Epigallocatechin-3-Gallate Protects against Homocysteine-Induced Brain Damage in Rats.

High levels of homocysteine are implicated in many neurovascular and neurodegeneration diseases. Epigallocatechin 3-gallate (EGCG), one of green tea polyphenols, has potential anti-oxidative and anti-inflammatory activities. However, it has not been explored whether EGCG has an effect on homocysteine-induced neuro-inflammation and neurodegeneration. In this study, we investigated the effects of EGCG on memory deficit, oxidative stress, neuro-inflammation, and neurodegeneration in hyper-homocysteinemic rats after a 2 wk homocysteine injection by vena caudalis. We found that supplementation of EGCG could rescue deficit of spatial memory induced by homocysteine. Treatment of EGCG significantly reduced the expression of malondialdehyde, glial fibrillary acidic protein, tumor necrosis factor-α, and interleukin-1ß and increased glutathione level in the homocysteine-treated group. In TdT-mediated dUTP nick end labeling (TUNEL) assay and Fluoro-Jade B staining, supplementation of EGCG could attenuate the apoptotic neurons and neurodegeneration. Interestingly, EGCG significantly ameliorated homocysteine-induced cerebrovascular injury. Our data suggest that EGCG could be a promising candidate for arresting homocysteine-induced neurodegeneration and neuro-inflammation in the brain.

Antifeedant activity of spin-labeled derivatives of deoxypodophyllotoxin against Brontispa longissima larvae.

To continue our search for natural product-based compounds for the control of Brontispa longissima larvae, eight spin-labeled podophyllotoxin derivatives (4a-h) and the intermediates 2 and 3 were tested for their insect antifeedant activity against third-instar larvae of B. longissima. Among all the tested compounds, 4a, 4c, 2 and 3 showed pronounced antifeedant activities with AFC50 values of 0.16, 0.31, 0.15 and 0.28 mg/mL, respectively. The different antifeedant activity ranges of these compounds indicated that variation of the structures of L-amino acids in these compounds markedly affected the activity profiles of this compound class, and some important SAR information has been revealed from it.

Anxiolytic and sedative effects of dehydroeffusol from Juncus effusus in mice.

Dehydroeffusol, a phenanthrene isolated from Juncus effusus L., possesses characteristic anxiolytic and sedative properties, as determined by an array of behavioral tests in mice. In the elevated plus-maze test, dehydroeffusol significantly increased the number of entries into the open arms and the time the mice spent in these arms in a dose-dependent manner, with a minimum effective dose of 2.5 mg/kg. Dehydroeffusol also significantly increased the head-dips of mice in the hole-board test in a dose-dependent manner, with a minimum effective dose of 5 mg/kg. Dehydroeffusol reduced mouse locomotion in the open-field test with a minimum effective dose of 5 mg/kg. In the rota-rod test, 1-5 mg/kg dehydroeffusol did not decrease the fall-down time of mice. The above results confirm that dehydroeffusol possesses anxiolytic and sedative properties and does not affect the general movement coordination of mice. This suggests that dehydroeffusol is a novel anxiolytic chemical derived from herbal medicines.

Design, synthesis and biological evaluation of novel spin-labeled derivatives of podophyllotoxin.

In order to design new antitumor drugs and study the relationship between antitumor and anti-oxidative activity of spin-labeled derivatives of podophyllotoxin, five novel pyrroline spin-labeled 4beta-N-substituted-amino acid-4'-O-demethylepipodophyllotoxin compounds (11a-e) (Scheme 2) were synthesized and evaluated. Their cytotoxicity against three tumor cell lines (human lung carcinoma A-549, human leukemia cell HL-60 and multiple myeloma RPMI-8226) has been evaluated using a MTT-based assay in vitro. Also, we determined malondialdehyde (MDA) in liver and kidney homogenate of SD rats by the TBA method. The five new compounds showed either superior or comparable inhibitory activity against A-549, HL-60 and RPMI-8226 cell lines compared with etoposide (VP-16, 2), and all the tested compounds showed more significant antioxidant activities than VP-16. Furthermore, the partition coefficients were measured and preliminary structure-activity relationships are presented.

First synthesis and biological evaluation of novel spin-labeled derivatives of deoxypodophyllotoxin.

Deoxypodophyllotoxin inhibits tubulin polymerization and induces cell cycle arrest at G2/M, followed by apoptosis. In order to find compounds with superior bioactivity and less toxicity, a series of spin-labeled derivatives of deoxypodophyllotoxin were synthesized by reacting 4'-demethyl-4-deoxypodophyllotoxin (DPPT) with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl) amino acids. The cytotoxic activities against three tumor cell lines (HL-60, RPMI-8226, A-549) in vitro and the antioxidative activities in tissues of Sprague Dawley (SD) rats of target compounds were evaluated, and the results indicated that compounds 11a-h were more potent in terms of cytotoxicities and antioxidative activities than either parent compound DPPT or anticancer drug VP-16.

