甘草叶中甘草宁P-3′-甲醚的分离和鉴定

Two flavonoids were isolated from the leaves of Glycyrrhiza uralensis Fisch (Licorice, Leguminosae). On the basis of physico-chemical properties and spectroscopy (UV, ¹HNMR and MS), a new compound was elucidated as 3,5,7,4′-tetrahydroxy-3′-methoxy- 6-isoprenyl flavone (gancaonin P-3′-methylether) and another known compound was identified as 8-C-prenyleriodictyol.     

Δ16-娠烯-3β-乙酰氧基-11:20-二酮的极谱测定

A simple and rapid method for the determination of △~(16)—pregnene-3β—acetoxy — 11:20 — dione has been worked out. In an aqueous 40% iso-propanol solution of 0.1N NH₄Cl, this steroid gave a double polarographic wave which could be used for its determination. The current was measured at —1.50 v. vs. S.C.E. and was proportional to the concentration in the range of 36 to 180/μg/ml. From the experimental results, the diffusion current constant I and the diffusion coefficient D have been calculated to be 1.30 and 1.15 ×10^-6 cm²/sec. respectively. This method has been applied to the analysis of a sample; the result agreed with that obtained by the spectrophotometric method.     

血吸虫病化学治疗的研究——ⅩⅩⅩⅣ.α-氯-β-(5-硝基-2-呋喃)丙烯酰胺类及其乙烯噁二唑类衍生物的合成

Synthesis of 35 new compounds of α-chloro-β-(5-nitro-2-furyl) acrylamides and 5-[α-chloro-β-(5-nitro-2-furyl ) vinyl]-oxadiazoles by known methods are reported. In preliminary test in mice 10 compounds were found to possess pronounced activity against Schistosomiasis japonica. Among these Ⅰ₁₂, Ⅰ₁₃, Ⅰ₁₄, Ⅰ₂₀, Ⅱ₁ and Ⅱ₈ were shown to be the most effective.     

黄甘草异黄酮成分的研究

从黄甘草(Glycyrrhiza eurycarpa P.C.Li)根及根茎中分得五个异黄酮化合物,根据理化性质及光谱(UV,MS,¹HNMR,¹³CNMR,NOE,HMBC)数据分析,化合物I的结构推定为7,2′,4′-三羟基-3′-异戊烯基异黄酮,为一新化合物,命名为黄甘草异黄酮A(eurycarpinA)。化合物I的结构推定为7,2′-二羟基-(2″,3″∶4′,3′)-6″,6″-二甲基吡喃异黄酮,为一新的天然产物,命名为黄甘草异黄酮B(eurycarpinB)。其余化合物分别鉴定为 licoisoflavone A(III),毛蕊异黄酮(calycosin,IV)和芒柄花素(formononetin,V)。化合物II～V均为首次从本植物中得到。     

Elucidation of individual cytochrome P450 enzymes involved in the metabolism of clozapine

The atypical antipsychotic clozapine has been reported to be metabolised mainly to its N-oxide and N-demethylated products. In the present study, individual recombinant cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) enzymes were used to elucidate which enzymes are responsible for these metabolic con-versions. In vitro metabolism of clozapine was investigated using human CYP1A1, CYP1A2, CYP2C8, CYP2EI, CYP2C9-arg₁₄₄, CYP2C9-cys₁₄₄, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and FMO3 supplemented with an NADPH generating system. Clozapine and its N-oxidation and N-demethylation metabolites were determined by an HPLC method with a Hypersil CN column and a UV detector. Of the enzymes investigated, CYP1A2, CYP3A4, CYP2D6, CYP2C8, CYP2C19 and, to a lesser extent, CYP2C9-cys, CYP2C9-arg and CYP3A5 were apparently involved in N-demethylation, while CYP1A2, CYP3A4, FMO3 and, to a lesser extent, CYP2C8, CYP2C19 and CYP3A5 were found to catalyse the formation of clozapine N-oxide. A bank of 16 human liver microsome preparations was investigated for ability to catalyze the production of clozapine N-oxide and N-desmethylclozapine. Attempts were made to correlate the rates of formation of these metabolites of clozapine to previously determined catalytic activities of CYP1A2, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. At a clozapine concentration of 20 μM, the rate of formation of clozapine N-oxide showed significant correlations with activities of CYP3A4 (P<0.01) and CYP1A2 (P<0.05). The formation of N-desmethylclozapine exhibited significant correlations with CYP1A2 (P<0.01) and CYP3A4 (P<0.01). Similar correlations were observed when the clozapine concentration was increased to 300 μM except that the formation of clozapine N-oxide no longer correlated with CYP1A2 activity. It can be seen from these results that although some recombinant enzymes individually are capable of metabolising clozapine, the activities of several of these enzymes did not correlate with clozapine metabolism when mixtures of the enzymes are used. By combining the results of the current study and those reported in the literature, it is proposed that CYP3A4 and FMO3 are primarily responsible for the production of clozapine N-oxide, and CYP3A4 and CYP1A2 are primarily responsible for the formation of N-desmethylclozapine. The present study demonstrates the importance of the use of multiple techniques for the elucidation of the enzymes involved in the metabolism of certain drugs. Received: 2 December 1997 / Accepted: 15 June 1998     

