[Chronic heart failure due to Qi deficiency and blood stasis and intervention mechanism of Compound Renshen Buqi Granules:a proteomics-based study].

Compound Renshen Buqi Granules have been widely used to treat chronic heart failure(CHF) due to Qi deficiency and blood stasis, but the mechanism of action remains unclear. This paper explored the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules based on quantitative proteomics for uncovering the biological basis. SD rats were divided into the normal control(N) group, normal+Compound Renshen Buqi Granules(ND) group, model(M) group, model+Compound Renshen Buqi Granules(D) group, and positive control(Y) group. The rat model of CHF due to Qi deficiency and blood stasis was established by ligation of the left anterior descending(LAD) coronary artery and chronic sleep deprivation. The rats in the ND group and D group were provided with Compound Renshen Buqi Granules, while those in the Y group received valsartan. Six weeks later, the serum was sampled and the data-dependent acquisition(DDA) was employed for the non-targeted quantitative proteomics analysis of the differences in protein expression among groups, followed by the targeted analysis of differentially expressed proteins(DEPs) generated by data-independent acquisition(DIA). Compared with the N group, the rats in the M group pre-sented with decreased body weight, grip strength, and pulse amplitude and increased RGB value on the tongue surface. The pathomorphological examination revealed inflammatory cell infiltration, cell degeneration and necrosis, tissue fibrosis, etc. After the intervention with Compound Renshen Buqi Granules, multiple indicators were reversed. As demonstrated by proteomics results, there were 144 and 111 DEPs found in the M group and ND group in comparison with the N group. Compared with the M group, 107 and 194 DEPs were found in the D group and the Y group, respectively. Compared with the ND group, 119 DEPs were detected in the D group. As illustrated by DIA-based verification, the quantitative results of six proteins in each group were consistent with those by DDA. The syndrome indicators and pathomorphological examination results demonstrated that the protein expression profile of rats with CHF due to Qi deficiency and blood stasis changed obviously. However, Compound Renshen Buqi Granules were able to reverse the differential expression of immune proteins to regulate CHF of Qi deficiency and blood stasis syndrome, which has provided clues for figuring out the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules.

Hepatoprotective Constituents of Total Dibenzocyclooctadiene Lignans from Schisandra chinensis Based on the Spectrum-Effect Relationship.

To scientifically clarify the hepatoprotective constituents of Fructus Schizandrae chinensis, eleven batches samples of total dibenzocyclooctadiene lignans (TDL) from Schisandra chinensis were prepared by using the optimum extraction technique. Characteristic high-performance liquid chromatography (HPLC) chromatograms were obtained through HPLC analysis technology, and the hepatoprotective effects of the eleven batches of TDL were evaluated by MTT assay. Based on the chemical and biological activity results, the spectrum-effect relationship between the characteristic HPLC fingerprints and the hepatoprotective effect of TDL was established using Minitab 16.0 data analysis software. On the basis of the spectrum-effect relationship, thirteen compounds (1-13) were obtained from the TDL by chemical natural product chemical separation and purification technology, and their structures were identified on the basis of the spectral data and the literature. Based on these compounds, thirteen common peaks among the thirty-three chromatographic peaks in the above HPLC fingerprints were identified. Our findings showed that some components, including, schisandrin B (2), schisandrin A (3), and schisandrol B (7) had significant roles in promoting hepatoprotective activity. Preliminary verification of the spectrum-effect relationship of TDL from S. chinensis was carried out, and the results confirmed that the activity of a composite of these three key components in optimal ratios was better than that of any individual compound, which potentially confirmed the reliability of the spectrum-effect relationship and the synergistic effects of traditional Chinese medicine.

Integrated proteomics and metabolomics analysis of tea leaves fermented by Aspergillus niger, Aspergillus tamarii and Aspergillus fumigatus.

Post-fermented Pu-erh tea (PFPT) is a microbially-fermented tea with distinct sensory qualities and multiple health benefits. Aspergillus are the dominant fungi in the fermentation and the main contributors to the characteristics of PFPT, so their underlying functions warrant detailed study. Here, tea leaves were fermented by Aspergillus niger, Aspergillus tamarii and Aspergillus fumigatus, and resulting samples (designated as Asn, Ast and Asf, respectively) were analyzed by proteomic and metabolomic methods. Changes to the composition of flavonoids, glycerophospholipids, organo-oxygen compounds and fatty acids resulting from Aspergillus fermentation were observed. Carbohydrate-active enzymes, e.g., endoglucanases and cellulases, for degradation of cellulose, starch, lignin, pectin, xylan and xyloglucan were identified. Glycoside hydrolase, glycosyltransferases, tannase, laccases, vanillyl-alcohol oxidases and benzoquinone reductase were identified and hypothesized to catalyze hydrolysis, oxidation, polymerization and degradation of phenolic compounds. Together, functions of Aspergillius were demonstrated as production of enzymes to change concentrations and compositions of metabolites in tea leaves.

