New labdane diterpenoids from Leonurus japonicus and their anti-inflammatory activity

Two new, 16-oxo-leoheteronone A (1) and 15-methoxyleoheteronin B (2), and four known, 8,9-secohispanolone (3), galeopsin (4), hispanone (5), and leoheteronin B (6), labdane diterpenoids were isolated from the aerial parts of Leonurus japonicus. Compound 3 was isolated for the first time as a naturally occurring compound. Structures of the two compounds were determined on the basis of extensive spectroscopic techniques, including 1D, 2D NMR, and HREIMS. In addition, compounds 1–3, 5 and 6 were examined for inhibition of superoxide anion generation and elastase release, and the results suggested that compound 5 possesses anti-inflammatory activity.     

Semisynthesis of epoxy-pimarane diterpenoids from kirenol and their FXa inhibition activities

Kirenol is one of the biologically active diterpenoids from Siegesbeckia pubescens. In terms of the high content and typical structure, many ent-diterpenoids separated from S. pubescens were presumed to be biologically related to kirenol. Among them, epoxy-pimarane diterpenoids are belonging to a special family of naturally occurring compounds that attracted our attentions on their putative biosynthesis pathway and biological activities. Here, we designed and synthesized two known 14,16-epoxy-pimarane diterpenoids (2 and 3) and five 8,15-epoxy-pimarane diterpenoids (4–8) from kirenol. Their absolute structures were determined by 1D and 2D NMR data and the absolute configurations of 4 were confirmed by X-ray crystallographic data. Their inhibition effects on factor Xa (FXa) were evaluated to assess the potentiality of epoxy-pimarane diterpenoids as FXa inhibitor agents.     

Isopimarane diterpenoids from Aeollanthus rydingianus and their antimicrobial activity

Four acyloxy-isopimarane derivatives along with two known isopimarane diterpenoids, the flavone cirsimaritin and the sterols β-sitosterol and stigmasterol were isolated from the aerial parts of Aeollanthus rydingianus. The structures of the compounds were established on the basis of spectroscopic analysis and chemical evidence. The isolated substances were screened for antimicrobial activity against Gram-positive and Gram-negative bacteria and a yeast strain. 19-Acetoxy-7,15-isopimaradien-3β-ol and 7,15-isopimaradien-19-ol showed minimum inhibitory concentration (MIC) values of 3.90–15.62 μg/ml for Staphylococcus aureus and of 7.81 μg/ml for Enterococcus hirae.     

Abietane diterpenoids from the root of Salvia lavandulaefolia

Two new derivatives of royleanone, 7α-ethoxyroyleanone and 7α-ethoxy-12-O-methyl-royleanone, besides the previously known diterpenes royleanone, 6,7-dehydroroyleanone, 7α-acetoxyroyleanone and inuroyleanol, have been isolated from the root of Salvia lavandulaefolia. The triterpenoid O-acetyloleanolic aldehyde has also been obtained from the same source.     

Isolation and characterization of two new diterpenoids from Stachys parviflora: Antidiarrheal potential in mice

Two new diterpenoids trivially named Stachysrosane (1) and Stachysrosane (2) have been isolated from the ethyl acetate soluble fraction of Stachys parviflora. The structure elucidation of isolated diterpenoids were based on one-(1D) and two-dimensional (2D)-NMR techniques including correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond correlation (HMBC), and nuclear Overhauser effect spectroscopy (NOESY). The isolated diterpenoids 1 and 2 caused marked attenuation of castor oil induced diarrhea in dose dependent manner with 100% and 70% protection at 45 mg/kg p.o. respectively. It can be concluded with confidence that both the isolated compounds could be useful antidiarrheal agents; however, detailed studies will be needed.     

基于网络药理学及分子对接的浙贝母花-枇杷花药对止咳化痰作用机制研究

采用网络药理学及分子对接阐明浙贝母花—枇杷花药对的止咳化痰作用机制.以口服生物利用度≥30％和类药性≥0.18筛选成分,Swiss Target Prediction数据库进行靶点预测,GenCLiP 3和Drugbank数据库进行疾病靶点分析.以STRING和Cytoscape软件构建成分—靶点互作图,并进行GO、K...     

