Impact of Wortmannilactone F and G31P on Clonorchis Sinensis-infected mice

Clonorchis sinensis could induce inflammation, epithelial hyperplasia and fibrosis in the intrahepatic bile duct as a food-borne parasite, which was associated with the development of cholangiocarcinoma (CCA). Praziquantel was the most effective drug on treatment of this kind of parasite. However, new drugs with minimal toxicity to the host were urgently needed due to the side effects of Praziquantel and its CCA risk. In this study, helminth mitochondria respiratory chain blocker Wortmannilatone F (WF) and IL-8 analogue CXCL8 (3–72) K11R/G31P were used to treat BALB/C mice infected by Clonorchis sinensis. We investigated the gross and histopathological morphology of the liver, inflammation-associated cytokine IL-6, lipid peroxidation-related proteins cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), collagen fiber accumulation and fibroblast-specific protein 1 (FSP1), malignant markers proliferating cell nuclear antigen (PCNA) and cytokeratin 19 (CK19), as well as the disinfection effect on these parasites in vitro. WF inhibited and killed the worms dramatically, and the combination of WF with G31P improved the condition of the hepatobiliary duct tissue greatly. These outcomes indicated that the combination of WF and G31P was a potential therapeutic method to treat the Clonorchis sinensis infection.     

大叶秦艽花与麻花秦艽花抗炎镇痛作用的研究

目的研究大叶秦艽花与麻花秦艽花的抗炎镇痛作用。方法采用二甲苯所致小鼠耳肿胀和大鼠角叉菜胶足趾肿胀模型,研究大叶秦艽花与麻花秦艽花的抗炎作用;采用热板法、醋酸扭体法、光照甩尾法,研究大叶秦艽与麻花秦艽的镇痛作用。结果大叶秦艽、麻花秦艽能减轻二甲苯所致小鼠耳肿胀的体积和大鼠角叉菜胶足趾肿胀率;提高热板法引起小鼠的痛阈值及延长光电甩尾法所致的潜伏期;显著地减少醋酸引起的扭体次数。结论大叶秦艽花与麻花秦艽花具有较好的抗炎、镇痛作用。     

In vitro inhibition of prostaglandin synthesis by antithyroid drugs.

Methimazole inhibited the release of PGE₂ and PGF_2α by dog thyroid slices: at 1 mM, the inhibition was 70% for PGE₂ and 63% for PGF_2α. The concentrations required to inhibit prostaglandin synthesis (0.1–1 mM) were much higher than those which depressed protein iodination (1–10 μM). A similar inhibition of prostaglandin synthesis was obtained with carbimazole, propylthiouracil and aminotriazole, but not with imidazole. Basal release and release stimulated by ionophore A₂₃₁₈₇, carbamylcholine and epinephrine were decreased to the same extent. Methimazole also inhibited the release of PGE₂ and PGF_2α by slices of dog renal cortex and inner medulla. The conversion of arachidonic acid to PGF_2α and PGE₂ by a dog kidney medulla homogenate was depressed by methimazole. The antithyroid drugs constitute a new class of prostaglandin synthesis inhibitors.     

Enhancement of mutagenic activity in Salmonella by contraceptive steroids

Two oral contraceptive steroids, mestranol and norethynodrel, were evaluated for mutagenicity in the Salmonella histidine reversion assay. The pure forms of the hormones were not mutagenic when tested with either missense (TA1535, TA100) or frameshift (TA98, TA1538, TA1537) strains. In vitro activation of the hormones with liver homogenates from rats induced either with phenobarbital or Aroclor did not influence these results. However, mestranol was capable of enhancing the mutation yield obtained by an ineffective subthreshold dose of 2-acetylaminofluorene. Dimethyl sulfoxide extracts of two contraceptive pills, Ovulen-21 (containing mestranol) or Enovid-E (containing mestranol or norethynodrel), also were nonmutagenic. But again, both these extracts were capable of enhancing the mutation yield induced with an ineffective dosage of 2-acetylaminofluorene and N-nitrosopiperidine. These studies point to the possible promotional effect and subsequent potential hazard to the female consumers who use these hormones as a means of pregnancy control.     

滨海前胡与白花前胡的化学成分比较

用气相色谱－质谱－计算机联用系统对滨海前胡果实挥发油成分进行研究,以ＳＥ－５４石英毛细管柱共分离出４２个峰,鉴定出２４个化学成分,占挥发油总量的９４．６８％,并用薄层层析,紫外光谱,脉冲极谱等方法对滨海前胡根、茎叶的化学成化进行研究,结果显示它们的主要成分和正品白花前胡根本一致。     

