Bioaccessibility analysis of active components in Salvia miltiorrhiza / 药学学报

In this study, a method for simultaneous quantitative analysis of 6 salvianolic acids and 4 tanshinones in extracts of Salviae Miltiorrhizae Radix et Rhizoma was established by ultra-high performance liquid chromatography (UHPLC). The semi-biomimetic method was applied to simulate digestion process in vitro, to explore the digestion and transport characters of oral administration through the gastrointestinal tract, and to explain the content ratio changes and bioaccessibility of active ingredients in Salviae Miltiorrhizae Radix et Rhizoma. The results showed that the 10 index components have a good linear relationship in the corresponding concentration range, and the average recovery rate was 91.35% to 105.65%. After simulated digestion in vitro, types of chemical composition in simulated gastric fluid and simulated intestinal fluid digested extracts of Salviae Miltiorrhizae Radix et Rhizoma did not change significantly. While the content ratio of salvianolic acid B and rosmarinic acid decreased, and the content ratio of protocatechuic aldehyde and danshensu increased. In the simulated gastric fluid digestion extract of Salviae Miltiorrhizae Radix et Rhizoma, the order of bioaccessibility was: danshensu (50.19%) > salvianolic acid B (33.44%) > lithospermic acid (27.34%) > salvianolic acid A (21.71%) > rosmarinic acid (12.31%). In the simulated intestinal fluid digestion extract of Salviae Miltiorrhizae Radix et Rhizoma, the order of bioaccessibility was: 15,16-dihydrotanshinone Ⅰ (5.45%) > tanshinone Ⅰ (3.67%) > cryptotanshinone (3.29%) > tanshinone ⅡA (3.01%) > salvianolic acid A (2.39%) > lithospermic acid (1.57%) > salvianolic acid B (1.02%) > danshensu (0.41%) > rosmarinic acid (0.34%). In conclusion, the UHPLC method established in this study can be applied for accurately and sensitively detecting the contents of 6 salvianolic acids and 4 tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. The results of semi-biomimetic extraction showed that not all components were extracted with simulated gastric fluid and simulated intestinal fluid, especially rosmarinic acid and salvianolic acid B. Therefore, in the quality study of Salviae Miltiorrhizae Radix et Rhizoma and its extract, bioavailability should be considered at the same time when select quality markers and determine their content limits.

Identification and application of biomarkers in life cycle of drugs / 药学学报

Biomarkers are defined as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Biomarkers can help the decision-making process for new drug research and development, provide guidance for the early clinical development of candidate drugs and reduce the risk of failure. Therefore, as a key factor in the development of new drugs, the discovery and research on biomarkers has increased the interest of the pharmaceutical industry and regulatory agencies. Guidelines on the development and use of biomarkers have been issued by drug regulatory agencies including the EMA, FDA and ICH. Biomarkers are encouraged to be used to facilitate drug development by these relevant regulatory agencies, and also to be used to monitor the safety and efficacy of drugs in post-marketing drug surveillance. The application of biomarkers is encouraged at different stages of a drug's life cycle, including at the stage of basic science research and target identification, prototype design or discovery, preclinical development, clinical development, FDA filling/approval and launch, as well as post-marketing was reviewed. The identification, development, and application of biomarkers in pharmaceutical research is discussed.

Discovery of quality markers of traditional Chinese medicine compounds and visualization technology of content-effect colour atla / 药学学报

The chemical composition of traditional Chinese medicine (TCM) compounds is complex, the treatment is broad, and the quality control indexes cannot accurately reflect the functional properties. According to the above problems, the authors take the research process of quality markers of Qizhiweitong granules as an example to innovate the research ideas and technical methods, and constructed five progressive steps of TCM compounds quality control and evaluation model: "based on function, to figure out the attending", "components and pharmacodynamics correlation, multiple components with multiple effects", "to analyze the components, and systematically integrate them", "spectrum and effect correlation, from a spectrum to see the efficiency", and "from the content-effect colour atla to see the quality". Based on the multiple effects of components, multiple components of multi-effect pharmacological efficacy evaluation system were established. All-time isobaric multiwavelength fusion fingerprint technology was improved and developed. "Spectrum-effect colour atla" software was research and developed for the first time, to realize the "visualization" of TCM efficacy. The aim of this work is to provide an exploratory solution for the integrated quality control of TCM compounds.

