A new sesquiterpene lactone glycoside and a new quinic acid methyl ester from Patrinia villosa

A new sesquiterpene lactone glycoside (1) and a new quinic acid methyl ester (2) were isolated from Patrinia villosa, together with another two known compounds chlorogenic acid n-butyl ester (3), 3, 4-di-O-caffeoylquinic acid methyl ester (4). Their structures were established using 1D/2D-NMR spectroscopy, mass spectrometry, and comparing with spectroscopic data reported in the literature.     

Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver,kidney and pancreas tissues of STZ-induced diabetic rats: A mechanistic study

The aim of this study was to investigate the synergistic effects of quercetin (QE) and quinic acid (QA) on a STZ-induced diabetic rat model to determine their potential role in alleviating diabetes and its associated complications. In our study design, diabetic rats were treated with single and combined doses of QE and QA for 45 days to analyse their effects on liver, kidney and pancreas tissues. The study result showed that QE and QA treated groups down-regulated hyperglycaemia and oxidative stress by up-regulating insulin and C-peptide levels. Moreover, histological observations of the liver, kidney and pancreas of diabetic rats treated with single and combined doses of QE and QA showed a significant improvement in the structural degeneration. Interestingly, the combination dose of QE and QA (50 mg/kg) exhibited maximum inhibition of the pro-apoptotic protein Bax expression and demonstrate enhancement of the anti-apoptotic protein Bcl-2 expression in the kidney tissues, suggesting a protective role in the kidneys of diabetic rats. Taken together, these results indicates the synergistic effects of QE and QA in ameliorating hyperglycaemia, hyperlipidemia and insulin resistance in diabetic rats and therefore, open a new window of research on the combinatorial therapy of flavonoids.     

A new ferulic acid ester and other constituents from Dracocephalum peregrinum

A new ferulic acid ester, 1′-methyl-2′-hydroxyethyl ferulate (1), together with methylcaffeate (2), 4-hydroxy cinnamic acid (3), ferulic acid (4), caffeic acid (5), diosmetin (6), luteolin (7), 5,3′,4′-trihydroxy-3,7-dimethoxyflavone (8), eriodictyol (9), kaempferol (10), quercetin (11), acacetin-7-O-glcopyranoside (12), 4-(β-glucopyranosyloxy) benzoic acid (13), luteolin-7-O-(6″-feruloyl) glucopyranoside (14), luteolin-7-O-glucopyranoside (15), kaempferide-3-O-rhamnopyranoside (16), quercitrin (17), kaempferol-3-O-glucopyranoside (18), prunasin (19), quercetin-7-O-glucopyranoside (20), quercetin-3-O-glucopyranoside (21), plantaginin (22), linarin (23), luteolin-7-O-rutinoside (24), and chlorogenic acid (25) were isolated from the aerial parts of Dacocephalum peregrinum. The structure of 1 was elucidated on the basis of spectroscopic and HR-ESI-MS analyses. In addition, compound 1 exhibited mild inhibitory effect on NO production in LPS-stimulated RAW264.7 cells.     

Alkaloid profiling in crude and processed Strychnos nux-vomica seeds by matrix-assisted laser desorption/ionization-time of flight mass spectrometry

Direct analysis of alkaloids in the tissues of crude and processed Strychnos nux-vomica seeds by MALDI-TOFMS was described. The alkaloid profiles of the herb drugs were obtained without the need of complicated sample preparation to avoid potential damage or change of the active components. Seed tissues that were optimally sliced to a thickness of 10-20 microm from the crude and processed Strychnos nux-vomica seeds as well as various parts of tissue such as endosperm and epidermis were analyzed on MALDI target plate after the matrix was directly applied onto the tissue surface. The obtained alkaloid profiles provided valuable information for the differentiation of crude and processed Strychnos nux-vomica seeds and for the explanation of the significantly different toxicity. Experimental results indicated that the direct MALDI-TOFMS analysis allowed rapid screening of the alkaloid components in Strychnos nux-vomica seeds.     

