Biomedical subjects

D Y Zhu

Publications and source records attributed to D Y Zhu.

At least 19 recordsLinked to original sources

PubMed2006

Prostaglandin E2 regulates Foxo activity via the Akt pathway: implications for pancreatic islet beta cell dysfunction.

AIMS/HYPOTHESIS: Prostaglandin E(2) (PGE(2)) is a well-recognised inhibitor of glucose-stimulated insulin secretion (GSIS). The aim of this study was to investigate the signalling pathway of PGE(2) in beta cell function regulation in HIT-T15 cells and isolated rat islets. MATERIALS AND METHODS: mRNA levels of the prostaglandin E receptor 3 (Ptger3) were measured by real-time PCR. Western blot analysis was used to detect changes in the levels of PTGER3, phosphorylated and total Akt, phosphorylated and total forkhead box 'Other' (Foxo). Transient transfection and reporter assays were used to measure Foxo transcriptional activity. The biological significance of PGE(2) in beta cell function was analysed using MTT, flow cytometry and GSIS assays. RESULTS: We found that treating HIT-T15 cells with exogenous PGE(2) stimulated Ptger3 gene expression specifically, and diminished cAMP generation. These were accompanied by the downregulation of Akt and Foxo phosphorylation in HIT-T15 cells and isolated rat islets. Moreover, PGE(2) upregulated basal and partially reversed constitutively active Akt-inactivated Foxo transcriptional activity. Furthermore, GSIS was impaired in PGE(2)-treated HIT-T15 cells and isolated islets. However, the dosage used in the above experiments did not affect beta cell viability and apoptosis. In addition, insulin-like growth factor 1 (IGF-1) pretreatment reversed the effects of PGE(2), and wortmannin treatment abolished the preventive effects of IGF-1. CONCLUSIONS/INTERPRETATION: Our observations strongly suggest that PGE(2) can induce pancreatic beta cell dysfunction through the induction of Ptger3 gene expression and inhibition of Akt/Foxo phosphorylation without impacting beta cell viability. These results shed light on the mechanisms of PGE(2) actions in pancreatic beta cell dysfunction.

Androstadienes↗

PubMed2006

Neuronal nitric oxide synthase-derived nitric oxide inhibits neurogenesis in the adult dentate gyrus by down-regulating cyclic AMP response element binding protein phosphorylation.

Neuronal nitric oxide synthase, the major nitric oxide synthase isoform in the mammalian brain, is implicated in some developmental processes, including neuronal survival, precursor proliferation and differentiation. However, reports about the role of neuronal nitric oxide synthase in neurogenesis in the adult dentate gyrus are conflicting. Here we show that 5-bromodeoxyuridine-labeled dividing progenitor cells in the dentate gyrus were significantly increased in mice receiving 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, and in null mutant mice lacking neuronal nitric oxide synthase gene (nNOS-/-) 6 h and 4 weeks after 5-bromodeoxyuridine incorporation. The increase in 5-bromodeoxyuridine positive cells in 7-nitroindazole-treated mice was accompanied by activation of cyclic AMP response element binding protein phosphorylation in the dentate gyrus. Pretreatment with N-methyl-D-aspartate receptor antagonist MK-801 fully abolished the effects of 7-nitroindazole on neurogenesis and cyclic AMP response element binding protein phosphorylation. Furthermore, neuronal nitric oxide synthase inhibition significantly enhanced the survival of newborn cells and the number of 5-bromodeoxyuridine positive/NeuN positive cells in the dentate gyrus. These results indicate that neuronal nitric oxide synthase-derived nitric oxide suppresses neurogenesis in the adult dentate gyrus, in which N-methyl-D-aspartate receptor functions and cyclic AMP response element binding protein phosphorylation may be involved.

Animals↗

PubMed2001

Inhibition of stress-activated protein kinase in the ischemic/reperfused heart: role of magnesium tanshinoate B in preventing apoptosis.