18ß-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents.

The oleanane-type triterpene 18ß-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay.

A novel franchetine type norditerpenoid isolated from the roots of Aconitum carmichaeli Debx. with potential analgesic activity and less toxicity.

Further investigation on the phytochemistry of the plant Aconitum carmichaeli Debx. led to isolate a new franchetine type C(19)-diterpenoid alkaloid, guiwuline 1. Its structure was established on the basis of the spectroscopic data (1D and 2D NMR, HRESIMS, UV, IR). In mouse hot-plate test and acute toxicity assay, compound 1 exhibited potential analgesic activity (ED(50), 15 mg/kg) and showed little toxicity to mice (LD(50), 500 mg/kg). The results indicate that compound 1 may be used as a lead molecule to develop novel analgesic agents.

[Chemical constituents from rhizome of Daphne papyracea var. crassiuscula].

OBJECTIVE: To study chemical constituents from rhizome of Daphne papyracea var. crassiuscula. METHOD: Ethyl acetate fraction of 75% ethanol extracts from rhizome of D. papyracea var. crassiuscula, and its strucutre was identified by spectral method. RESULT: Nine compounds were separated and identified as daphneticin (1), daphnetin (2), hydrangetin (3), daphnoretin (4), 1-4'-hydroxyphenyl-5-phenyl-2 (E)-en-1-pentanone (5), daphneolon (6), 3beta-O-acetyl-olean-12-en (7), and (+)-usnic acid (8). CONCLUSION: Compounds 1-8 were separated from D. papyracea var. crassiuscula for the first time. Compound 8 was separated from the genus for first time.

Cerebral artery evaluation of dual energy CT angiography with dual source CT.

BACKGROUND: Conventional computed tomography angiography (CTA) is time consuming, user-dependent and has poor image quality in skull base region. This study assessed the feasibility of a new method, dual energy CTA for depicting the cerebral artery. METHODS: Phantom scan was done with head CTA sequences on dual source CT and 64 spiral CT for radiation dose calculation. Dual energy CTA was done with dual source CT on 36 patients who were suspected of having cerebral vascular disease. Three series axial images in 0.75 mm thick, 0.4 mm increment were acquired, which were named with 80 kV, 140 kV and merged images; 80 kV and 140 kV images were transferred into dual energy software, and maximum intensity projection (MIP) image was generated quickly by dual energy bone remove (DEBR group); merged images were transferred into In Space software to acquire MIP image through manual conventional bone remove (CoBR group). Post processing time and reading time were compared. Image qualities of the two groups were compared, mainly focusing on skull base segments of internal carotid artery and bone subtraction. ANOVA and SNK tests were applied for radiation dose comparison. Student's t test and Wilcoxon rank sum test were applied for assessing differences between data for significance. Cohen's kappa was used for interobserver agreement. RESULTS: Radiation dose of phantom scan showed dual energy CTA was between digital bone subtraction and conventional CTA. The post processing time and reading time were much shorter in DEBR than CoBR, and image quality in skull base was much higher in DEBR than CoBR (P < 0.01). There was no significant difference for suprasellar vessels between two groups (P > 0.5). Interobserver agreement for all vessel segments was excellent (kappa = 0.97). CONCLUSIONS: Dual energy CTA is a reliable, new modality for depicting cerebral artery, overcoming the limitation of conventional CTA in the skull base region. It can save much time in post processing and reading than conventional CTA.

Intravenous leiomyomatosis: diagnosis and follow-up with multislice computed tomography.

Intravenous leiomyomatosis is a rare disease, which appears histologically benign but is clinically aggressive. It is characterized by the intraluminal growth of leiomyomas in the intrauterine and systemic veins. Intravenous leiomyomatosis was reported to have originated in the uterus and extended into the right ventricle via the inferior vena cava (IVC). In these circumstances, it is fatal. Multislice compute tomography (MSCT) allows an early and accurate preoperative diagnosis, resulting in a higher rate of surgical resection and improved survival. The authors present 3 cases of intravenous leiomyomatosis with a history of uterine leiomyoma and hysterectomy. The lesions were found to have extended through the IVC into the right cardiac cavities and were confirmed to be intravenous leiomyomatosis by surgery.

An initial qualitative study of dual-energy CT in the knee ligaments.

OBJECTIVE: To study the clinical application of dual-energy CT (DECT) in the knee ligaments. METHODS: Twelve cases (24 knees) were scanned using dual-energy CT for the knee. Two- and three-dimensional images were used for display in all cases by means of multi-planar reformation (MPR) and volume rendering technique (VRT). All images were ranked by two radiologists according to the grade of knee ligament displayed, the definition of edge and attachment points of the knee ligament. RESULTS: The partial ligaments of 24 knees, such as the patellar ligament, fibular collateral ligament, anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) were clearly displayed; the tibial collateral ligament was not satisfactorily displayed. The transversal ligaments, such as lateral patellar retinaculum and medial patellar retinaculum, and the posterior ligament, such as oblique popliteal ligament could not be shown clearly. CONCLUSION: The dual-energy CT is a new and valuable tool to qualitatively display the main ligaments of the knee.