Application of a new optimization strategy for the separation of tertiary alkaloids extracted from Strychnos usambarensis leaves

The HPLC separation of six alkaloids extracted from Strychnos usambarensis leaves has been developed and optimized by means of a powerful methodology for modelling chromatographic responses, based on three steps, i.e. design of experiments (DoE), independent component analysis (ICA) and design space (DS). This study was the first application of a new optimization strategy to a complex natural matrix. The compounds separated are the isomers isostrychnopentamine and strychnopentamine, 10-hydroxyusambarine and 11-hydroxyusambarine, also strychnophylline and strychnofoline. Three LC parameters have been optimized using a multifactorial design comprising 29 experiments that includes 2 center point replicates. The parameters were the percentage of organic modifiers used at the beginning of a gradient profile which consisted in different proportions of methanol (MeOH) and acetonitrile (MeCN), the gradient time to reach 70% of organic modifiers starting from the initial percentage and the percentage of MeCN found in the mobile phase. Subsequent to the experimental design application, predictive multilinear models were developed and used in order to provide optimal analytical conditions. The optimum assay conditions were: methanol/acetonitrile-sodium pentane sulfonate (pH 2.2; 7.5 mM) (33.4:66.6, v/v) at a mobile phase flow rate of 1 ml/min during a 40.6 min gradient time. The initial organic phase contained 3.7% MeCN and 96.3% MeOH. The method showed good agreement between the experimental data and predictive value throughout the studied parameters space. Improvement of the analysis time and optimized separation for the compounds of interest was possible due to the original and powerful tools applied. Finally, this study permitted the acquisition of isomers profiles allowing the identification of the optimal collecting period of S. usambarensis.     

UPLC-MS/MS法测定茯苓、茯苓皮和茯神中茯苓新酸B、去氢土莫酸、猪苓酸C、去氢茯苓酸和茯苓酸

目的 建立超高效液相色谱串联质谱（UPLC-MS/MS）法同时测定茯苓、茯苓皮和茯神中茯苓新酸B、去氢土莫酸、猪苓酸C、去氢茯苓酸和茯苓酸。方法 采用Shim-pack GIST C₁₈ AQ色谱柱（100 mm×2.1 mm,3 μm）,以乙腈–0.1%甲酸为流动相,梯度洗脱,体积流量0.4 mL/min,柱温40 ℃,进样量5 μL。质谱采用离子源：ESI,负离子模式采集,采集模式：多反应监测（MRM）,离子源温度150 ℃,毛细管电压2.5 kV,锥孔电压40 V,去溶剂气流量900 L/h,去溶剂气温度500 ℃。结果 茯苓新酸B、去氢土莫酸、猪苓酸C、去氢茯苓酸和茯苓酸在各自的线性范围内线性关系良好,平均回收率分别为97.80%、99.65%、97.32%、102.82%、99.57%,RSD值分别为3.46%、1.29%、3.01%、3.11%、1.89%。茯苓皮中5种三萜类成分含量均高于茯苓和茯神。结论 本法具有分析速度快、准确度高的优点,可为茯苓、茯苓皮和茯神的质量标准提高和开发利用提供依据。     

Isolation of a new quinic acid derivative and its antibacterial modulating activity

Background and the purpose of the study

The species Hymenocrater calycinus, belongs to the plant family Lamiaceae and grows wildly in the north-east of Iran. Previously, the antimicrobial activity of the plant extracts was reported. In the present study, the bioactivity-guided fractionation of the methanol extract of H. calycinus and the combination effects of the isolated compound with cell wall active agents against S. aureus and E. coli was investigated.

Methods

Column and thin layer chromatographic methods were used for isolation and purification and spectroscopic data (MS, ¹H- and ¹³C-NMR, HMQC, HMBC and ¹H-¹H COSY) were employed for identification of the compound isolated from the extract. A disk diffusion method was used to determine the antibacterial activity of the isolated compound against S. aureus and E. coli in comparison with 7 different antibiotics.

Results

The isolated compound 1 was identified as 3-(3, 4- dihydroxyphenyl) lactic acid 2-O-quinic acid. Compound 1 (500 µg/disc) enhanced antibacterial effect of ampicillin, ciprofloxacin, vancomycin and cefepime against S. aureus and activated the effects of ampicillin and vancomycin against E. coli.

Conclusion

Results showed that the compound 1 was not active against both tested strains at any concentration below 1 mg/disk, and as a result the enhancing effect of the compound could be due its association with antibiotics.     