Revalidating Pfirrmann's Magnetic Resonance Image-Based Grading of Lumbar Nerve Root Compromise by Calculating Reliability among Orthopaedic Residents

BACKGROUND: Intervertebral disc herniations lead to subsequent compromise of the nerve root. The root can either have a mere contact with the disc material or be pushed aside or compressed. This was earlier graded by Pfirrmann and colleagues. We intend to revalidate this grading system by performing a reliability analysis among orthopaedic residents. METHODS: Fifty axial cut magnetic resonance (MR) images of the affected lumbar disc level that belonged to different patients (age, 37.8 ± 10.4 years; 33 males and 17 females) were chosen and given to five orthopaedic residents for grading according to the Pfirrmann's MR image-based grading of lumbar nerve root compromise. Responses were received in the form of categorical variables and reliability was assessed. RESULTS: On doing percentage statistics, we found that 14 images had 100% agreement, 22 had 80% agreement and 14 had 60% agreement. We inferred an overall agreement of 80% ± 15.1%. In addition, interrater reliability was determined by calculating the Fleiss' kappa, which was found to be 0.521, signifying moderate agreement. Intrarater reliability was determined by calculating Cohen's kappa, which was found to be 0.696, signifying substantial agreement. CONCLUSIONS: Our residents took only a short time to learn and reproduce this grading system as ratings that proved to be moderately reliable. Even though the value of kappa was slightly lower, reliability was similar to that of the original authors. We think that this grading system can be adopted in day-to-day practice by framing appropriate rules to interpret MR images where the nerve roots are not visible.

Study on the risks and its influencing factors of patients with psychotic disorders in communities / 中华行为医学与脑科学杂志

Objective To explore the risks and its influencing factors of patients with psychotic disorders in communities.Methods A total of 457 patients with psychotic disorders in communities were investigated by use of the multistage stratified cluster random sampling method.Results Totally 257 patients with psychotic disorders in communities were with risks,which accounted for 56.2％.Among them,200 patients (43.8％) were with level-0 risk,113 patients (24.7％) were level-1 risk,85 patients (18.6％) were level-2 risk,43 patients (9.4％) were level-3 risk,11 patients (2.4％) were level-4 risk,while 5 patients (1.1％) were level-5 risk.There were significant differences in risks among patients with different gender,family income,duration,type of disease,medication and the history of violent behavior.Logistic regression analysis showed that low family income (OR=0.515,95％ CI=0.386-0.689,P＜0.01),long course of disease (OR=1.378,95％CI=1.179-1.609,P＜0.01),patients with schizophrenia (OR=6.285,95％CI=2.456-16.086,P＜ 0.01) and patients with a history of violence history (OR=28.988,95％CI=10.692-78.592,P＜0.01) were the risk factors of the influencing of patients with psychotic disorders in communities.Conclusions Low family income,long course of disease,patients with schizophrenia and a history of violence history are the influencing factors of patients with psychotic disorders in communities,and the management of follow-up and the strength of supervision among these patients should be reinforced.

Assessment of Anteroposterior Subpedicular Approach and Oblique Scotty Dog Subpedicular Approach for Selective Nerve Root Block

BACKGROUND: The technique used to administer a selective nerve root block (SNRB) varies depending on individual expertise. Both the anteroposterior (AP) subpedicular approach and oblique Scotty dog subpedicular approach are widely practiced. However, the literature does not provide a clear consensus regarding which approach is more suitable. Hence, we decided to analyse the procedural parameters and clinical outcomes following SNRBs using these two approaches. METHODS: Patients diagnosed with a single lumbar herniated intervertebral disc (HIVD) refractory to conservative management but not willing for immediate surgery were selected for a prospective nonrandomized comparative study. An SNRB was administered as a therapeutic alternative using the AP subpedicular approach in one group (n = 25; mean age, 45 ± 5.4 years) and the oblique Scotty dog subpedicular approach in the other group (n = 22; mean age, 43.8 ± 4.7 years). Results were compared in terms of the duration of the procedure, the number of C-arm exposures, accuracy, pain relief, functional outcome and the duration of relief. RESULTS: Our results suggest that the oblique Scotty dog subpedicular approach took a significantly longer duration (p = 0.02) and a greater number of C-arm exposures (p = 0.001). But, its accuracy of needle placement was 95.5% compared to only 72% using the AP subpedicular approach (p = 0.03). There was no significant difference in terms of clinical outcomes between these approaches. CONCLUSIONS: The AP subpedicular approach was simple and facile, but the oblique Scotty dog subpedicular approach was more accurate. However, a brief window period of pain relief was achieved irrespective of the approaching technique used.