HPLC法测定人参、西洋参和三七不同部位中人参皂苷的含量

目的:为了探讨人参、西洋参和三七中人参皂苷的资源含量,以确保人参、西洋参和三七中人参皂苷资源充分被利用,为开发以人参皂苷为主的创新药物提供科学数据。方法:采用高效液相色谱法对人参、西洋参和三七不同部位中人参皂苷的含量进行测定。色谱条件为:Agilent 1100 Series 高效液相色谱仪;色谱柱为德国 Nucleosil-C_(18)(4.6 mm×150 mm,5μm);流动相为水-乙腈梯度洗脱,流速1.5 mL·min~(-1);A为水,B为乙腈;梯度洗脱程序为:0～16 min,56%B;16～20 min,56%→100%B;20～38 min,100%B;38～45 min,100%→56%B;45～60 min,56%B;60～70 min,56%B。所有组分均70 min 内出完。检测波长203 nm,柱温35℃,灵敏度为0.02AUFS。线性关系考察r=0.9994;精密度试验 RSD=0.26%,平均回收率为99.88%,重现性试验 RSD=2.0%,分离度为R=3.042。结果:人参须根含有较高的人参皂苷 Rb_1(1.082%),人参茎叶则含有较高的人参皂苷 Rc(1.002%)、Re(3.430%)和 Rg_1(1.303%);西洋参根含有较高的人参皂苷 Rb_1(2.213%)和 Re(0.9188%),西洋参芦头中含有较高的人参皂苷 Rb_1(2.840%)和Re(1.224%);三七根含有较高的人参皂苷 Rb_1(2.163%)和 Rg_1(2.633%),三七芦头中含有较高的人参皂苷 Rb_1(4.376%)和 Rg_1(4.145%)。结论:高效液相色谱法分离、分析人参皂苷效果好、准确、迅速、简便,也可作为评价人参属植物质量的有效分析方法。建议对人参、西洋参和三七中含量较高的人参皂苷进行提取分离,直接用于创新药物的开发。     

广西莪术的叶、根茎和块根中挥发油GC-MS对比分析

目的：对广西莪术叶中挥发油成分进行系统的分析,并与其传统的用药部位块根和根茎的挥发油成分对比,寻找广西莪术叶作为代替性药材的可能性,尽可能的扩大广西莪术的药用部位,提高广西莪术整株植物的经济效益。方法：采用水蒸气蒸馏法提取挥发油,运用GC/MS方法比较叶与根茎,块根的化学成分及其各成分的相对百分含量。结果：从广西莪术叶中分离得到38个色谱峰,鉴定出26种成分。结论：首次从广西莪术叶中鉴定出26种挥发性成分,叶中所含成分与根茎、块根的差别较大,但也含有部分抗肿瘤成分。     

Synthesis,characterization and cytotoxic activity of naturally isolated naringin-metal complexes

High-purity naringin was isolated from the fruit peels of Citrus maxima and characterized by various spectroscopic methods like UV and NMR. The isolated compound ligand (HL) was used as ligand-metal complexes synthesis after using Ag (I), Y (III) and Ru (III) metals. These ligand-metal complexes were characterized by elemental analysis, FT-IR, UV–VIS, TGA, molar conductance and magnetic properties. Cytotoxic activity of the isolated naringin and its metal complexes were investigated against two human cancer cell lines namely, white breast Adenocarcinoma (MCF7) and Lung carcinoma (A549) using cell viability assay. Transition metal increased the cytotoxic activity of naringin when they were conjugated. LC50 of Ag ligand complex demonstrated strong cytotoxicity against MCF-7 and A549 cell line that was found higher active more than three and four times the strength, respectively when compared to LC50 of Adriamycin. While LC50 of Adriamycin compound was slightly more active only about 30% and twice the strength of the Ru ligand complex against MCF-7 and A549 cell line, respectively.     

丽珠肠乐、思密达联合治疗小儿腹泻临床观察

目的观察比较丽珠肠乐、思密达联合治疗小儿腹泻的疗效。方法随机选择小儿腹泻92例,分成3组,A组33例,采用丽珠肠乐和思密达联合治疗;B组28例,仅采用丽珠肠乐治疗;C组31例,单采用思密达治疗。结果 92例经丽珠肠乐、思密达或丽珠肠乐或思密达治疗后,A组显效24例,有效8例,无效1例,总有效率97.0%,明显高于单用任何一种。结论腹泻疾病在基础治疗上加用丽珠肠乐、思密达联合治疗可以获得显著疗效。     

Mechanism-based inhibition of human Cytochrome P450-3A activity by grapefruit hybrids having low furanocoumarin content

1. A citrus breeding program aimed at developing low furanocoumarin (FC) grapefruit cultivars provided 40 grapefruit juice (GFJ) samples containing variable concentrations of FC derivatives, established as being mechanism-based (irreversible) inhibitors of human CYP3A isoforms.

2. The principal inhibitory FCs were identified as 6′,7′-dihydroxybergamottin, along with a series of dimeric compounds (spiroesters) having high inhibitory potency.