The phenylpropanoids of Aster flaccidus.

Aster flaccidus bge has been used as traditional medicine in northwestern China. Two new phenylpropanoids (1-2) including one lignan: (7'R, 8S)-9'-lariciresinol-(alpha-methyl)-butanoate (1), 5,9-dimethoxyl-7-(alpha-methyl)-butanoxyl-phenyl-2E-propenol-(alpha-methyl)-butanoate (2) isolated from the chloroform extract of the root of Aster flaccidus bge were identified by means of extensive spectroscopic studies: 1D and 2D NMR spectra as well as HRMS analysis. They have not obvious anti-HIV-1 therapeutic activity (TI=1.0-1.1) compared with AZT (TI=55,556) as the result of the determination of their in vitro anti-HIV-1 activity while compound 2 displays strong antitumor activity against BEL 7402 (human liver carcinoma) with cisplatin as a positive control and the effect increases with the measuring-time going on (24 h, IC(50): 106.67+/-8.47 microM - 72 h, IC(50): 50.51+/-6.11 microM).

[Study on steroids of Cacalia tangutica].

Seven steroids and two cumarins were isolated from the petroleum ether extract of the specie Cacalia tangutica of the family Compositae which were collected in Minhe county, Qinhai province of China. The structures were identified as Stigmast4-en-3beta, 6beta-diol (1), 24-ethyl-5alpha-cholestane-3beta, 5, 6beta-triol (2), 7beta- methoxy-stigmast-5-en-3beta-ol (3), Schleicherastatin 1 (4), Stigmast-5-en-3beta, 7alpha-diol (5), umbelliferone (6) and hydrangetin (7) by the means of chemical and modern spectroscopic analysis (MS, 1H-NMR, 13C-NMR, DEPT). The compounds 1-5 were isolated from Cacalia tangutica for the first time.

[Phenolic components from Rhodiola dumulosa].

Eight phenolic compounds (1-7) were isolated from the methanol extract of the root of Rhodiola dumulosa. Their structures were identified as kaemperol (1), Quercetin (2), Gallic acid (3), (+) -Isolariciresinol-3alpha-O-beta-D-glucopyranoside (4), (-)-Isolariciresinol-3alpha-O-beta-D-glucopyra-noside (5), kaemperol-3-O-beta-D-glucopyranoside-7-alpha-O-L-rhamnoside (6), rutin (7) respectively on the basis of chemical and spectroscopic evidence. The compounds 3-7 were isolated from R. dumulosa for the first time.

The structure of an iridoid glycoside, 8-deoxyshanzhiside, from Lamiophlomis rotata.

8-deoxyshanzhiside was extracted from Lamiophlomis rotata (Benth.) Kudo. Extensive NMR spectroscopy techniques were used to fully assign the (1)H and (13)C spectra. X-ray investigation was used to identify its conformation, and absolute configuration.

Synthesis and insecticidal activities of novel derivatives of podophyllotoxin.

In order to find the biorational pesticides, eight novel 4beta-substituted phenoxyaniline derivatives of podophyllotoxin (4a-h) have been synthesized with significant stereoselectivity and improved yields by employing the BF(3).Et(2)O/NaI reagent system and evaluated for insecticidal activity against Pieris rapae as well as for their antifeedant effect against fifth instar larvae of P. rapae. The results showed that all these derivatives of PPT showed delayed insecticidal activity, which is different from the traditional neurotoxic insecticides. Among them, compounds possessing a 4beta-phenoxyaniline moiety substituted at para (CO(2)C(2)H(5), Cl, and OH) position exhibited greater insecticidal activity against P. rapae than podophyllotoxin. Also, the antifeedant activities showed that these compounds exhibited less potency than podophyllotoxin.

Design, synthesis, and biological evaluation of novel spin-labeled derivatives of podophyllotoxin as potential antineoplastic agents. Part XII.