The activation of stress-activated protein (SAP) kinase may lead to an induction of apoptosis that is responsible for part of the cardiomyocyte death in reperfusion injury. The objective of the present study was to investigate the mechanism by which magnesium tanshinoate B (MTB), a bioactive compound isolated from Danshen, prevents apoptosis in cardiomyocytes in the ischemic/reperfused heart. Isolated adult rat hearts were perfused by the Langendorff mode with medium containing MTB prior to the induction of normothermic global ischemia. At the end of the 30-min ischemic period, the heart was reperfused with the same medium with or without MTB for an additional 20 min. In the MTB-treated ischemic/reperfused heart, the number of apoptotic nuclei was reduced by 2.5-fold in comparison to that in untreated ischemic/reperfused controls [23 +/- 4 vs 57 +/- 7 (mean +/- SD) TUNEL-positive cells, respectively, N = 3-4, P < 0.001]. SAP kinase activity was elevated 1.7-fold in ischemic/reperfused rat hearts [35.6 +/- 3.8 vs 21.2 +/- 3.3 (control) (mean +/- SEM) relative densitometric units, N = 4-6, P < 0.05]. Treatment with MTB abolished this elevation in SAP kinase activity (25.0 +/- 5.2 relative densitometric units), which was also decreased by 40% in the nucleus. When the heart was subjected to ischemia alone, there was no significant change in SAP kinase activity in the presence or absence of MTB. MTB did not appear to affect the p38 mitogen-activated protein kinase activity in this model system. In conclusion, MTB was shown to have cardioprotective activity against apoptosis, probably through the inhibition of SAP kinase activity.

Animals↗

PubMed2001

Furanochromone radical cations: generation, characterization and interaction with DNA.

The radical cations of naturally occurring furanochromones visnagin (VI) and khellin (KH) have been generated and identified for the first time by use of laser flash photolysis and pulse radiolysis techniques. The lifetimes of VI(.+) and KH(.+) are determined as approximately 6 and approximately 35 micros under these conditions, respectively. Direct 308-nm excitation of VI in aqueous buffer at physiological pH results in monophotonic photoionization to generate VI(.+), with a quantum yield of 0.075, which is much higher than that of 8-methoxypsoralen and KH under identical conditions. Though VI(.+) is a more powerful oxidant than KH(.+), both of them react with guanosine mononucleotide (k=1.2x10(9) and 3.8x10(7) dm(3) mol(-1) s(-1), respectively) via electron transfer to give the guanine radical cation. Furthermore, selective oxidation of guanine in single and double strand DNA by VI(.+) was also observed. These novel findings suggest that electron transfer reactions involving furanochromone radical cations may be of considerable importance in furanochromone photochemotherapy.

Cations↗

PubMed2001

Magnesium tanshinoate B (MTB) inhibits low density lipoprotein oxidation.

Danshen, a Chinese herbal medicine has been widely used for the treatment of cardiovascular diseases. Magnesium tanshinoate B (MTB) is an active compound purified from Danshen. The objective of this study was to investigate the effect of MTB on the susceptibility of low density lipoproteins (LDL) to oxidative modification as well as on the accumulation of lipids in THP-1 derived macrophages. Aliquots of LDL were incubated with copper sulfate in the absence or presence of MTB. The degrees of oxidative modification of LDL were assessed by examining the relative gel electrophoretic mobility, by measuring the amount of thiobarbituric acid reactive substances (TBARS), and by continuous monitoring of the formation of conjugated dienes upon the increase in absorbency at 234 nm. MTB at concentrations of 1-10 microM significantly inhibited oxidative modification of LDL. Such inhibitory effect resulted in a decrease in the uptake of LDL by THP-1 derived macrophages. Taken together, these results clearly demonstrate that MTB inhibits oxidative modification of LDL and hence prevents the uptake of LDL by cultured macrophages. Such effect may be therapeutically relevant in protecting cells from lipid peroxidation in vascular disorders.

Adult↗

PubMed2001

Authentic identification of stigma Croci (stigma of Crocus sativus) from its adulterants by molecular genetic analysis.

