Biomedical subjects

Dean Guo

Publications and source records attributed to Dean Guo.

52 records · Page 3Linked to original sources

PubMed2004

Structure-activity relationships of saponins from Gleditsia sinensis in cytotoxicity and induction of apoptosis.

Thirteen compounds were isolated from the anomalous fruits of Gleditsia sinensis on the basis of bioassay-guided fractionation. These saponins together with six analogues or related compounds were tested for their cytotoxicities against six tumor cell lines by the MTT method. The induction of apoptosis in HL-60 cells by these compounds was determined through flow cytometric analysis. Some structure-activity relationships in cytotoxicity and induction of apoptosis were identified. The evaluation of the cytotoxicity and the ability to induce apoptosis revealed that some important structural features are required for activity. A valuable model which enables prediction of their activities was established and may be employed for the drug design of new Gleditsia saponin analogues.

Antineoplastic Agents, Phytogenic↗

PubMed2004

Analysis of strychnine and brucine in postmortem specimens by RP-HPLC: a case report of fatal intoxication.

A sensitive method for the identification and quantitation of the toxic alkaloids strychnine and brucine from postmortem specimens has been established. After solid-phase extraction using Oasis MCX cartridges the extracts were analyzed by high-performance liquid chromatography with diode-array detection. The limit of detection was 0.5 ng/mL blood for strychnine and brucine, and the limit of quantitation was 5 ng/mL blood for strychnine and brucine. The method was applied for the analysis of blood and gastric contents of a 34-year-old female who died after ingestion of a packet of herbal medicine powder containing the seeds of Strychnos nux-vomica L. Strychnine and brucine were detected in all the samples. The concentration in our case is consistent with that in previous reports.

Adult↗

PubMed2004

Specific 12 beta-hydroxylation of cinobufagin by filamentous fungi.

Biotransformation of natural products has great potential for producing new drugs and could provide in vitro models of mammalian metabolism. Microbial transformation of the cytotoxic steroid cinobufagin was investigated. Cinobufagin could be specifically hydroxylated at the 12 beta-position by the fungus Alternaria alternata. Six products from a scaled-up fermentation were obtained by silica gel column chromatography and reversed-phase liquid chromatography and were identified as 12 beta-hydroxyl cinobufagin, 12 beta-hydroxyl desacetylcinobufagin, 3-oxo-12 beta-hydroxyl cinobufagin, 3-oxo-12 beta-hydroxyl desacetylcinobufagin, 12-oxo-cinobufagin, and 3-oxo-12 alpha-hydroxyl cinobufagin. The last five products are new compounds. 12 beta-Hydroxylation of cinobufagin by A. alternata is a fast catalytic reaction and was complete within 8 h of growth with the substrate. This reaction was followed by dehydrogenation of the 3-hydroxyl group and then deacetylation at C-16. Hydroxylation at C-12 beta also was the first step in the metabolism of cinobufagin by a variety of fungal strains. In vitro cytotoxicity assays suggest that 12 beta-hydroxyl cinobufagin and 3-oxo-12 alpha-hydroxyl cinobufagin exhibit somewhat decreased but still significant cytotoxic activities. The 12 beta-hydroxylated bufadienolides produced by microbial transformation are difficult to obtain by chemical synthesis.

Alternaria↗

PubMed2004

Gleditsia sinensis fruit extract induced growth inhibition involves basic fibroblast growth factor and nitric oxide.

Recently we have shown the antiproliferative activity of Gleditsia sinensis fruit extract (GSE) on various solid tumour and leukaemia cell lines as well as primary cultured bone marrow cells isolated from patients with acute and chronic myelogenous leukaemia. We further studied whether the growth inhibitory effect of GSE involves basic fibroblast growth factor (bFGF) in cancer cell lines including breast cancer MDA-MB231, nasopharyngeal cancer CNE-2 and prostate cancer LNCaP. We also investigated whether GSE could alter the production of nitric oxide (NO) pattern from these cancer cell lines. Growth inhibition assay was quantitated by sulforhodamine B protein staining method. Enzyme linked immunosorbent assay (ELISA) was used to quantitate the total bFGF protein. The amount of NO secreted into culture medium in terms of nitrite ion concentration was measured by the Greiss method. ELISA showed that GSE could stimulate total bFGF protein level which was dose- dependent. NO production was also stimulated from these cancer cell lines after treating with GSE. Both of the increment in total bFGF and NO levels were correlated with the degree of growth inhibition. Changes involving cell shrinkage and detachment of cancer cells could readily be observed. Taken together, our results here suggest that growth inhibition induced by GSE in these solid tumour cell lines may involve both bFGF and NO regulations.

Fibroblast Growth Factor 2↗

PubMed2003

Substrate specificity for the hydroxylation of polyoxygenated 4(20),11-taxadienes by Ginkgo cell suspension cultures.