Five novel nitroxyl spin-labeled ester derivatives of podophyllotoxin (11a-11e) have been prepared and their structural information on these nitroxyl spin-labeled ester derivatives of podophyllotoxin (11a-11e) using (1)HNMR spectroscopy was efficiently obtained by application of the in situ reduction of representative nitroxyl spin-labeled ester derivative of podophyllotoxin 11e with phenylhydrazine for the preparation of N-hydroxylamine 12 in the NMR tube. These novel derivatives were further evaluated for their in vitro cytotoxic activity against five neoplastic cell lines (K562, HL-60, SPCA-1, Lewis, and L-1210) using MTT assay. Most of the target compounds (except for all these compounds against SPCA-1) exhibited more pronounced cytotoxicity against several neoplastic cell lines than that of the prototypical inhibitor etoposide.

[Study on extraction methods of activity components from Podophyllum emodi wall].

Supercritical fluid Extraction (SFE) with subsequent HPLC analysis was utilized to extract activity components such as podophyllotoxin, deoxypodophyllotoxin, kaempferol and quercetin from the roots and stems of Podophyllum emodi Wall. The extraction yields obtained by SFE were compared to those obtained by organic solvent extraction and were found to be comparable or lower. In addition, we used the orthogonal experiment which conducts with 3 factors and 4 levers in order to find the best dynamic extraction conditions.

[Content deternmination of glycyrrhizic acid in cortex glycyrrhizae].

Glycyrrhizic acid content in Fen Gancao (barked licorice root) and its rough bark (Cortex Glycyrrhizae) was determined by HPLC. The result showed that at least three unknown ingredients were detected in Cortex Glycyrrhizae which were not in Fen Gancao, and glycyrrhizic acid content in the Cortex Glycyrrhizae is higher than that in Fen Gancao. It suggests that Cortex Glycyrrhizae can be used as the material not only to extract glycyrrhizic acid but also for making additives. Furtheronore, Fen Gancao should be further studied in order to reveal the differences of pharmacological effects between Fen Gancao and Licorice Root (Radix Glycyrrhizae).

Insecticidal activity of deoxypodophyllotoxin, isolated from Juniperus sabina L, and related lignans against larvae of Pieris rapae L.

In the course of screening for naturally occurring insecticides from plants from the northwestern part of China, a petroleum ether extract of Juniperus sabina L was found to show insecticidal activity against fifth-instar larvae of Pieris rapae L. From the extract, an insecticidal compound was isolated by bioassay-guided fractionation. The compound was identified as deoxypodophyllotoxin (1) by comparison of its spectroscopic characteristics with literature data. In bioassays, 1 showed antifeedant activity against fifth-instar larvae of P rapae at 0.05-1.00 g litre(-1) and its AFC50 (concentration for 50% antifeedant activity) values at 12 and 48h were 0.170 and 0.060 g litre(-1), respectively. In that concentration range, all treated insects died within 48 h after treatment and compound 1 showed delayed insecticidal activity. At 0.015-0.100 g litre(-1), 1 showed insecticidal activity, with an LC50 of 0.020 g litre(-1). The related compound deoxypicropodophyllotoxin (2), however, showed lower antifeedant and insecticidal activities than 1 in bioassay. This indicated that the trans-lactone ring is an important moiety for enhancing activity in these compounds. Comparison of the insecticidal activities of 1 and another related compound, podophyllotoxin (3), suggested that varying the substituent at C-4 is an exciting possibility for synthesizing more potent analogues.

Six new sesquiterpenes from Euonymus nanoides and their antitumor effects.

Six new dihydro-beta-agarofuran [5,11-epoxy-5beta,10alpha-eudesm-4 (14)-ene] sesquiterpenes were isolated from the seeds of Euonymus nanoides Loes, including five with a novel substitution pattern: (1 R,2 S,4 S,5 R,7 R,9 S,10 R)-1alpha-benzoyloxy-2alpha,15-diacetoxy-4beta-hydroxy-9beta-cinnamoyloxy-beta-dihydroagarofuran ( 1), 1alpha-(alpha-methyl)-butanoyl-2alpha,15-diacetoxy-4beta-hydroxy-9beta-(beta-)furoyloxy-beta-dihydroagarofuran ( 2), 1alpha,2alpha-di-(alpha-methyl)-butanoyl-4beta-hydroxy-9beta-(beta-)furoyloxy-15-acetoxy-beta-dihydroagarofuran ( 3), 1alpha-(alpha-methyl)-butanoyl-2alpha-(alpha-methyl)-propynoyloxy-4beta-hydroxy-9beta-(beta-)furoyloxy-15-acetoxy-beta-dihydroagarofuran ( 4) and 1alpha,2alpha, 9beta-tri-(beta-)furoyloxy-4beta-hydroxy-15-acetoxy-beta-dihydroagarofuran ( 5). The other dihydroagarofuran sesquiterpene was 1alpha,2alpha,6beta,15-tetraacetoxy-3alpha-(alpha-methyl)-butanoyl-4beta-hydroxy-9beta-(beta-)furoyloxy-beta-dihydroagarofuran ( 6). The structures of 1 - 6 were elucidated by means of (1)H- and (13)C-NMR spectroscopic studies, including 2D heteronuclear COSY (HMQC), long-range correlation spectra with inverse detection (HMBC), (1)H- (1)H COSY and NOESY. The absolute configuration of compound 1 was determined by application of the CD exciton chirality method. Six compounds were evaluated for their in vitro antitumor effects (IC (50) values: 27.71 - 50.69 microg/mL) and the structure-activity relationship is discussed.