Stigma Croci, stigma of Crocus sativus L., is a precious traditional Chinese medicine, which is commonly used to activate blood circulation and to dissipate blood stasis. Three plant species, Carthamus tinctorius L., Hemerocallis fulva (L.) L. and Hemerocallis citrina Baroni, could carry the name Stigma Croci in the commercial markets of South East Asia. However, C. sativus is the only one that has proven its effectiveness, while the others could act as adulterants. The authentic identification of C. sativus on the market is difficult. By using molecular genetic method, the spacer domains of 5S-rRNA were cloned from the genomic DNAs that were isolated from C. sativus, C. tinctorius, H. fulva and H. citrina. The cDNAs encoding the spacer domains, about 300 to 500 bp, were sequenced. The nucleotide sequences of these four species showed great diversity, which could serve as markers for authentic identification of Stigma Croci to distinguish from its substitution and counterfeit.

Drugs, Chinese Herbal↗

PubMed2001

A novel eleven-membered-ring triterpene dilactone, pseudolarolide F and A related compound, pseudolarolide E, from Pseudolarix kaempferi.

A novel eleven-membered-ring triterpene dilactone, pseudolarolide F (1), and a related compound, pseudolarolide E (2), were isolated from the seeds of Pseudolarix kaempferi, a plant indigenous to eastern China. Their structures and stereochemistry were established by spectroscopic studies, which included UV, IR, HREIMS, 2D NMR correlation methods (1H-1H COSY, 13C-H COSY, NOESY, HMQC, and HMBC), and single-crystal X-ray analysis.

China↗

PubMed2000

Synthesis of 5-substituted analogues of huperzine A.

Three 5-isosteres of huperzine A (2-4) were first synthesized. The key intermediate 10 was prepared by the reaction of acid 13 with LTA. The compounds 2 and 3 had 50% inhibition by 35 and 47 microM, respectively, which still retained antiacetylcholinesterase activity.

Acetylcholinesterase↗

PubMed2000

Tumor necrosis factor alpha enhances the cytotoxicity induced by nitric oxide in cultured cerebral endothelial cells.

It has been shown that independent sources of nitric oxide (NO) and the inflammatory cytokine tumor necrosis factor alpha (TNFalpha) contribute to the breakdown of the blood-brain barrier (BBB) in the pathogenesis of a number of brain disorders. However, the interaction of NO and TNFalpha has not been elucidated. The present study was designed to determine whether the toxicity induced by NO is altered by TNFalpha in brain capillary endothelial cells (BCECs), and if so, whether it is related to the generation of superoxide. TNFalpha (50-400 U/ml) did not produce toxicity until at a concentration of 800 U/ml. This toxic effect was completely blocked by copper-zinc superoxide dismutase (SOD)/catalase or N(omega)-nitro-L-arginine methyl ester (L-NAME) or oxyhemoglobin (HbO2). Sodium nitroprusside (SNP) reduced with 0.4 mM ascorbate (SNP/Vc) significantly increased Lactate dehydrogenase (LDH) efflux in a concentration-dependent manner. This cytotoxicity of SNP/Vc was also completely inhibited by SOD/catalase or HbO2. When SNP/Vc used in combination with 400 U/ml TNFalpha, a more remarkable LDH efflux was induced than SNP/Vc alone, even as little as 0.01 mM SNP/Vc was toxic, although a dose of 400 U/ml TNFalpha alone had no effect on LDH efflux. In addition, either 0.4 mM SNP/Vc and 800 U/ml TNFalpha alone or 0.4 mM SNP/Vc and 400 U/ml TNFalpha in combination significantly increased malondialdehyde (MDA) content, but nitric oxide synthase (NOS) activity was inhibited only by SNP/Vc and TNF in combination. These results suggest that TNFalpha enhances the toxicity of NO in BCECs and that at least part of this enhancement involves the generation of superoxide.

Animals↗

PubMed2000

Species identification of Radix Astragali (Huangqi) by DNA sequence of its 5S-rRNA spacer domain.

