Acetamides ; pharmacology ; Animals ; Bridged-Ring Compounds ; poisoning ; Disease Models, Animal ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; Troponin I ; blood

OBJECTIVETo explore the inhibitory effect of norcantharidin (NCTD) on the expression of DNA replication initiation protein Cdc6 in cancer cells.

METHODSMTT assay was performed to detect the inhibitory effect on different cancer cell lines, including HeLa, HepG2, Jurkat and Ramos cells. The effect of NCTD on Cdc6 protein level was detected by Western blotting, and BrdU incorporation assay was used to evaluate the DNA replication of the cells.

RESULTSNCTD significantly inhibited the proliferation of the cells and caused degradation of Cdc6 protein to result in the inhibition of the DNA replication of the cells shown by BrdU incorporation assay.

CONCLUSIONNCTD can induce the degradation of Cdc6 in cancer cells to produce an anti-cancer effect.

Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; DNA Replication ; drug effects ; Humans ; Nuclear Proteins ; metabolism

OBJECTIVETo observe the effect of different doses of acetamide on the histopathology in the cerebral cortex of rats with tetramine (TET) poisoning and to provide a basis for the treatment of fluoroacetamide poisoning with acetamide.

METHODSEighty clean Sprague-Dawley rats were randomly divided into five groups: saline control group,dimethylsulfoxide water solution control group,TET poisoning group, acetamide (2.88 g/kg/d) treatment group, and acetamide (5.68 g/kg/d) treatment group, with 16 rats in each group. Rats in the poisoning group and treatment groups were poisoned with TET by intragastric administration after fasting; then, saline was injected intramuscularly into rats of the poisoning group, and different doses of acetamide were injected intramuscularly into rats of treatment groups; the course of treatment was 5 d. At 3 h, 12 h, 48 h, and 7 d after treatment, the cerebral cortex was harvested from rats in each group, and the histopathological changes in the cerebral cortex were evaluated under light and electron microscopes.

RESULTSThe light microscopy showed that the TET poisoning group had hypoxia changes in the cerebral cortex, which worsened over time; the treatment groups had reduced hypoxia changes, and the acetamide (2.88 g/kg/d) treatment group had more reduction than the acetamide (5.68 g/kg/d) treatment group. The electron microscopy showed that the apoptosis of neuronal cells were the main pathological changes in the TET poisoning group; the treatment groups had reduced apoptotic changes, and the acetamide (2.88 g/kg/d) treatment group had more reduction than the acetamide (5.68 g/kg/d) treatment group.

CONCLUSIONNo pathological changes associated with the synergistic toxic effect of acetamide and TET are found in the cerebral cortex. Acetamide (2.88 g/kg/d) could reduce central nervous lesions, but the efficacy is not improved after increasing the dose. For patients who cannot be identified with TET or fluoroacetamide poisoning, acetamide could be considered for treatment.

Acetamides ; pharmacology ; Animals ; Bridged-Ring Compounds ; toxicity ; Cerebral Cortex ; drug effects ; pathology ; Disease Models, Animal ; Male ; Rats ; Rats, Sprague-Dawley

In order to find the endogenous potential biomarkers of in vitro hepatic injury caused by NCTD-Na and elucidate the mechanism of hepatic injury of NCTD-Na,ultra-high performance liquid chromatography coupled quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used for lipidomics detection.Multivariate statistical analysis was used to study the endogenous lipid metabolic changes of human normal liver cells LO2 injury after the treatment with sodium norcantharidate(NCTD-Na).The results showed that the half maximal inhibitory concentration(IC50) of NCTD-Na was 0.034 mmol·L-1.A total of 280 differential metabolites were found between the control group and the low-dose group,with VIP > 2.0 and P<0.05.At the same time,a total of 273 differential metabolites were found between the control group and the high-dose group,with VIP > 2.0 and P<0.05.Cell metabolite profiles showed clear separation among control group,the low-dose group and the high-dose group,and 111 differential metabolites were found,with VIP > 2.0,P<0.05,RSD<30% and in a dose-dependent manner.It was found that most of the above differential metabolites were lipid metabolites after the analysis of simple preparnation methods and database search.A total of 32 potential biomarkers were identified,including 3 phosphatidylcholine(PC),5 lysophosphatidylcholine(Lyso PC),3 ceramide(Cer),1 sphingomyelin(SM),1 phosphatidylethanolamine(PE),10 lysophosphatidylethanolamine(LysoPE),4 diacylglycerol(DG),1 Phosphatidic acid(PA),1 lysophosphatidic acid(Lyso PA),1 phosphatidyl glycerol(PG),1 fatty acid hydroxy fatty acid(FAHFA) and 1 phosphatidylserine(PS).The changes of PCs,Cers,SM,PE and DGs were closely related liver protection,DNA methylation and self-repair in hepatocytes,apoptosis,methylation and detoxification of carcinogens,as well as lipid peroxides production process.Also,they had impact on the proliferation of hepatocytes,differentiation and gene transcription disorders.Cells stimulated by NCTD-Na could promote the production of PA as well as the synthesis and catabolism of FAHFA in a variety of ways.The levels of Lyso PCs,LysoPEs and Lyso PA were correlated with PCs,PE and PA;PE and PS might have valgus during apoptosis,triggering phagocytosis.
Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Cells, Cultured ; Hepatocytes ; drug effects ; metabolism ; Humans ; Lipid Metabolism ; Lipids ; analysis ; Tandem Mass Spectrometry