Neo-clerodane diterpenoids from Teucrium chamaedrys: The identity of teucrin B with dihydroteugin

The previously proposed structure for teucrin B [15,16-epoxy -1,7-dihydroxy-cleroda-13(16),14-diene- 18,19:20,12-diolide] must be amended to 15,16-epoxy-2β,6β-dihydroxy-neo-cleroda-13(16), 14-diene-18,19:20,12S-diolide, which corresponds to the structure that has been established for dihydroteugin.     

Isolation and structural elucidation of two new labdane diterpenoids from the aerial part of Roylea cinerea

Two new labdane diterpenoids, cinereanoid A (1) and cinereanoid B (2), along with five known compounds, calyone (3), pilloin (4), 1-methylindole-3-carboxaldehyde (5), β-sitosterol (6) and stigmasterol (7) were isolated from the aerial parts of Roylea cinerea (Lamiaceae). The new structures were determined by using IR, MS, 1D, 2D NMR spectroscopy. The structure of both new compounds was further confirmed by single crystal X-ray crystallographic analysis. In this study we have also reported single crystal X-ray structure of compound 3 which unambiguously confirmed the relative stereochemistry of tertiary hydroxyl and methyl groups, as it was not established by earlier report. Compounds 4 and 5 were isolated for the first time from this plant. In view of very few reports about this species, this report has increased the phytochemical knowledge about R. cinerea.     

Exenatide-loaded PLGA microspheres with improved glycemic control: In vitro bioactivity and in vivo pharmacokinetic profiles after subcutaneous administration to SD rats

A subcutaneous exenatide delivery system was developed and characterized in vitro and in vivo. The results clearly showed that the exenatide loaded PLGA microspheres prepared by using a non-aqueous processing medium had low burst release and high drug encapsulation efficiency. Exenatide loaded in the microspheres preserved its bioactivity. The pharmacokinetics parameters were determined after subcutaneous administration of microspheres to SD rats. The plasma concentration of the single dose of the sustained-release microspheres attained C_max of 108.19 ± 14.92 ng/ml at t_max of 1.33 ± 0.58 h and the t_1/2 was 120.65 ± 44.18 h. There was a linear correlation between the in vitro and in vivo release behavior (R² = 0.888). Exenatide loaded microspheres may prove to have great potential for clinical use.     

金银花五个品系的RAPD分析及DNA指纹图谱的建立

运用RAPD技术,对5个金银花品系进行遗传多样性研究并构建这5个金银花品系的DNA指纹图谱。从80个引物中筛选出25个带纹清晰,多态性好的引物用于实验。其中,引物SBSD06的扩增条带可以清楚明确区分5个品系,建立其DNA指纹图谱。在清晰、稳定出现的170条带中,153条带具有多态性。按UPGMA法进行聚类分析,计算其遗传相似系数,结果显示,金银花5个品系聚为两类,与其形态学分类结果相符。     

Chromatographic determination of 7,8-methylenedioxy-4H-2,3-benzodiazepin-4-ones in rat plasma: relationship to their anticonvulsant activity

The present investigation was designed to develop an assay suitable for pharmacokinetic studies of new compounds, i.e. the novel 7,8-methylenedioxy-4H-2,3-benzodiazepin-4-one derivatives (2a and 2b), acting as non-competitive AMPA-receptor antagonists. A reversed-phase high-performance liquid chromatographic method has been developed to determine the time-course of plasma concentrations of derivatives 2a and 2b administered intraperitoneally to Sprague-Dawley rats. The separation of compounds studied and a N-methyl-2,3-benzodiazepin-4-one derivative as internal standard (I.S.) from plasma, were carried out by liquid-liquid extraction using diethyl ether. The samples were injected onto the analytical column (Partisil 10 ODS) eluted with acetonitrile/0.01 M acetate buffer (pH 5.3) at a flow-rate of 2 ml/min and detected at 240 nm. Compounds 2a, 2b and I.S. gave retention times of 8.5, 5.25 and 11.1 min, respectively. The selectivity of the method was satisfactory. The mean recovery from spiked rat plasma ranged from 86.7 to 91.6% for 2a, and from 85.1 to 87.0% for 2b. The procedures were validated with a good reproducibility and linear response from 0.0625 to 2 microg/ml, with a regression coefficient of 0.9932 for 2a and 0.9854 for 2b. The lower limit of quantification (LOQ) was taken as 15 ng/ml for the two compounds. 2a and 2b showed no signs of significant degradation in rat plasma during storage at -20 degrees C and following freeze/thaw cycles. Moreover, plasma levels of the tested compounds have been correlated with their anticonvulsant activity, determined in vivo in genetically epilepsy-prone rats. Due to its sensitivity, the method was suitable for application to pharmacokinetic study.     