新型非环核苷膦酸L-氨基酸酯类化合物的设计、合成与抗乙型肝炎病毒活性

设计合成具有抗乙型肝炎病毒活性的非环核苷膦酸双L-氨基酸酯系列衍生物。以adefovir dipivoxil为先导化合物， 根据核苷L-氨基酸酯前药提高生物利用度及抗病毒活性的研究结果对先导化合物进行结构优化， 设计并合成一系列新型非环核苷膦酸双L-氨基酸类化合物， 确定其结构， 并通过测定其对HepG2 2.2.15细胞分泌的HBV-DNA的抑制作用评价其体外抗病毒活性。结果发现8个adefovir双L-氨基酸类化合物可显示不同程度活性， 其中化合物11的抗病毒活性最强、 选择性指数最高(EC₅₀ 0.095 2 μmol·L^-1, SI 69523)。以上研究提示L-氨基酸酯策略可适用于非环核苷膦酸的前药修饰， 以期发现有效抗HBV药物。     

A new (E)-4-hydroxy-dodec-2-enedioic acid from the stem bark ofalbizzia julibrissin

A new unsaturated hydroxy acid was isolated from the stem bark extract of Albizzia julibrissin through repeated silica gel and Sephadex LH-20 column chromatography. The chemical structure of the new acid was determined as (E)-4-hydroxy-dodec-2-enedioic acid on the basis of several spectral data including 2D-NMR. The stereochemical feature of the double bond was determined to be E on the basis of the coupling pattern of related proton signals in the 1H-NMR and COSY experiments.     

凉粉草中熊果酸和齐墩果酸的提取工艺研究

目的 研究从凉粉草中提取熊果酸和齐墩果酸的工艺。方法 以高效液相色谱法测定熊果酸和齐墩果酸的含量,以两者含量之和为指标,通过对提取方法和提取温度进行单因素考察以及L9（34）正交法对提取条件进行优选。结果 凉粉草中熊果酸和齐墩果酸的最佳提取工艺采用回流提取法、温度80 ℃、95%乙醇、液料比14∶1、提取1次、每次1.5 h。结论 该工艺操作简单、易行,可提取得到含量较高的熊果酸和齐墩果酸。     

胡蔓藤生物碱的化学研究 Ⅱ.胡蔓藤碱丙(humantenidine)的化学结构

自马钱科(Loganiaceae)植物胡蔓藤(Gelsemium elegans Benth.)根的生物碱提取物中分离得到的一个新的氧化吲哚生物碱,命名为胡蔓藤碱丙(humantenidine),经光谱(UV,IR,¹HNMR,¹³CNMR,MS)分析和衍生物的制备,确定其化学结构为式(Ⅰ)所示     

桔梗中远志酸型皂苷的化学研究

目的分离、鉴定桔梗［Platycodon grandiflorum (Jacq.)A.DC］根中的远志酸型皂苷类化学成分。方法 采用乙醇提取、乙酸乙酯萃取，大孔树脂柱色谱、硅胶柱色谱及高效液相色谱等方法进行分离，得到3个化学成分，运用IR，MS，¹H NMR和¹³C NMR等光谱法鉴定化合物的结构。结果分离鉴定了3种三萜皂苷：3-O-β-D-laminaribiosyl polygalacic acid (I)，3-O-β-D-glucopyranosyl polygalacic acid (II)及polygalacin D (III)。结论化合物I是新化合物，II，III为已知化合物。化合物II为首次从该植物中分得，化合物I和II也是首次从桔梗中分离得到的单糖链糖苷。     

PAF antagonistic activity of 2-hydroxy-3-methoxybenzoic acid glucose ester fromGentiana scabra

In order to find out anti-platelet activating factor (PAF) from natural resources, Korean medicinal plants used for the treatments of peripheral circulation disorders were tested for their possible protective effects on PAF-induced anaphylactic shock. From the above screening, the methanol extract ofGentiana scabra showed a potent antagonistic activity against PAF. Water suspension of the extract was partitioned with CH₂Cl₂ and EtOAc, successively. The EtOAc fraction which showed the highest activity was chromatographed on silica gel to yield 6 fractions. From the fraction which showed higher PAF-antagonistic activity than the other fractions, compound1 was isolated by recrystallization. On the basis of spectral data, compound1 was identified as 2-hydroxy-3-methoxybenzoic acid glucose ester. The compound prevented the mice from the PAF-induced death at a dose of 300 μg/mouse.     

