Three New Isomeric Indole Alkaloids from Nauclea officinalis.

Three new isomeric monoterpene indole alkaloids, naucleofficines I-III (1-3, resp.) were isolated from the stems (with bark) of Nauclea officinalis. Their structures were elucidated on the basis of spectroscopic methods and single-crystal diffraction analyses. The cytotoxic activities of 1-3 against human colon cancer, human gastric cancer, and human hepatoma cells were also investigated.

Oldhamianoside II, a new triterpenoid saponin, prevents tumor growth via inducing cell apoptosis and inhibiting angiogenesis.

Oldhamianoside II is a new triterpenoid saponin that was isolated from the roots of Gypsophila oldhamiana. The present study aims to investigate the potential inhibitory activity of oldhamianoside II on tumor growth using an S180 tumor implantation mouse model. Oldhamianoside II at doses of 5.0 and 10.0 mg/kg was given with intraperitoneal injection for 10 days following subcutaneous inoculation of S180 tumor cells in anterior flank of mice. The tumor growth, the cell apoptosis, the microvessel density (MVD) in S180 tumors, the tumor cell viability, the tubular formation in vitro, and migration of tumor cells were examined. The expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and cyclooxygenase-2 (COX-2) was determined to analyze the associated mechanisms. The results showed that oldhamianoside II potently inhibited tumor cell viability in vitro. In addition, oldhamianoside II delayed tumor growth in anterior flank, induced S180 cell apoptosis, and reduced the MVD. Oldhamianoside II was also demonstrated to decrease the number of tubular structure and vessel formation in HUVEC cultures and chick embryo chorioallantoic membrane (CAM) model, respectively. Further study indicated that oldhamianoside II reduced the expression of VEGF, bFGF, and COX-2 in tumor sections. Moreover, oldhamianoside II inhibited the activity of migration and penetration to Matrigel of SGC7901 tumor cells in scratch wound and transwell chamber. In conclusion, our work defines oldhamianoside II, a new triterpenoid saponin, as a novel compound that can effectively inhibit S180 tumor growth, induce tumor cell apoptosis, prevent tumor angiogenesis, and inhibit cancer cell migration, suggesting that oldhamianoside II is a potential drug candidate for the treatment of cancer and for the prevention of metastasis.

First report of Klebsiella oxytoca strain coproducing KPC-2 and IMP-8 carbapenemases.

The study shows for the first time the presence of the Klebsiella oxytoca strain fp10 coproducing plasmid-mediated KPC-2 and IMP-8 carbapenemases. The strain was obtained from the fecal sample of an inpatient and showed high-level resistance to imipenem and ertapenem (MICs > 32 µg/ml). Conjugation experiments demonstrated the transferability of the carbapenem-resistant determinants. The results of plasmid analysis and Southern hybridization revealed that the bla(KPC-2) gene was located on transferable plasmid pFP10-1 (∼54 kb), whereas the bla(IMP-8) gene was on transferable plasmid pFP10-2 (∼180 kb). Analysis of the genetic environment of these two genes has demonstrated that ISKpn6 and ISKpn8 are involved in the spread of the bla(KPC-2) gene, while the transposable elements IS26, intI1, and tniC might contribute to the dissemination of the bla(IMP-8) gene. The chimera of several transposon-associated elements indicated a novel genetic environment of IMP-type metallo-ß-lactamase gene in Enterobacteriaceae from China.

High prevalence of CTX-M ß-lactamases in faecal Escherichia coli strains from healthy humans in Fuzhou, China.

BACKGROUND: The community could be a reservoir of antibiotic resistance genes. The aim of this study was to investigate the prevalence and genetic environments of bla(CTX-M) among faecal Escherichia coli obtained from healthy persons in a region of China. METHODS: Bacteria in stool specimens were screened for extended-spectrum ß-lactamase (ESBL) production on 2 MacConkey agars, one with cefotaxime and one with ceftazidime. bla(CTX-M) and their genetic environments, as well as phylogenetic analysis and detection of the O25b-ST131 clone of E. coli, were characterized by polymerase chain reaction and sequencing. Pulsed field gel electrophoresis and conjugation assays were performed by standard procedures. RESULTS: A surprisingly high number (50.5%, 55/109) of faecal samples showed the presence of ESBL-producing E. coli. bla(CTX-M) genes were detected in all of these strains. The CTX-M-9 group (41/55, 74.5%) was found most frequently, followed by the CTX-M-1 group (16/55, 29.1%). CTX-M-14 (n = 39) was the predominant CTX-M enzyme in this study. However, the genes for the CTX-M-2 and CTX-M-8 groups were not observed. ISEcp1 was detected in 90.9% of the strains, while IS26 was observed upstream from bla(CTX-M) in only 1 strain. Phylogenetic groups A and D were found to predominate in commensal E. coli. High clonal diversity was observed and most bla(CTX-M) genes were transferable. The O25b-ST131 clone was found in 4 strains. CONCLUSIONS: This study reveals the wide dissemination of CTX-M ESBL-producing E. coli in the gut flora of healthy individuals in China.