AIMTo design and synthesize a series of new taxoids with a 5-O-sidechain, and to test the multi-drug resistant reversal activity of these compound on KB/V200 cells which is 180 times more resistant to vincristine.

METHODSUsing Sinenxan A as a common synthetic starting material, three different types of 5-O-sidechain molecules were synthesized through different route. For type I compounds, 14-acetoxy of Sinenxan A was selectively removed by hydrolysis, xanthation and reduction with tributyltin; A C-10-oxo group was introduced by PCC oxidation; 5-O-acetyl group was selectively removed by potassium tert-butoxide and finally the side chain was introduced by acylating with the corresponding acid. For type II compounds, 5-O-sidechain was introduced to the 5-deacetyl Sinenxan A which was obtained by selective hydrolysis with tBuOK. For type III compounds, 9-acetoxy group was introduced, then 5-OH was left free by thorough hydrolysis and reacetylation. Acylation at 5-position, the final product was obtained. Structure of the compounds have been confirmed by FABMS and 2DNMR. The activity of the compounds in vitro was tested on KB/V200 resistant cell line using MTT method.

RESULTSNine compounds showed resistant reversal activity and enhancing the cytotoxicity of vicristine against KB/V200 cells. Compounds I2, I3, I4 restored the sensitivity of KB/V200 towards vicristine to a level of IC50 at 1 x 10(-8) mol.L-1 which is better than the positive control Verapamil.

CONCLUSIONThe drug resistant reversal activity of taxane derivatives can be affected by substitution at different positions and the length of side chains of Sinenxan A. It is worthy to be further studied.

Antineoplastic Agents ; pharmacology ; Bridged-Ring Compounds ; chemical synthesis ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Drug Synergism ; Humans ; KB Cells ; drug effects ; Taxoids ; chemical synthesis ; pharmacology ; Vincristine ; pharmacology

OBJECTIVETo study the effects of blood enriching on mouse model of blood deficiency syndrome of Paeoniae Radix Alba and Paeoniae Radix Rubra, paeoniflorin and albiflorin.

METHODBuilding the mouse model of blood deficiency syndrome induced by compound method of bleeding, starved feeding and exhausting of swimming, extract from Paeoniae Radix Alba and Paeoniae Radix Rubra were given during modeling. The amount of RBC, HGB were detected after the treatment. Based on the amount results of RBC, HGB and the paeoniflorin content, albiflorin content in Paeoniae Radix Alba and Paeoniae Radix Rubra, the same model and the same method were used to comparatively study the effect of blood enriching of paeoniflorin and albiflorin.

RESULTAt the 7th day, the amount of RBC and HGB in model mice was significantly increased (P <0. 01) by 2 g kg-1 Paeoniae Radix Alba and 2 g kg-1 Paeoniae Radix Rubra. At the 14th day, the amount of RBC and HGB in model mice was significantly increased (P <0. 01) by 2 g kg-1 Paeoniae Radix Alba. The amount of RBC and HGB in mice treated with Paeoniae Radix Rubra had an increasing trend compared with the same dose of Paeoniae Radix Rubra, but the difference was not significant. In another experiment with the same model, the amount of RBC and HGB in model mice was significantly increased (P<0.01) by 120 mg kg-1 paeoflorin and 120 mg kg-1 albiflorin at the 7th day, meanwhile, 60 mg kg-1 and 30 mg kg-1 albiflorin also increased the amount of RBC and HGB. At the 14th day, 120 mg kg-1 paeoflorin and all doses of albiflorin increased the amount of RBC and HGB. Comepared with that of the same dose of paeoniflorin, the amount of RBC in mice was significantly increased (P <0. 05) by 30 mg kg-1 albiflorin and 120 mg kg-1 albiflorin; the amount of HGB was significantly increased (P <0. 05) by 30 mg kg -1 albiflorin.

CONCLUSIONPaeoniae Radix Alba has a better effect of blood enriching than Paeoniae Radix Rubra. Albiflorin is more effective in blood enriching than paeoniflorin. Combining these, it infers that albiflorin involves in the better blood enriching effect of Paeoniae Radix Alba.