Protective effect of caffeic acid phenethyl ester on tert-butyl hydroperoxide-induced oxidative hepatotoxicity and DNA damage

Increased oxidative stress and associated high levels of free radical generation have been described to occur during the pathogeneses of various diseases in animal models. In the present work, we investigated the protective effects of the phenethyl ester of caffeic acid (CAPE), an active component of honeybee propolis, on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in a cultured HepG2 cell line and in rat liver. CAPE was found to significantly reduce t-BHP-induced oxidative injury in HepG2 cells, as determined by cell cytotoxicity, and lipid peroxidation and reactive oxygen species (ROS) levels in a dose-dependent manner. Furthermore, CAPE protected HepG2 cells against t-BHP-induced oxidative DNA damage, as determined by the Comet assay. Consistently, CAPE reduced hydroxyl radical-induced 2-deoxy-d-ribose degradation by ferric ion-nitrilotriacetic acid and H2O2, and also removed the superoxide anion generated by a xanthine/xanthine oxidase system. Our in vivo study showed that pretreatment with CAPE prior to the administration of t-BHP significantly and dose-dependently prevented increases in the serum levels of hepatic enzyme markers (alanine aminotransferase and aspartate aminotransferase) and reduced lipid peroxidation in rat liver. Moreover, histopathological evaluation of livers consistently revealed that CAPE reduced liver lesion induction by t-BHP. Taken together, these results suggest that the protective effects of CAPE against t-BHP-induced hepatotoxicity may, at least in part, be due to its ability to scavenge ROS and protect DNA from oxidative stress-induced damage.     

高效液相色谱法测定石见穿中齐墩果酸及熊果酸的含量

目的建立高效液相色谱法对中药石见穿中的熊果酸及齐墩果酸进行含量测定。方法采用高效液相色谱法,色谱柱Agilent HC18(4.6 mm×250 mm,5μm),流动相A相为0.1%甲酸水溶液,B相为甲醇,A∶B=14∶86,流速为1.0ml/min,柱温20℃,紫外检测波长205 nm,进样量50μl,运行时间为35 min。结果熊果酸和齐墩果酸能够达到基线分离,二者分别在11.55～462.0、5.265～210.6μg/ml,呈良好的线性关系,日内、日间精密度均小于5%(n=3),平均回收率分别为100.47%(RSD=1.95%,n=6)、101.88%(RSD=2.98%,n=6)。结论该法简便、快捷,结果准确、重复性好,可用于石见穿中熊果酸和齐墩果酸的质量控制。     

A new naphthalenepropanoic acid analog from the marine-derived actinomycetes Micromonospora sp. HS-HM-036

A new naphthalenepropanoic acid analog (1) was isolated from the broth of the actinomycetes Micromonospora sp. HS-HM-036. The structure of compound 1 was determined based on MS and extensive NMR analysis. A preliminary investigation of the biological activity of compound 1 was also described.     

A triterpene glucosyl ester from the roots ofRubus crataegifolius

Along with five known triterpene glycosides, a new triterpene glucosyl ester, named crataegioside, was isolated from the roots of Rubus crataegifolius Bunge. The structure was established as ilexosapogenin A 28-O-beta-D-glucopyranosyl ester by chemical and spectroscopic methods.     

Safety evaluation of arachidonic acid rich Mortierella alpina biomass in albino rats—A subchronic study

Safety evaluation of arachidonic acid rich Mortierella alpina biomass was carried out in Wistar rats by acute and subchronic oral toxicity studies. A preliminary acute toxicity study revealed that the biomass was safe at acute doses and that the LD50 exceeded 5000 mg/kg BW, the highest dose used in the study. In subchronic study, rats were fed diet containing 0, 2500, 5000, 10,000, 20,000 and 30,000 mg/kg, M. alpina biomass for a period of 13 weeks. Results indicated that biomass fortification had a positive influence on growth with no overt toxic effects on the survival, food consumption and body weight gain throughout the treatment interlude. The statistically significant changes in relative organ weights, serum biochemical and hematological indices in M. alpina fed groups’ viz., higher relative weights of spleen, liver, brain and ovary in females, reduced hemoglobin concentration in males, elevated WBC counts at highest dose, reduction in serum triglycerides and increased alkaline phosphatase activity were not concomitant with pertinent histopathological changes and hence toxicologically inconsequential. No microscopic or macroscopic lesions attributable to the treatment were manifested in the experimental groups. The results of the present study strongly advocate the safety of M. alpina biomass in rats at levels used in the study.     

13-Hydroxy-9Z,11E,15E-octadecatrienoic acid from the leaves of Cucurbita moschata

A new unsaturated hydroxy fatty acid was isolated from the leaves of Cucurbita moschata through repeated silica gel column chromatography and chemical methods. The structure of the new fatty acid was determined as 13-hydroxy-9,11,15-octadecatrienoic acid on the basis of several spectral data including 2D-NMR. The stererostructures of double bonds were determined to be 9Z, 11E and 15E by coupling patterns of related proton signals in the 1H-NMR and NOESY experiments.