Anti-inflammatory activities of isopimara-8(14),-15-diene diterpenoids and mode of action of kaempulchraols P and Q from Kaempferia pulchra rhizomes

Inflammation is an extensively recognized link to many pathological diseases. It is a host response for protection from infections and tissue damage. Infections trigger acute inflammation; however, persistent infection will contribute to chronic inflammation and higher disease susceptibility. Deregulated inflammatory responses can cause excessive or long-lasting tissue damage, manifested as cancer, immune disorders, diabetes, etc. NF-κB is a central mediator of pro-inflammatory gene induction and functions in both innate and adaptive immune cells; therefore, the anti-inflammatory regulation of NF-κB is needed. Natural products reportedly play an important role in controlling the inflammatory response pathways. However, the anti-inflammatory activities of isopimara-8-(14),15-diene diterpenoids have not yet been fully elucidated. To elucidate the anti-inflammatory activities of the isopimara-8(14),15-diene diterpenoids, we investigated 21 isopimara-8(14),15-diene diterpenoids previously isolated from Kaempferia pulchra rhizomes. Eleven compounds exhibited NO inhibitory activity against lipopolysaccharide (LPS)-induced RAW264.7 cells, with IC₅₀ values ranging from 30 to 100 μM. Furthermore, the most potent kaempulchraols P and Q, with IC₅₀ values of 39.88 and 36.05 μM, respectively, inhibited the NF-κB-mediated transactivation of a luciferase reporter gene, IL-6 production, and COX-2 expression, with an effective dose of 25 μM. These findings provide new insights into the anti-inflammatory activities of the isopimara-8(14),15-diene diterpenoids.     

泡桐花体外抑菌作用及黄酮含量的测定

本文首次采用滤纸片法对泡桐花提取液的不同萃取部分进行了体外抑菌试验并用紫外分光光度法对泡桐花的花冠和花萼中总黄酮含量进行了测定。结果表明不同萃取部分对金黄色葡萄球菌,大肠杆菌,枯草芽孢杆菌均有不同程度的抑制作用,其中对金黄色葡萄球菌作用最强,而对黑曲霉,啤酒酵母,产黄青霉无明显抑制作用。含量测定表明花萼中黄酮含量明显高于花冠。     

Determination and pharmacokinetic study of chiisanogenin in rat plasma by ultra performance liquid chromatography-tandem mass spectrometry

Introduction – Chiisanogenin existing in many Acanthopanax species has been reported to possess anti‐inflammatory, antibacterial and antiplatelet aggregatory activities. Objective – To develop and validate a rapid and sensitive ultra performance liquid chromatography‐tandem mass spectrometry method for the determination of chiisanogenin in rat plasma and to investigate its pharmacokinetics after oral administration of chiisanogenin or the extract of Acanthopanax sessiliflorus fruits. Methodology – The sample pretreatment involved a one‐step extraction of 0.2 mL plasma with diethyl ether. Acetaminophen was used as the internal standard. The separation was carried out on an ACQUITY UPLC? BEH C₁₈ column with a mobile phase of acetonitrile‐5 mM ammonium acetate (90:10, v/v) at a flow rate of 0.2 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. Results – A high sample throughput was achieved with an analysis time of 1.1 min per sample. The calibration curve was linear (r² ≥ 0.99) over the concentration range of 5–500 ng/mL with a lower limit of quantification (LLOQ) of 5 ng/mL. The intra‐day and inter‐day precision (relative standard deviation, R.S.D.) values were below 11% and the accuracy (relative error, R.E.) was within 8% at all three quality control (QC) levels. Conclusion – The method was successfully applied to the pharmacokinetic study of chiisanogenin in rat after oral administration of chiisanogenin and the extract of Acanthopanax sessiliflorus fruits. Other constituents in the extract affected the pharmacokinetic behavior of chiisanogenin. Copyright © 2010 John Wiley & Sons, Ltd.     