抗高血压药物2-亚氨基-3-(β-羟基苯乙基)-噻唑烷衍生物的合成

2-Imino-3-(β-hydroxyphenethyl)thiazolidine showed hypotensive activity. In order to find more active derivatives, a series of compounds has been synthesized.In preliminary screening tests, Compounds (Ⅱ-2) and (Ⅳ-1) showed considerable hypotensive effect.     

Ontogeny of adenosine receptors in the longitudinal muscle and muscularis mucosae of the rat distal colon

The development of adenosine A₁ and A_2B receptors on the longitudinal muscle and muscularis mucosae of the neonatal rat distal colon has been investigated using homogenate binding, quantitative autoradiography and functional studies. In homogenate binding studies 1,3-[³H]-dipropyl-8-cyclopentylxanthine ([³H]DPCPX) bound with high affinity to A₁ receptors in the muscularis mucosae and intact colon from rats aged 10, 15, 20, 25 and 30 days. The affinity of [³H]DPCPX was similar to that in the adult at all ages, but the density of binding sites was higher in the neonatal tissues. Quantitative autoradiography showed a higher density of [³H]DPCPX binding sites in the longitudinal muscle than in the muscularis mucosae at all ages studied (day 10 to adult), and this binding was concentration-dependently displaced by N ⁶-cyclopentyladenosine (CPA). In functional studies the longitudinal muscle relaxed in response to 5’-N-ethylcarboxamidoadenosine (NECA) and CPA at all ages studied (15–30 days), NECA being more potent than CPA. The potency of NECA remained constant and it was antagonised by 1 μM DPCPX at all ages with pA ₂-values consistent with activation of A₂ receptors. The inactivity of 2-[p-(carboxyethyl)-phenylethylamino]-5’-N-ethylcarbox-amidoadenosine (CGS 21680) indicated that the A₂ receptors were of the A_2B subtype. The muscularis mucosae contracted in response to CPA at all ages studied (day 15 to adult) and the antagonism by DPCPX (10 nM) were consistent with activation of A₁ receptors. In conclusion, binding, autoradiographic and functional studies identified A₁ receptors on the rat colon muscularis mucosae at all ages studied. However, while binding and autoradiographic localisation showed the presence of A₁ receptors in the longitudinal muscle at all ages studied, functional data only revealed the presence of A_2B receptors. Received: 3 July 1998 / Accepted: 25 November 1998     

槲寄生化学成分的研究——Ⅷ.2,3-丁二醇单葡萄糖甙的分离和结构

From the ethanol extract of Viscum coloratum (Kom.) Nakai , a giucoside ofaliphatic diol and three other glucosides were isolated. Based on chemical and spectroscopic analysis,the structures have been elucidated as 2-β-D- glucosyl-3- methylpropanol (Ⅷ), syringin (Ⅸ),eleatheroside E(Ⅹ) and syringenin-4'-O-D-apiosylglucoside (Ⅺ). Ⅷ is a new glucoside of aliphaticdiol and named 3-β-D-glucopyranosyloxy-butanol-2. Three other compounds (Ⅸ～-Ⅺ) were foundfor the first time in this plant.     

Manipulations of mu-opioid and nicotinic cholinergic receptors in the pontine tegmental region alter cocaine self-administration in rats

Rationale: The pedunculopontine tegmental nucleus (PPTg) has been implicated in drug reward, particularly in the development of dependence. However, little is known of the receptor systems within this nucleus which might be involved. Furthermore, some research suggests that the PPTg may also be part of the neuronal circuitry involved in established drug-taking behavior. Objective: The objective of these experiments was to examine the role of mu-opioid and nicotinic cholinergic mechanisms in the PPTg in cocaine self-administration. Methods: Microinfusions of mu-opioid and nicotinic receptor selective compounds were made into the PPTg of rats trained to self-administer cocaine intravenously, in the vicinity of cholinergic cells which are known to project to the midbrain dopamine neurons of the ventral tegmental area (VTA). Results: The mu-opioid selective agonist DAMGO, tested at doses of 0, 0.05 and 0.5 μg, produced a dose-related reduction in the number of cocaine infusions obtained during the 1-h self-administration sessions. The mu-selective antagonist CTOP (0–2 μg) and nicotine (0–10 μg) did not produce significant changes in cocaine self-administration. Microinfusions of the nicotinic antagonist dihydro-β-erythroidine (0–30 μg) produced a small but significant increase in cocaine-maintained responding. Conclusions: These data show that mu-opioid mechanisms in the PPTg can influence cocaine self-administration markedly. Moreover, the data demonstrate that PPTg circuitry can influence drug reward in already-established drug-reinforced behavior, as well as during the development of dependence (as shown by previous research). Received: 30 November 1998 / Final version: 25 March 1999     