[Applications of solid-phase microextraction technique in natural product analysis].

Solid-phase microextraction is a new technique of analysis. It has many merits and expanse foreground. A Review of the principle, recent development and applications of solid-phase microextraction is given, focusing on natural product analysis, especially on Chinese traditional medicine. Twenty-nine references are cited in the paper.

Insecticidal compounds from Tripterygium wilfordii active against Mythimna separata.

In the course of screening for novel naturally occurring insecticides from plants, the ethanol extract of the root bark of Tripterygium wilfordii Hook f. was found to show insecticidal activity against larvae of Mythimna separata Walker. Three active compounds were isolated by bioassay-guided fractionation of the extract and characterized as triptolide (1), triptonide (2) and euonine (3) by IR, 1H and 13C NMR and mass spectral analysis. Compounds 1 and 2 showed strong contact activity against 3rd or 5th larvae of M. separata (LD50 1.6 microg/insect for 1, 2.9 microg/insect for 2, no contact activity for 3; LD50 is the lethal dose for 50% mortality). The antifeedant activity against the 3rd larvae of M. separata after a 24-h treatment was demonstrated; 1, 2 and 3 gave EC50 (effective concentration causing 50% antifeedance) values of 0.25, 0.35 and 0.02 mM, respectively. 1 and 2 were inferior to the positive control represented by toosendanin (12a-acetoxyamoorastatin), 3 was superior to toosendanin. For the ingested toxicity against M. separata, 1 had the more potent activity with an KD50 value of 13.5 microg/g (insect body weight) than toosendanin. This is the first report on insecticidal activity of these three compounds.

Applications of solid-phase microextraction technique in natural product analysis / 中国中药杂志

Solid-phase microextraction is a new technique of analysis. It has many merits and expanse foreground. A Review of the principle, recent development and applications of solid-phase microextraction is given, focusing on natural product analysis, especially on Chinese traditional medicine. Twenty-nine references are cited in the paper.

Antioxidative activity of spin labeled derivatives of podophyllic acid hydrazide.

AIM: To study the relationship between structure and antioxidation activity of spin labeled derivatives of podophyllic acid hydrazide (GP) in tissues and red blood cells (RBC) from rats. METHODS: The homogenate of liver, heart, and kidneys of rats was used to measure malondialdehyde (MDA) spontaneous generated and induced by hydroxyl free radical generation system (Fe2+-ascorbic acid, FRGS) or doxorubicin (DOX) by TBA colorimetric method. H2O2-caused hemolysis was determined spectrophotometrically. Superoxide anion from zymosan-stimulated neutrophils of rats was evaluated by NBT-reduction assay. RESULTS: GP1 and GP1OH obviously inhibited MDA formation either spontaneously or induced by FRGS and DOX and antagonized hemolysis induced by H2O2, but GP and GP1H showed less potent activity. GP1 also inhibited the formation of superoxide anion from activated neutrophils of rats. CONCLUSION: Introduction of nitroxyl radical moieties into GP generated potent derivatives with antioxidative activity. The essential antioxidation active groups of spin labeled derivative of GP are NO or NOH group in nitroxyl radical moieties.

[The changes of some chemical components in banxiaxiexintang decoction of different combinations].

OBJECTIVE: The contents of bererine, palmatine and glycyrrhizin acid in Banxiaxiexintang decoction of different combinations were determined by PR-HPLC. METHOD: A Shim-pack CLC-ODS column was used with a mobile phase of CH3CN-H2O (31:69; 0.005 moL.L-1 -pentanesulfonic acid sodium salt, H3PO4: pH 3.0) for bererine andpalmatine, which were detected at the wavelength of 275 nm. A YWG-C18 column was used with a mobile phase of CH3OH-H2O-HAc(62:37:1) for glycyrrhizin acid which was detected at the wavelength of 260 nm. RESULT: Each herbs' combination influences the contents of the 3 components. CONCLUSION: The experiment is an attempt to study the comical foundation of traditional Chinese prescription.