About 300 species and varieties of Astragalus are identified in China, making the identification of the origin of a particular Astragalus species on the consumer market difficult. A molecular genetic approach was developed to identify various species of Astragalus. Although the 5S-rRNA coding sequence is conserved in higher eukaryotes, the spacer domain of the 5S-rRNA gene has great diversity among different species. The 5S-rRNA spacer domain was amplified by polymerase chain reaction (PCR) from the isolated genomic DNA, and the PCR products (approximately 300 bp) covering the 5S-rRNA spacer domain were sequenced. The nucleotide sequences of Astragalus membranaceus, A. membranaceus var. mongholicus, A. lehmannianus, A. hoantchy, and of one closely related species Hedysarum polybotrys (Hongqi), were determined. Diversity in DNA sequence and restriction enzyme mapping among various species was found in their 5S-rRNA spacer domains. This is the first report on the detection of 5S-rRNA spacer region sequence of Astragalus, and the results could be used for genetic identification of Huangqi.

Astragalus propinquus↗

PubMed2000

Phenylpropanoid glycosides from Scrophularia ningpoensis.

Three phenylpropanoid glycosides named ningposides A (3-O-acetyl-2-O-feruloyl-alpha-L-rhamnopyranose), B (4-O-acetyl-2-O-feruloyl-alpha-L-rhamnopyranose) and C (3-O-acetyl-2-O-p-hydroxycinnamoyl-alpha-L-rhamnopyranose) along with the known compounds sibirioside A, cistanoside D, angoroside C, acteoside, decaffeoylacteoside and cistanoside F were obtained from the roots of Scrophularia ningpoensis.

Glucosides↗

PubMed2000

Effect of magnesium tanshinoate B on the production of nitric oxide in endothelial cells.

Nitric oxide (NO) is a potent vasodilator which plays an important role in regulating vascular tones. Danshen, a Chinese herbal medicine has been widely used for the treatment of cardiovascular diseases. The objective of this study was to investigate the effect of magnesium tanshinoate B (MTB), a compound purified from Danshen, on the production of NO in human endothelial cell line (ECV304). After cells were incubated with MTB (1-10 microM) for 1 or 4 h, amounts of NO metabolites released by cells were quantified and cellular NOS activities were determined following the conversion of [3H]arginine to [3H]citrulline. The NOS protein expression was determined by Western immunoblotting analysis. MTB (1-10 microM) stimulated the release of NO and its metabolites from endothelial cells. Following MTB treatment, the cellular NOS activities were significantly enhanced with a concomitant increase in the levels of constitutive NOS (cNOS) protein mass (110-178%). Selective activation of cNOS by MTB may be employed therapeutically in modulating NO production in endothelial cells.

Blotting, Western↗

PubMed2000

Fast repairing of oxidized OH radical adducts of dAMP and dGMP by phenylpropanoid glycosides from Scrophularia ningpoensis Hemsl.

AIM: To investigate the antioxidative activity of the constituents of the roots of Scrophularia ningpoensis (Chinese name: Xuanshen). METHODS: The main compounds from the roots of Scrophularia ningpoensis were isolated and identified by chromatography and FABMS, NMR etc. Using the techniques of pulse radiolysis, the electron transfers from iridoid glycosides (IG) or phenylpropanoid glycosides (PG) to oxidized OH radical adducts of 2'-deoxyadenosine-5'-monophosphate acid (dAMP) or 2'-deoxyguanosine-5'-monophosphate acid (dGMP) were observed. RESULTS: Two IG: harpagoside and harpagide, two PG: angoroside C and acteoside were obtained as the main hydrophilic constituents of the plant. At 0.1 mmol/L concentration, angoroside C and acteoside were able to repair the oxidized OH adducts dAMP and dGMP significantly. However, harpagoside and harpagide had no such effect. The electron transfer rate constants of angoroside C with dAMP and dGMP were 4.2 x 10(8) and 10.3 x 10(8) L.mol-1.s-1; the electron transfer rate constants of acteoside with dAMP and dGMP were 5.3 x 10(8) and 20.2 x 10(8) L.mol-1.s-1. CONCLUSION: PG from Scrophularia ningpoensis have a potent antioxidative activity for reducing of the oxidized OH adducts of dAMP and dGMP.