Three C-14 oxygenated taxanes isolated from callus cultures of Taxus spp., 2alpha,5alpha,10beta,14beta-tetra-acetoxy-4(20),11-taxadiene 3, 2alpha,5alpha,10beta-triacetoxy-14beta-propionyloxy-4(20),11-taxadiene 4, 2alpha,5alpha,10beta-triacetoxy-14beta-(2-methylbutyryl)-oxy-4(20),11-taxadiene 5, and three deacetylated derivatives of 3, 10beta-hydroxy-2alpha,5alpha,14beta-triacetoxy-4(20),11-taxadiene 6, 14beta-hydroxy-2alpha,5alpha,10beta-triacetoxy-4(20),11-taxadiene 7, 10beta,14beta-dihydroxy-2alpha,5alpha-diacetoxy-4(20),11-taxadiene 8, could all be regio- and stereo-selectively hydroxylated at the 9alpha-position by Ginkgo cell suspension cultures to yield a series of new 9alpha,14beta-dihydroxylated taxoids. The effects of functional groups, especially at C-14 of the substrates, on the biotransformation were also investigated. The results revealed that substrates with an acetoxyl group at C-14 could be more efficiently 9alpha-hydroxylated than those with a longer ester chain or a hydroxyl group at C-14. An acetoxyl or hydroxyl group at C-10 had no effect on the conversion rates of the substrates, but substrates with the hydroxyl group (compared with the acetoxyl analogues) could be converted into 9alpha-hydroxylated products more easily.

Alkenes↗

PubMed2003

Conyzasaponins I-Q, nine new triterpenoid daponins from Conyza blinii.

Nine new triterpenoid saponins, conyzasaponins I-Q (1-9), were isolated from the aerial parts of Conyza blinii. Their structures were established on the basis of extensive 1D and 2D NMR spectra as well as by chemical degradations. Among these compounds, conyzasaponins M-O (5-7) share a common pentasaccharide unit attached to C-28 of the aglycon, 28-O-beta-d-apiofuranosyl-(1-->3)-beta-d-xylopyranosyl-(1-->4)-[beta-d-apiofuranosyl-(1-->3)]-alpha-l-rhamnopyranosyl-(1-->2)-alpha-l-arabinopyranosyl ester, which contains two apiofuranosyl residues. To the best of our knowledge, they are among the few examples of natural products possessing two apiofuranose units in a single sugar chain.

Conyza↗

PubMed2003

Microbial transformation of ginsenoside Rb1 by Rhizopus stolonifer and Curvularia lunata.

Of 49 microbial strains screened for their capabilities to transform ginsenoside Rb1, Rhizopus stolonifer and Curvularia lunata produced four key metabolites: 3-O-[beta-D-glucopyranosyl-(1,2)-beta-D-glucopyranosyl]-20-O-[beta-D-glucopyranosyl]-3beta,12beta, 20(S)-trihydroxydammar-24-ene (1), 3-O-[beta-D-glucopyranosyl-(1,2)-beta-D-glucopyranosyl]-20-O-[beta-D-glucopyranosyl]-3beta,12beta, 20(S)-trihydroxydammar-24-ol (2), 3-O-[beta-D-glucopyranosyl-(1,2)-beta-D-glucopyranosyl]-3beta, 12beta, 20(S)-trihydroxydammar-24-ene (3), and 3-O-beta-D-glucopyranosyl-3beta, 12beta, 20(S)-trihydroxydammar-24-ene (4), identified by TOF-MS, 1H- and 13C-NMR spectral data. Metabolites 1, 3 and 4 were from the incubation with R. stolonifer, and 1 and 2 from the incubation with C. lunata. Compound 2 was identified as a new compound.

Ascomycota↗

PubMed2003

Neuroprotective effects of hydroxysafflor yellow A: in vivo and in vitro studies.