Phenolic diterpenoids of podocarpus ferrugineus and other podocarps

19-Hydroxyferruginol and 19-acetoxyferruginol, two new naturally occurring phenolic diterpenoids, have been isolated from the heartwood of Podocarpus ferrugineus. Totarol and its derivatives have been obtained from Podocarpus affinis, P. falcatus, P. koordersii, Dacrycarpus vieillardii and Decussocarpus comptonii and podocarpic acid from Falcatifolium taxoides.     

Determination and variation of three active diterpenoids in Andrographis paniculata (Burm.f.) Nees

Simple and rapid methods have been developed for the extraction and simultaneous determination of the three active diterpenoids, andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3) and neoandrographolide (AP4), from various samples of Andrographis paniculata (Burm.f.) Nees. Methanol extracts from the dried leaves, stems and crude products were analysed by isocratic HPLC using a methanol and water mobile phase with monitoring at 220 nm. There was a large variation of the three active diterpenoids in different A. paniculata products obtained from Thai markets. The results indicated that the amounts of these active compounds consumed, based on the recommended daily doses, from materials obtained from the different suppliers will be different. In addition, the stability of these three active compounds was also examined in dry herbs stored at room temperature. The results showed that andrographolide was more stable than the others. In contrast, the content of 14-deoxy-11,12-didehydroandrographolide increased and the neoandrographolide content fluctuated during storage time. The combination of different levels of these compounds in the source materials and the changes during storage could have a significant effect on the efficacy of this traditional herbal medicine in clinical treatment.     

金银花活性成分、药理作用及其应用

本文综述了中药金银花的活性成分、药理作用的研究进展及开发利用概况.说明金银花在医药、食品、轻化产品等方面具有广泛的用途.     

不同品种药用菊花中游离糖类及游离氨基酸含量的HPLC分析

为比较不同品种菊花的品质特征,本文采用HPLC法测定其游离糖类及游离氨基酸的含量.结果表明,不同品种菊花中游离糖类主要成分是果糖和葡萄糖,蔗糖和麦芽糖未检出,总游离糖类含量约为9.07～18.76g/1O0g,其中黄山贡菊中含量最高,为18.76g/100g,黄菊中最低,为9.07g/100g;其总游离氨基酸含量约为0.563～2.806g/100g,七月菊中含量最高,为2.806g/100g,杭白菊中最低,为0.563g/100g.     

Potential pharmacodynamic and pharmacokinetic interactions of Nigella Sativa and Trigonella Foenum-graecum with losartan in L-NAME induced hypertensive rats

The objective of this investigation was to study whether Nigella Sativa and Trigonella Foenum-graecum, could modulate the losartan pharmacodynamic (PD) and pharmacokinetic (PK) in experimental L-NAME induced hypertensive rats. For in vivo study, the systolic blood pressure (SBP) of rats was measured by the “tail-cuff system” after the treatment of rats with herb alone and herb + losartan in hypertensive rats. The SBP of rats treated with L-NAME + losartan also recorded. For the PK study, blood samples were obtained for up to 12 h to determine the concentrations of the drug, and various PK parameters were calculated. The data displayed that the SBP was significantly (p < 0.05) decreased in the rats when administered with L-NAME + N. Sativa or L-NAME + T. Foenum-graecum in contrast to the rats administered with L-NAME alone. A more prominent decline (p < 0.05) in SBP was detected in rats administered with L-NAME + N. Sativa + losartan and L-NAME + T. Foenum-graecum + losartan. In a PK study, higher losartan C_max and AUC_0-t were noted in rats treated with N. Sativa + losartan and T. Foenum-graecum + losartan, although the difference was not significant in contrast to the control group. This study proposed that the interaction between N. Sativa & losartan and T. Foenum-graecum & losartan could take place on concurrent administration; consequently, the dose of losartan may need to be accustomed when they are utilized simultaneously.