Antioxidants↗

PubMed1999

Two dichromenes from Evodia lepta.

Two new dichromenes, dichromene C and dichromene D, were isolated from the aerial parts of Evodia lepta. Their structures were determined by spectroscopic analysis.

Benzopyrans↗

PubMed1997

Manuifolins D, E, and F: new isoflavonoids from Maackia tenuifolia.

Chemical examination of roots of Maackia tenuifolia yielded three new isoflavans, manuifolins D, E, and F, along with the known (6aR, 12aR)-pterocarpin and (6aR,12aR)-maackiain. The new compounds were established as (3R)-5'-(1,1-dimethyl-2-propenyl)-4'- O-(3-methyl-2-butenyl)- 7,2'-dihydroxyisoflavan (1), (3R)-6,5'-bis(1,1-dimethyl-2-propenyl)-7,2',4', -trihydroxyisoflavan (2), and (3R)-5'-(1-isopropylethenyl)-8-(3-methyl-2-butenyl)-7,2',4'- trihydroxyisoflavan (3), respectively, by spectroscopic methods.

Fabaceae↗

PubMed1997

[Actions of salvianolic acid A on CCl4-poisoned liver injury and fibrosis in rats].

AIM: To study the actions of salvianolic acid A (SA-A) on liver injury and liver fibrosis. METHODS: The liver fibrotic rat was made by i.p. injection of CCl4. The model rats were divided into 3 groups treated with SA-A, colchicine (Col), and Salvia miltiorrhiza Bunge (SMB), respectively. Six wk later the rat liver pathology was examined, type I and III collagen in the liver were examined by immunohistochemistical method. Also hydroxyproline (Hyd) and malondialdehyde (MDA) in the liver, alanine aminotransferase (AlaAT), aspartate aminotransferase (AspAT), and albumin (Alb) levels in the serum were measured. RESULTS: SA-A inhibited serum AlaAT and AspAT activities, decreased MDA and Hyd contents, alleviated liver fibrogenesis, protected deposition of type I and III collagen in liver matrix. The actions of SA-A on liver fibrosis were similar to those of Col and SMB, action of SA-A decreasing MDA was better than that of Col. CONCLUSION: SA-A has marked effects against liver injury and fibrosis, associated with its anti-lipid peroxidation actions.

Alanine Transaminase↗

PubMed1997

[Synthesis and antiarrhythmic activity of some (erythro)-phenylpropanediolamine compounds].

For the purpose of searching for new drug with high potency and simple chemical structure, the dominant conformation and structural parameters of Guan-Fu base (GFA) molecule were modelled and calculated with a SGI-4D 25G computer. The propanediolamine chain in GFA might be considered to be a pharmacophore responsible for the bioactivity and the configuration of the chain seemed important. Thus, thirteen compounds of (erythro)-p-x-PhCHOHCHOHCH2NHR(x = H, I1-7; X = NO2, II1-6) were prepared. Among them, 10 compounds showed antiarrhythmic effect on aconitine-induced arrhythmia in rats. The ED50(to stop VT) of I2 and ED50(to stop VP) of I3 were shown to be comparable with those of GFA. In the synthesis, no stereoselectivity was found in the Prevost reaction with allylamine analogues (a1-7). After a1-7 were acetylated, the erythro type products(I1-7) were obtained.

Aconitine↗

PubMed1997

[The isolation and identification of four new 2, 2-dimethylchromenes].

Four new 2, 2-dimethylchromenes named leptol B (I), ethylleptol B (II), methylleptol B (III), leptene B (IV), along with a known chromene-methylevodionol (V) have been isolated from the aerial parts of Evodia lepta. Their structures were elucidated by spectroscopic analysis and chemical techniques.

Benzopyrans↗