Previous work has shown that hydroxysafflor yellow A (HSYA), extracted from Carthamus tinctorius L. markedly extended the coagulation time in mice and exhibited a significant antithrombotic effect in rats. The present study was conducted to demonstrate further its neuroprotective effects on cerebral ischemic injury in both in vivo and in vitro studies. In vivo, male Wistar-Kyoto (WKY) rats with middle cerebral artery occlusion (MCAO) were evaluated for neurological deficit scores followed by the treatment with a single dose of HSYA. Furthermore, the infarction area of the brain was assessed in the brain slices. In vitro, the effect of HSYA was tested in cultured fetal cortical cells exposed to glutamate and sodium cyanide (NaCN) to identify its neuroprotection against neurons damage. The results in vivo showed that sublingular vein injection of HSYA at doses of 3.0 mg/kg and 6.0 mg/kg exerted significant neuroprotective effects on rats with focal cerebral ischemic injury by significantly decreasing neurological deficit scores and reducing the infarct area compared with the saline group, HSYA at a dose of 6.0 mg/kg showed a similar potency as nimodipine at a dose of 0.2 mg/kg. Sublingular vein injection of HSYA at the dose of 1.5 mg/kg showed a neuroprotective effect, however, with no significant difference when compared with the saline group. Results in vitro showed that HSYA significantly inhibited neuron damage induced by exposure to glutamate and sodium cyanide (NaCN) in cultured fetal cortical cells. Noticeably, the neuroprotective action of HSYA on glutamate-mediated neuron injury was much better than that of HSYA on NaCN-induced neuron damage. All these findings suggest that HSYA might act as a potential neuroprotective agent useful in the treatment in focal cerebral ischemia. Abbreviations. HSYA:hydroxysafflor yellow A TTC:2,3,5-triphenyltetrazolium chloride MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide DMEM:Dulbecco's modified Eagle medium FCS:Fetal calf serum MCAO:middle cerebral artery occlusion ECA:external carotid artery ICA:internal carotid artery LDH:lactate dehydrogenase NMDA: N-methyl- D-aspartate

Animals↗

PubMed2003

Induction of apoptosis and G2/M cell cycle arrest by Gleditsioside E from Gleditsia sinensis in HL-60 cells.

Gleditsioside E, a triterpene saponin isolated from Gleditsia sinensis, showed significant cytotoxicity against Bel-7402, BGC-823, HeLa, HL-60 and MCF-7 cell lines. The results of flow cytometry with annexin V-FITC/PI double staining proved that gleditsioside E mainly induced early apoptosis in HL-60 cells. Gleditsioside E treatment resulted in a prominent increase of the G 2 /M population in HL-60 cells, and an accumulation of the sub-G 1 (hypoploid) peak was observed.

Antineoplastic Agents, Phytogenic↗

PubMed2003

Cytotoxic biotransformed products from triptonide by Aspergillus niger.

The diterpenoid triepoxides are the major active constituents of Tripterygium wilfordii with potent antitumor and immune activities. But the strong toxicity of these compounds has restricted their application to a great extent. In order to find more effective compounds with less toxicity, structural modifications of triptonide (1) by Aspergillus niger (AS 3.739) were investigated and four biotransformed products were obtained. Based on their chemical and spectral data, their structures were elucidated as 5alpha-hydroxytriptonide (2), triptolide (3), 17-hydroxytriptonide (4), and 16-hydroxytriptonide (5), among which 2, 4 and 5 are new compounds. All the three new transformed products showed cytotoxic activities against the majority of the human tumor cell lines tested, however, they are found to possess less cytotoxic activity when compared with 1. Both compounds 4 and 5 showed similar cytotoxic activity and their IC (50) values were 5-15 fold less than 1, while 2 is about 100 times less active than 1.

Antineoplastic Agents, Phytogenic↗

PubMed2003

Anti-angiogenic potential of Gleditsia sinensis fruit extract.

Blood supply plays a crucial role in solid tumour development and leukaemogenesis. It has been suggested that blocking of angiogenesis could be possible in cancer therapy. We have demonstrated the antiproliferative activity of Gleditsia sinensis fruit extract (GSE) on various human solid tumour cancer cell lines as well as leukaemia cell lines and primary cultured leukaemia cells obtained from leukaemia patients. However, the antiangiogenic potential of GSE has not been demonstrated. Here we demonstrated that GSE could reduce vascular endothelial growth factor (VEGF) mRNA expression in dose- and time course-dependently in MDA-MB231 breast cancer and HepG2 hepatoblastoma cell lines as measured by reverse transcriptase polymerase chain reaction. Enzyme-linked immunosorbent assay further showed that GSE could reduce the VEGF secretion from various cancer cell lines including MDA-MB231, HepG2, HL-60 (acute promyelocytic leukaemia) and eleven primary cultured leukaemia cells obtained from acute myelogenous leukaemia patients. In vivo chick chorioallantoic membrane assay illustrated that GSE could reduce the angiogenic activity of basic fibroblast growth factor. Taken together, the information suggested that GSE could be potentially used as an angiogenic inhibitor in both solid tumour and leukaemia therapy.

Adult↗

PubMed2002

Biotransformation of 2alpha,5alpha,10beta,14beta-tetraacetoxy-4(20),11-taxadiene by cell suspension cultures of Catharanthus roseus.