3. A random subset of the GFJ samples (n = 25) were tested as CYP3A inhibitors using an in vitro model based on human liver microsomal metabolism of the index substrate triazolam. The reciprocal values of in vitro 50% inhibitory concentrations (IC₅₀) were highly correlated with concentrations of inhibitory FCs in the GFJ samples (r² = 0.96). However the correlations were driven mainly by a few samples having high FC content and high reciprocal IC₅₀ (corresponding to low IC₅₀). Among the rest of the samples, the relationship was less robust.

4. Further study is needed to determine how low the FC content needs to be (or how high the IC₅₀ needs to be) to assure minimal risk of clinical interactions involving GFJ and CYP3A substrate drugs.

     

The reductive metabolism of halogenated alkanes by liver microsomal cytochrome P450

Under anaerobic conditions various polyhalogenated alkanes (CCl₃-CCl₃, HCl₂C-CCl₃, CF₃-CCl₃, CCl₄, CF₃-CHClBr) stimulate the oxidation of NADPH by liver microsomal fractions. The participation of cytochrome P450 in the NADPH oxidation was shown by inducers and inhibitors of the monooxygenase system. The products of the reductive pathway of hexachloroethane were tetrachloroethene (99.5%) and pentachloroethane (0.5%). From pentachloroethane as substrate trichloroethene (96%) and tetrachloroethane (4%) were produced. The stoichiometry of NADPH oxidation and product formation was close to 1:1. There was a synergistic effect in the presence of NADPH and NADH for both hexa- and pentachloroethane. The influence of dioxygen and radical traps (RSH) on the formation of products from hexachloroethane with reduced cytochrome P450 has been investigated. The results indicate the possibility of a reductive in vivo metabolism of polyhalogenated alkanes even at physiological dioxygen concentrations. For the reductive dehalogenation of polyhalogenated alkanes by microsomal cytochrome P450 a reaction scheme is proposed: the reduction proceeds by two subsequent one electron reductions forming first a radical and then a carbanion. The carbanion can form an alkene via β-elimination of chloride.     

HPLC-FLD测定多种植物提取物中苯并(a)芘的含量

目的建立测定植物提取物中苯并(a)芘含量的方法。方法采用HPLC-FLD法,用Agilent Li Chrospher PAH色谱柱(250 mm×4.6 mm),流动相为乙腈,检测器为荧光检测器(λex=365 nm,λem=470 nm),流速为1.0 ml.min-1,柱温30℃,进样量10μl。结果线性范围为1~25 ng.ml-1(r=0.9995);平均回收率为97.67%(RSD=9.85%)。结论所建方法重复性好、精密度高、能准确快速地测定植物提取物中苯并(a)芘的含量。     

高效液相色谱法测定显脉獐牙菜中獐牙菜苦苷的含量

目的建立测定显脉獐牙菜中獐牙菜苦苷含量的高效液相色谱方法。方法C18（4.6 mm×200 mm,5μm）色谱柱,流动相为甲醇-水（25∶75）,流速为1.0 mL·min^-1,检测波长为239 nm,柱温为25℃。结果獐牙菜苦苷在1.52-15.22μg线性良好,相关系数r为0.999 95,平均回收率为97.8%,RSD小于3%（n=6）。结论本方法操作简便,分离效果好,灵敏度高,重现性好,可为显脉獐牙菜质量控制提供参考。     

Enhancement of transformed foci and induction of prostaglandins in Balb/c 3T3 cells by palytoxin: in vitro model reproduces carcinogenic responses in animal models regarding the inhibitory effect of indomethacin and reversal of indomethacin's effect by exogenous prostaglandins.

Cell transforming activity of palytoxin, a non-TPA type tumor-promoter, was investigated with the two-stage transformation assay using Balb/c 3T3 cells. Palytoxin showed potent promoting activity; treatment at 1.9 pM or more increased the number of transformed foci after initiation by 3-methylcholanthrene (MCA). Determination of prostaglandin (PG) E2 and PGF(2alpha) concentrations in the culture medium revealed that palytoxin (1.9-3.7 pM for 24 h) stimulated the production of PG in Balb/c 3T3 cells (the concentration reached 3-4 microM), and treatment with PGE2 or PGF(2alpha) itself increased the number of transformed foci of Balb/c 3T3 cells after initiation by MCA. Neither palytoxin nor PGs showed initiating activity. Indomethacin suppressed the promoting activity of palytoxin, but not that of PGE2 and PGF(2alpha). Interestingly, concomitant treatment with PGE2 or PGF(2alpha) in addition to indomethacin markedly reversed the suppressive effect of indomethacin. These findings indicated that the in vitro transformation model could reproduce experiments that have been performed in animal models regarding the inhibitory effect of indomethacin on carcinogenic responses and reversal of indomethacin's effect by exogenous prostaglandin and, therefore, may provide insight into molecular modes of action of palytoxin. In the present study, palytoxin also induced prostaglandin synthesis, and therefore, the Balb/c 3T3 cell model should provide insight into the molecular mechanism by which palytoxin regulates prostaglandin biosynthesis.