The value of MDCT in diagnosis of splenic artery aneurysms.

OBJECTIVE: To evaluate the clinical value of multiple detector computed tomography (MDCT) in the diagnosis and planning the treatment of splenic aneurysms. METHODS: Eight cases with splenic artery aneurysms (SAA) were retrospectively reviewed. Sixty four-slice spiral CT scans were performed. Intravenous contrast material was injected at 4ml/s, and arterial and venous phase images were obtained. Subsequently, arterial phase images were analyzed and made for CT angiography. The diagnosis was made by using axial and reconstructive images. All of the patients were also performed Doppler color echocardiography. RESULTS: All patients showed splenic artery and splenic artery aneurysms clearly with CT arterial phase images. Among them, six patients had splenic artery aneurysms, one had giant splenic artery aneurysms (GSAA) and one had splenic artery pseudoaneurysms. Ultrasound examination only diagnosed six of them. CONCLUSION: MDCT is a noninvasive and valuable method in diagnosis of splenic artery aneurysms and has high value in determination of treatment plan.

[Metabolites of R, S-1-(2-methoxyphenyl)-4-[3-(naphtha-1-yl-oxy)-2-hydroxypropyl]-piperazin in rat plasma].

AIM: To study the metabolites of R, S-1-(2-methoxypheyl)-4-[3-(naphthal-yl-oxy)-2-hydroxypropyl] -piperazine, (naftopidil, NAF), a novel antihypertensive drug in rat plasma. METHODS: The rat plasma samples were analyzed by LC/MS after oral administration of NAF. According to MS relativity of metabolites and parent compound (NAF) and metabolic rule of compound with similar structure, the structure of potential metabolites were postulated. Phase I metabolites were identified by HPLC/MS and by comparison with authentic standards, phase II conjugates were indirectly identified with beta-D-glucuronidase in presence or absence of glucuronidase selective inhibitor D-saccharric acid beta-1,4-Lactone. RESULTS: Phase I metabolites desmethyl-naftopidil (DMN), (phenyl) hydroxynaftopidil (PHN), (naphthyl) -hydroxy-naftopidil (NHN) were separated and identified in rat plasma by comparison with reference substances, phase II conjugates, NAF and NHN glucuronide conjugates were separated and tentatively identified by hydrolysis with glucuronidase, the aglycones, NAF and NHN, were identified in rat plasma. CONCLUSION: The major metabolic pathway of NAF in rat plasma should be the hydroxylation of the phenyl or nephthyl moiety of NAF and demethylation of NAF. Therefore, (naphthyl) hydroxyl-metabolite and NAF followed by conjugation with beta-glueuronic acid.

[Quantitative determination of ginkgolides by liquid chromatography-electrospray mass spectrometry].

OBJECTIVE: This paper reports a method based on liquid chromatography coupled with electrospray mass spectrometry for the analysis of terpenoids in ginkgo laminae. METHOD: The analysis was performed on ZORBAX RX-C18 (2.1 mm x 150 mm) column with methanol-water(with gradient) as mobile phase at a flow rate of 0.25 mL x min(-1), and column temperature of 25 degrees C. Analyses were carried out in the selected ion monitoring (SIM) mode. RESULT: Ginkgolides (GA, GB and GC) and bilobalide were quantitatively detected by external standardization with linear in the range of 4.04-1.012 x 10(2) ng, with coefficient and relative standard deviations being 0.993 7-0.999 8 and 2.50%-4.73%. LC-ESI-MS shows a greatly increased sensitivity compared with other methods. The detection limit of this method by SIM was 1.47 x 10(-3)-0.320 microg x mL(-1). CONCLUSION: This method is specific, reproducible, rapidly and permits quantitative analyses of ginkgolides and bilobalide in different samples with simple pre-purification steps.

[Study on the chemical constituents of the volatile oil from Lysimachia trientaloides Hemsl].

The volatile oil from Lysimachia trientaloides Hemsl. was obtained by steam distillation. The chemical constituents were separated and identified by gas chromatography-mass spectrometry (GC-MS). The relative contents in the volatile oil were determined by peak area normalization. The yield of oil by steam distillation was 0.11%, and 40 chemical constituents were separated and identified. Terpenic series and their oxo-derivatives are major chemical constituents in the oil. The main compounds were patchouli alcohol(22.54%), L-bornyl acetate(16.17%), gamma-gurjunene(3.27%), delta-guaiene(2.62%), nerolidol(2.02%), linalool(1.99%) and palmitic acid(1.96%).