Animals ; Benzoates ; pharmacology ; Bridged-Ring Compounds ; pharmacology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Erythrocytes ; drug effects ; Glucosides ; pharmacology ; Hemoglobins ; drug effects ; Male ; Mice ; Monoterpenes ; Paeonia ; chemistry

OBJECTIVETo study the effects of four trace elements Mn, Fe, Zn and Cu on growth of the 2nd- and the 3rd-years Paeonia lactiflora.

METHODThe experiment was designed as randomized blocks. The data of physiological parameters such as fresh weight of root, numbers of bud and root division, length and diameter of the root and the contents of paeoniflorin in root were measured after fertilized with the four trace elements. Also the contents of the four trace elements in soil and roots, stem and leaves of P. lactiflora were detected by atomic absorption spectrometry.

RESULT AND CONCLUSIONThe growth of the P. lactiflora was improved and the content of paeoniflorin was increased by proper level of Mn, Fe, Zn and Cu, but depressed by the higher level. Only Zn can be accumulated in the roots of P. lactiflora.

Benzoates ; metabolism ; Bridged-Ring Compounds ; metabolism ; Copper ; pharmacology ; Glucosides ; metabolism ; Iron ; pharmacology ; Manganese ; pharmacology ; Monoterpenes ; Paeonia ; drug effects ; growth & development ; metabolism ; Spectrophotometry, Atomic ; Zinc ; pharmacology

OBJECTIVETo study the blood enriching effects of Paeoniae Radix Rubra and Paeoniae Radix Alba, paeoniflorin and albiflorin on mouse model of blood deficiency caused by γ-ray radiation.

METHODBuild mouse model of blood deficiency induced by γ-ray radiation. Paeoniae Radix Rubra and Paeoniae Radix Alba were given during modeling. The amount of WBC was detected af- ter the treatment. Based on the result of WBC and paeoniflorin content, albiflorin content in Paeoniae Radix Rubra and Paeoniae Radix Alba, the same model and the same method were used to comparatively study the effect of blood enriching of paeoniflorin and albiflorin.

RESULTOn the 7th day, the amount of WBC in model mice treated with 2 g x kg(-1) Paeoniae Radix Alba and 2 g x kg(-1) Paeoniae Radix Rubra significantly increased compared with that of model group (P < 0.05). In another experiment with the same model, the amount of WBC in model mice treated with 120 mg x kg(-1) paeoflorin and 120 mg x kg(-1) albiflorin significantly increased (P < 0.05) compared with that of model group on the 7th day. On the 10th day, the amount of WBC in rats treated with 120 mg x kg(-1) paeoflorin increased significantly (P < 0.05) compared with that of model group. Compared with the same dose of paeoniflorin, the amount of WBC in mice treated with albiflorin had no significant difference.

CONCLUSIONAll Paeoniae Radix Alba, Paeoniae Radix Rubra, paeoniflorin and al- biflorin can raise the amount of WBC and have the effect of enriching blood induced by radiation, while paeoniflorin and albiflorin have a similar result in this model. The result indicated that both paeoniflorin and albiflorin are effective constituents in Paeoniae Radix Alba, and paeoniflorin work as the common effective constituent in both Paeoniae Radix Rubra and Paeoniae Radix Alba.

Animals ; Bridged-Ring Compounds ; pharmacology ; Gamma Rays ; adverse effects ; Glucosides ; pharmacology ; Leukocyte Count ; Leukocytes ; cytology ; drug effects ; radiation effects ; Male ; Mice ; Monoterpenes ; pharmacology ; Rats

Taxus canadensis distributed mainly in North America, such as northern Minnesota, Newfoundland, south to Wisconsin and Pennsylvania. Its composition has been shown to be very different from other species, and in recent years, some new skeletons also have been found in Canada yew. Through analysis of the taxanes content on various Taxus plants containing taxanes, the results showed a higher content of taxol in T. canadensis. Based on the current research on T. canadensis (from the research results of the author in recent years, as well as from studies of scholars in the field), the paper outlined the research progress in recent years on the chemical constituents of taxane of T. canadensis and the spectral characteristics of various types of compounds. Besides, this paper analyzed the present research about solutions for the taxol drug source crisis.
Animals ; Bridged-Ring Compounds ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Plant Extracts ; chemical synthesis ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; Taxoids ; chemical synthesis ; chemistry ; pharmacology ; Taxus ; chemistry

Animals ; Apoptosis ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Cell Line ; Hypoxia ; MicroRNAs/genetics* ; Myocardial Reperfusion Injury/drug therapy* ; Myocytes, Cardiac ; Oxidative Stress ; Rats ; Reperfusion Injury ; Tetrahydronaphthalenes/pharmacology*