Phylogenetic groups and pathogenicity island markers in fecal Escherichia coli isolates from asymptomatic humans in China.

The study of phylogenetic groups and pathogenicity island (PAI) markers in commensal Escherichia coli strains from asymptomatic Chinese people showed that group A strains are the most common and that nearly half of all fecal strains which were randomly selected harbor PAIs.

Intravenous colistin sulfate: a rarely used form of polymyxin E for the treatment of severe multidrug-resistant Gram-negative bacterial infections.

In recent reports polymyxins have been considered an effective and safe treatment option for the management of multidrug-resistant (MDR) Gram-negative bacterial infections. Here we report our clinical experience with the use of intravenous colistin sulfate in critically ill patients hospitalized from January 2006 to October 2008, as a last treatment resort in China, and assess its effectiveness and adverse effects. Fifteen patients who suffered from severe infections caused by MDR or pandrug-resistant (PDR) Gram-negative bacteria (13 isolates of Acinetobacter baumannii, 4 isolates of Pseudomonas aeruginosa and 2 isolates of Klebsiella pneumoniae), unresponsive to the initial empirical regimens, were treated with colistin sulfate (daily dose of 1.28 +/- 0.25 million IU and duration of 22.3 +/- 6.2 days), based on sensitivity results. The treatment resulted in a good clinical response in 73.3%, microbiological clearance in 60% and mortality in 20%. Possible nephrotoxicity occurred in 1 patient and no patients developed neurotoxicity. In conclusion, intravenous colistin sulfate is a safe and viable alternative for the treatment of severe infections due to sensitive MDR Gram-negative bacteria.

A new indole alkaloid with anti-inflammatory from the branches of Nauclea officinalis.

A new indole alkaloid, 17-oxo-19-(Z)-naucline, and six known alkaloids 2-7 were isolated from the branches of Nauclea officinalis. The structure of the new compound 1 was characterised mainly by analysing its physical data including IR, 1 D, 2 D NMR, and HR-ESI-MS. Other compounds were identified by comparisons their data with those reported in the literature. Compound1, 4, 5, 6, 7 showed in vitro anti-inflammatory activity decrease the LPS-stimulated production of nitric oxide in RAW264.7 cell, while all compounds exhibited weak cytotoxicity against human tumour cell lines (LOVO, A549 and HepG2).

[Surveillance of antimicrobial resistance among nosocomial gram-negative pathogens from 15 teaching hospitals in China in 2005].

OBJECTIVE: To investigate the antimicrobial resistance among the nosocomial gram-negative pathogens from 15 teaching hospitals located in different areas in China in 2005. METHODS: A total of 1927 non-repetitive nosocomial gram-negative pathogens were collected from 15 teaching hospitals in different areas in China and sent to the central lab for reidentification and susceptibility testing. The levels of minimal inhibitory concentration (MIC) of 18 antimicrobial agents were determined by agar dilution method. WHONET 5.4 software was used to analyze the data. RESULTS: The strains of Escherichia coli, Klebsiella pneumoniae, and Proteous mirabilis isolates that did not produce extended spectrum beta lactamases (ESBLs) showed high sensitivity to beta-lactams. The antibiotics with a susceptibility rates over 80% against the strains of Entorobacter cloacae, Enterobacter aerogene, Citrobacter spp, Serratia spp, and Proteous vulgaris producing AmpC enzyme included meropenem, imipenem, and piperacillin-tazobactam, and these 3 drugs showed a susceptibility rate of more than 80% against the ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Other antimicrobial agents showing a relatively high activity against Enterobacter spp, Citrobacter spp, Serratia spp and Proteous vulgaris included cefepime (67.3% - 100%), amikacin (67.3% - 95.2%), ceftazidime (52.9% - 100%) and cefoperazone-sulbactam (51.9% - 100%). The susceptibility rate of fluoroquinolones was 34.8% - 36.1% against non-ESBL-producing Escherichia coli and was 13.4% - 17.1% against ESBL-producing isolates. The most active agent against Pseudomonas aeruginosa was polymyxin B (95.6%). The agents with the activity rates of 70% - 80% included meropenem, imipenem, amikacin, and piperacillin-tazobactam. The antibiotic with a high susceptible rate against Acinetobacter baumannii was polymyxin B (98.3%), followed by imipenem (80.8%), meropenem (76.2%), and minocycline (67.4%). The susceptible rates of other agents were all below 60%. The agents with relatively high activity against Stenotrophomonas maltophilia included minocycline (85%), levofloxacin (82.5%), and trimethoprim-sulfamethoxazole (77.5%). The agents with a relatively high activity against Burkholderia cepacia included minocycline (77.2%) and meropenem (61.4%). CONCLUSION: Carbapenem, piperacillin-tazobactam, amikacin and cefepime remained relatively high activity against nosocomial Enterobacteriaceae, Non-fermenting pathogens have lower susceptibility to the antimicrobial agents than before.

