beats/min per mmHg (P= 0.067) after 6 weeks of compression. This gain reduction became significant after β-adrenoceptor blockade with propranolol (3.13 ± 0.55 vs 2.32 ± 0.25 beats/min per mmHg; P= 0.039). Covariant analysis showed a significant inverse correlation between LV mass and maximum gain (r= 0.96; P<0.001) during the 6 week compression period. 5. The MAP-HR reflex changes in this model mimic those present in hypertension and implicate cardiac hypertrophy as one possible mediator.     

国产檀香油化学成分和五个新化合物的初步结构研究

檀香(Santalum album L.)为檀香科(Santalaceae)植物,主产于印度、印尼和马来西亚等地。檀香心材为常用中药,其挥发油檀香油广用于日用化学品工业,檀香木为高级雕刻材料。过去,我国所需的檀香木和檀香油均由国外进口。50年代末,我国一些单位相继引种,我所的海南和云南两个分所亦进行引种。檀香木含挥发油量最高可达10%,通常为2.5～5%,云     

正交试验优选防感颗粒的提取工艺

目的确立防感颗粒的最佳提取工艺。方法应用正交试验和HPLC,以防感颗粒中R,S-告依春、白花前胡甲素、苦杏仁苷及甘草苷4种活性成分含量为指标,采用多指标综合评分法,确定防感颗粒的提取工艺。结果防感颗粒最佳提取工艺为:药材加8倍量水,煎煮3次,每次1.5 h,乙醇浓度为60%。结论优选出的工艺稳定可靠,可用于防感颗粒的提取。