Catharanthus roseus cell suspension cultures were employed for the biotransformation of 2alpha,5alpha,10beta,14beta-tetraacetoxy-4(20),11-taxadiene ( 1), and four metabolites were obtained. Based on their physical and chemical data, the structures of the four metabolites were respectively elucidated as 10beta-hydroxy-2alpha,5alpha,14beta-triacetoxy-4(20),11-taxadiene (2), 5alpha-hydroxy-2alpha,10beta, 14beta-triacetoxy-4(20),11-taxadiene (3), 6alpha,10beta-dihydroxy-2alpha,5alpha,14beta-triacetoxy-4(20),11-taxadiene (4), and 6alpha,9alpha,10beta-trihydroxy-2alpha,5alpha,14beta-triacetoxy-4(20),11-taxadiene (5), among which 3 and 5 were characterized as new taxoids. The effects of the stages of substrate addition on the biotransformation were also investigated. The results revealed that the biotransformation rate for 1 reached 85.3 % and the yield of 2 70 % when 1 was administered during the mid-linear phase (9 - 12 th day) of the cell growth cycle. On the other hand, the yield for 4 reached the highest level of 11.8 % when 1 was added in the early linear phase (6 th day).

Bioreactors↗

PubMed2002

Estrogen-like activity of ginsenoside Rg1 derived from Panax notoginseng.

Ginsenosides have demonstrated pharmacological effects in the central nervous, cardiovascular, and endocrine systems. We hypothesize that ginsenosides might mediate some of their actions by binding to the estrogen receptor, as they share many of the protective actions of estrogen in various physiological systems. The present study is aimed to determine whether ginsenoside Rg1 can act like an estrogen analog in stimulating human breast cancer cell growth as well as in the activation of estrogen response element-luciferase activity in HeLa cell. Rg1, but not its aglycone, stimulates [methyl-(3)H] thymidine incorporation in estrogen receptor-positive MCF-7 in a dose-dependent manner (10(-15)-10(-7) M). The stimulation of MCF-7 cell proliferation by 3 x 10(-13) M Rg1 can be blocked by 10(-6) M of the estrogen antagonist ICI 182780. Moreover, Rg1 stimulates estrogen response element-luciferase reporter gene activity in HeLa cells with an optimal dose of 3 x 10(-10) M. Such stimulation can also be blocked by 10(-6) M ICI 182780. In addition, Rg1 has no effect on [methyl-(3)H]thymidine incorporation in estrogen receptor-negative human breast cancer cells (MDA-MB-231). Furthermore, Rg1 failed to displace the specific binding of [(3)H]17 beta-estradiol to MCF-7 cell lysates, suggesting that no direct interaction of Rg1 with estrogen receptor is needed for its estrogenic action. Our results indicate that ginsenosides Rg1 has estrogen-like activity and should be classified as a novel class of potent phytoestrogen.

Breast Neoplasms↗

PubMed1998

Anthraquinones from hairy root cultures of Cassia obtusifolia.

Hairy root cultures of Cassia obtusifolia clones transformed with Agrobacterium rhizogenes strain 9402 were established to investigate the anthraquinone production. Seven anthraquinones, together with betulinic acid, stigmasterol and sitosterol were isolated from the hairy roots. Their chemical structures were elucidated on the basis of chromatographic and spectral data. The effects of culture conditions and rare earth element Eu(3+) on the production of six free anthraquinones have also been investigated. It was found that changes of the elements in the culture medium and addition of rare earth element Eu(3+) can greatly influence the contents of free anthraquinones in the hairy roots.

Journal Article↗

PubMedDate not supplied

The application of an artificial neural network in the identification of medicinal rhubarbs by near-infrared spectroscopy.

This paper describes a method to combine near-infrared spectroscopy and a three layer back-propagation artificial neural network in order to identify official and unofficial rhubarbs. Thirty-three samples were taken as the training set, and 62 samples as the test set. The effects of input node number, learning rate and momentum on the final error and recognition accuracy for the training set, and on prediction accuracy for the test set were determined. A neural network with eight input nodes, a 0.5 learning rate, and a momentum of 0.3 can achieve a recognition accuracy of 100% for the training set and a prediction accuracy of 96.8% for the test set. The method described offers a quick and efficient means of identifying rhubarbs.

Neural Networks, Computer↗

PubMedDate not supplied

Quantitative determination of Aconitum alkaloids in blood and urine samples by high-performance liquid chromatography.

An HPLC method has been developed for the simultaneous determination of the toxic Aconitum alkaloids, aconitine, mesaconitine and hypaconitine in blood and urine samples. The samples were initially subjected to solid phase extraction using Oasis MCX cartridges, and the alkaloids were separated on an XTerra RP18 column, gradient-eluted with acetonitrile: ammonium hydrogen carbonate buffer. Calibration curves were linear in the range 2.75-550 ng for aconitine and hypaconitine, and 3-600 ng for mesaconitine: the limit of detection was 0.1 ng (signal-to-noise ratio of 3) for each alkaloid. The described analysis proved to be sensitive, rapid and economical, and will be applied in the identification and determination of these alkaloids in forensic and therapeutic drug monitoring.

Aconitine↗