[Molecular epidemiological study of colistin-only-sensitive strains of multi-drug resistant Acinetobacter baumannii].

OBJECTIVE: To genetically analyze the epidemiology of the colistin-only-sensitive (COS) Acinetobacter baumannii (COS-AB) so as to provide experimental data for controlling COS-AB infection. METHODS: The drug resistance to 14 antibiotics of 136 COS-AB isolates collected in Ruijin Hospital from June 2004 to May 2005 were analyzed. 66 A. baumannii isolates were collected from May to December 2004, of which 33 strains were COS-AB and the other 33 non-COS-AB. Random amplified polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) were applied to analyze the homology of these strains. RESULTS: RAPD analysis (with the primers ERIC2 and 272) showed all COS-AB strains as identical, while PFGE analysis showed that these COS-AB were of two closely related genotypes distinctly different from that of the non-COS-AB. The COS-AB strains obtained from the Burns Ward were PFGE B type causing inter-ward outbreak of single clone. And the COS-AB strains obtained from another wards were PFGE BA type causing inter-departmental outbreak, mainly among the departments of surgical system. CONCLUSION: The cross-infection of COS-AB is severe. Strict disinfection and sterilization should be implemented. The epidemiology of COS-AB in environment and patients should be closely monitored. PFGE analysis is a more accurate method in typing A. baumannii.

Two new triterpenoids from Gypsophila oldhamiana.

Two new triterpenoids (1-2) were isolated and elucidated from the roots of Gypsophila oldhamiana, together with four known triterpenoids (3-6). Their structures were identified to be 3ß-hydroxyolean-13(18)-ene-23, 28-dioic acid (1), 3ß, 12α-dihydroxy-23-carboxyolean-28, 13ß-olide (2), 3ß, 16α-dihydroxy-23-oxoolean-13(18)-en-28-oic acid (3), gypsogenin (4), quillaic acid (5) and gypsogenic acid (6) by spectral methods. All compounds were tested for their cytotoxicities against human tumour cell lines (lung cancer H460 and gastric cancer SGC-7901) and for their antiangiogenic effects using a zebra fish model. All compounds showed interesting antiangiogenic activities and the significant cytotoxicities against H460.

[Isolation and structure identification of the chemical constituents from Gypsophila oldhamiana].

AIM: To study the constituents of the root of Gypsophila oldhamiana Miq. METHODS: Silica gel column chromatographic technique was used for the isolation and purification of compounds. The structures were elucidated on the basis of spectral data and chemical evidences. RESULTS: Five compounds were obtained and identified as the beta-D-glucoside of alpha-spinasterol (I), tetracosyl caffeate (II), sucrose (III), beta-sitosterol (IV) and daucosterol (V). CONCLUSION: Compound II is a new compound. Compound I was isolated from this plant for the first time.

Two new triterpenoids from Nauclea officinalis.

Two new triterpenoids and three 27-nor-triterpenoids were isolated from the stems (with bark) of Nauclea officinalis. Their structures were identified to be 2ß,3ß,19α,23-tetrahydroxy-urs-12-en-28-oic acid (1), 2ß,3ß,19α,23-tetrahydroxy-urs-12-en-28-O-[ß-D-glucopyranosyl (1-2)-ß-D-glucopyranosyl] ester (2), pyrocincholic acid 3ß-O-α-L-rhamnopyranoside (3), pyrocincholic acid 3ß-O-α-L-rhamnopyranosy 1-28-O-ß-D-glucopyranosyl ester (4), pyrocincholic acid 3ß-O-α-L-rhamnopyranosy1-28-O-ß-D-glucopyranosyl-(1-6)-ß-D-glucopyranosyl ester (5) by spectroscopic methods including 1D, 2D NMR and HR-MS analyses. The cytotoxic activity of 1-5 against lung cancer A-549 cells was also investigated.

Bioactive ent-clerodane diterpenoids from Scutellaria barbata.

Four new ENT-clerodane diterpenoids were isolated from the whole plant of Scutellaria barbata D. Don. (Labiatae). Their structures were elucidated by chemical methods and spectral analyses. in vitro, the four new compounds showed significant cytotoxic activities against three human cancer lines (HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells), and gave IC50 values in the range 3.1-7.2 microM.