广西境内不同产区土茯苓中落新妇苷的含量测定

目的 测定广西境内不同产区土茯苓中落新妇苷的含量.方法 采用高效液相色谱法,Zorbax SB-C18柱(250 mm×4.6 mm,5μm),流动相为甲醇-0.1%冰醋酸溶液(34:66),检测波长为291 nm.结果 不同产区土茯苓中落新妇苷含量差异较大,但都符合2010年版<中国药典(一部)>要求.结论 文中所作试验为有效开发利用广西地区的土茯苓提供了科学依据.     

Antiinflammatory constituents from the roots of smilax bockii warb.

From 70% ethanol extract of the roots of Smilax bockii warb., seven flavonoids, kaempferol (1), kaempferol-7-O-beta-D-glucopyranoside (2), quercetin (3), isorhamnetin (4), (+)-dihydro-kaempferol (5), engeletin (6), isoengeletin (7), and n-butyl-beta-D-fructopyranoside (8), caffeic acid n-butyl ester (9) were isolated and identified by means of chemical and spectroscopic. Compounds 2, 4, and 6-9 were isolated for the first time from the roots of S. bockii and compounds 2, 8, and 9 were firstly isolated from the genus Smilax. In addition, using the SEAP (Secreted alkaline phosphatase) assay system, we investigated the in vitro anti-inflammatory activity of the 70% ethanol extract of the roots of S. bockii, which showed moderate activity in inhibiting TNF-alpha-induced NF-kappaB activation with an IC50 value of 166.6 microg/mL.     

A new flavanone isolated from rhizoma smilacis glabrae and the structural requirements of its derivatives for preventing immunological hepatocyte damage

From the rhizome of Smilax glabra Roxb., a new flavanone was isolated and named as smitilbin (1), together with 6 known compounds, engeletin (2), astilbin (3), dihydroquercetin (4), eurryphin (5), resveratrol (6), and 5-O-caffeoylshikimic acid (7). These compounds were applied to the assay of liver nonparenchymal cells (NPC) against hepatocytes (HC) isolated from mice with an immunological liver injury. Against the NPC-caused elevation of ALT (alanine transminase) in culture supernatant from HC, the pretreatment of NPC with flavanoids (1-3) dose-dependently blocked the ALT release while 4, the aglycone of 3, did not. The chromone 5 showed a much stronger inhibition. Compound 6 also showed the activity. However, 1-7 did not show any suppression of NPC or CCl4-induced ALT release when they were used to pretreat HC. These results suggest that compounds 1-3, 5, and 6 could protect the hepatocyte damage from NPC through selectively producing the dysfunction of NPC with an essential requirement of rhamnose, and the chromone part in their structures may be critical for exhibiting the activity rather than through protecting the hepatocyte membranes.     

金雀异黄素4′-二氟甲醚化衍生物的合成

目的 合成金雀异黄素4′-二氟甲醚化衍生物。方法 金雀异黄素与HCF2Cl、NaOH在水和二氧六环的混合液中发生二氟甲醚化反应，生成7，4′-二-二氟甲氧基-5-羟基异黄酮（2）、7-二氟甲氧基-5，4′_二羟基异黄酮（3）和4′-二氟甲氧基-5，7-二羟基异黄酮（4），再经甲醚化反应得到7-二氟甲氧基-5，4′-二甲氧基异黄酮（5）和4′-二氟甲氧基-5，7-二甲氧基异黄酮（6）。结果 化合物的结构经MS、^1H-NMR、^13C-NMR、^19F-NMR等进行了确证，化合物（4）和（6）为首次合成的新化舍物。结论 为金雀异黄素4′-二氟甲醚化衍生物的合成提供了实验基础。     

土茯苓水提物对高尿酸血症模型小鼠血清尿酸和甘油三酯、胆固醇的影响

目的:研究土茯苓水提物对高尿酸血症模型小鼠血清尿酸(UA)和甘油三酯(TG)、胆固醇的影响。方法:实验分为空白(等容蒸馏水)、模型(等容蒸馏水)、土茯苓水提物(10g(生药)·kg-1)、别嘌呤醇(40mg·kg-1)组。ig酵母30g·kg-11周复制模型,复制模型成功后分别ig相应药物,7d后检测各组大鼠血中胆固醇、TG、UA含量和黄嘌呤氧化酶(XOD)活性。结果:与模型组比较,土茯苓组小鼠血清UA、TG、胆固醇含量和XOD显著降低(P>0.05或P<0.01)。结论:土茯苓对高尿酸血症模型小鼠肾功能有保护作用,对UA升高有明显的抑制作用。     

Studies on the chemical constituents of Psoralea corylifolia L.

A new isoflavone, corylinin (1), along with six known compounds, isopsoralen (2), psoralen (3), sophoracoumestan A (4), neobavaisoflavone (5), daidzin (6) and uracil (7), have been isolated from the dried fruits of Psoralea corylifolia L. The structure of 1 was established as 7,4′-dihydroxy-3′-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone on the basis of the spectroscopic methods. Structures of the known compounds were identified by comparison of the literature.     

Constituents of the roots ofPueraria lobata inhibit formation of advanced glycation end products (AGEs)

Two isoflavone C-glucosides, puerarin (1) and PG-3 (2), a but-2-enolide, (+/-)-puerol B (3), two isoflavone O-glucosides, daidzin (4) and genistin (5), and three pterocarpans, (-)-medicarpin (6), (-)-glycinol (7) and (-)-tuberosin (8), were isolated from a MeOH extract of the roots of Pueraria lobata, using an in vitro bioassay based on the inhibition of the formation of advanced glycation end products (AGEs) to monitor chromatographic fractionation. The structures of 1-8 were determined by spectroscopic data interpretation, particularly by 1D- and 2D-NMR studies, and by comparison of these data with values in the literature. All of the isolates (1-8) were evaluated for their inhibitory activity on AGEs formation in vitro. Of these, puerarin (1), PG-3 (2), and (+/-)-puerol B (3) exhibited more potent inhibitory activity than the positive control aminoguanidine.     

Mitochondrial apoptosis contributes to the anti-cancer effect of Smilax glabra Roxb

Smilax glabra Roxb. (SGR), a member of the Smilacaceae family and a rhizome of the Liliaceae plant, has shown anti-inflammation and detoxification properties, and a few studies reported its anti-cancer effect. In this study, we showed that SGR inhibited growth of human breast cancer cell line MCF7, colon carcinoma cell line HT-29, and gastric cancer cell line BGC-823 in a dose-dependent manner. Furthermore, SGR could inhibit tumor growth of HT-29 in Balb/c nude mice and murine hepatoma H22 cells in ICR mice. SGR elicited apoptotic cell death, as confirmed by DNA ladder formation, changes in nuclear morphology, and the increased FITC-Annexin-V/PI staining. Permeabilization of mitochondrial membrane (MMP), production of reactive oxygen species (ROS), elevation of intracellular [Ca²⁺], relocation of cytochrome c, and the activation of caspase-3 were found to be associated with the initiation of apoptosis by SGR treatment. Using microarray analysis, we found the changes in expression profiles of genes related to apoptosis, proliferation and cell cycle control in the cells treated with SGR. Our results demonstrated the mitochondrial regulation of apoptosis by which SGR exerts the anti-cancer effect.     

傅里叶变换红外光谱-排序法鉴别土茯苓真伪的研究

目的 建立中成药土茯苓饮片的质量分析方法. 方法 采用水平衰减全反射傅里叶变换红外光谱（HATR-FTIR）法直接测定法获得样品的FTIR,以样品粉末作为比较标准,分别选取31组具有代表性吸收峰的吸光度数据为基础,以样品为分析对象进行主成分分析. 应用主成分析法比较了正伪品之间的差异程度. 结果 FTIR的主成分分析在反映同属不同种及不同属或科植物化学组成差异程度上具有应用价值. 结论 采用FTIR直接测定法并结合主成分分析应用于土茯苓的质量分析,简便、快速、准确,而且不需制备样品.     

Studies on the chemical constituents of Psoralea corylifolia L

A new isoflavone, corylinin (1), along with six known compounds, isopsoralen (2), psoralen (3), sophoracoumestan A (4), neobavaisoflavone (5), daidzin (6) and uracil (7), have been isolated from the dried fruits of Psoralea corylifolia L. The structure of 1 was established as 7,4'-dihydroxy-3'-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone on the basis of the spectroscopic methods. Structures of the known compounds were identified by comparison of the literature.