Effect of processed Polygonum multiflorum on mRNA expression level of five subtypes of CYP450 enzymes in rat liver / 中国中药杂志

To observe the effect of processed Polygonum multiflorum on mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. SD rats were randomly divided into the normal control group, processed P. multiflorum high dose and low dose groups (5.40 g•kg⁻¹ and 1.08 g•kg⁻¹). The rats in administration groups were continuously given with processed P. mutiflorum for 7 days by ig administration, and the rats in normal control group were given with the same volume of distilled water. After successive administration of 7 days, the serum biochemical indications were detected, and Real-time quantitative PCR technology was used to detect the mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. Experimental results showed that AST was decreased significantly in both low and high dose groups. ALT was significantly decreased in low dose group and significantly increased in high dose group. The mRNA expression levels of five subtypes of CYP450 enzymes in rat liver were decreased in high dose and low dose groups in a dose-dependent manner. Especially the high dose processed P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in rats. The study showed that high dose P. multiflorum water extract had hepatotoxicity, and the degree of liver damage was increased with the increase of dose. It shall be noted that 5.40 g•kg⁻¹ water extract of P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in the liver of rats.

Emerging application and reflections of cell membrane chromatography in the quality evaluation of traditional Chinese medicine / 药学学报

Cell membrane chromatography (CMC) was first proposed by Professor He in 1996. As one of bio-affinity chromatography technique, CMC was a simple and convenient technology in the study of interactions of active components in traditional Chinese medicines (TCMs) with membrane receptors in vitro, and screen active components from complicated TCMs. Recently, the CMC technology was developed rapidly, and widely applied in the discovery of lead compounds from nature product. This review article is focused on the application of cell membrane chromatography in the identification of active components in traditional Chinese medicine, together with the recent development of CMC methodology. Combining with our previous works in the analysis of the composition of complex substances, biochromatography and TLC bioautography for quality evaluation of TCM, we proposed a new holistic quality evaluation strategy of TCM related with bioactivity, which could be summarized as the integration of screen (screening of quality control marker by CMC), macroscopic characterization (characterizing the chemical material basis by multi-dimension and multi data fingerprinting) and microscopic description (multi-component quantification). The proposed strategy would provide a new idea for the holistic quality evaluation of TCM in the composition and concentration of bioactive components as quality evaluation indicators.

Molecular mechanism of Xuebijing injection in treatment of sepsis according to “drug-target-pathway” network / 药学学报

This study was aimed to construct a “drug-target-pathway” network of Xuebijing injection for sepsis treatment in an effort to explore the “multi-components, multi-targets, multi-pathways” mechanism based on “system-system” research mode. Active ingredients of Xuebijing injection were used to predict the potential targets according to reversed pharmacophore matching method. The pathway information was acquired from DAVID and KEGG database. The Cytoscape software was used to construct the “ingredient-target-pathway” network of Xuebijing injection for sepsis treatment. The results showed that 21 major active ingredients of Xuebijing injection regulated 550 targets (HRAS, GSK3B, BTK, AK, et al) and affected 10 inflammation and immune-related pathways, such as B cell receptor signaling pathway, VEGF signaling pathway, natural killer cell mediated cytotoxicity, Toll-like receptor signaling pathway. The sepsis therapeutic effect of Xuebijing injection reflected the action features of traditional Chinese medicine as multi-ingredients, multi-targets, multi-pathways. This research clarifies the material basis of Xuebijing injection for anti-inflammation and immunoregulation, providing a scientific basis for elucidation the mechanism of Xuebijing injection in the treatment of sepsis.

The mechanism of rosiglitazone compound based on network pharmacology / 药学学报

Applications of network pharmacology are increasingly widespread and methods abound in the field of drug development and pharmacological research. In this study, we choose rosiglitazone compound as the object to predict the targets and to discuss the mechanism based on three kinds of prediction methods of network pharmacology. Comparison of the prediction result has identified that the three kinds of prediction methods had their own characteristics: targets and pathways predicted were not in accordance with each other. However, the calcium signaling pathway could be predicted in the three kinds of methods, which associated with diabetes and cognitive impairment caused by diabetes by bioinformatics analysis. The above conclusion indicates that the calcium signaling pathway is important in signal pathway regulation of rosiglitazone compound, which provides a clue to further explain the mechanism of the compound and also provides a reference for the selection and application of methods of network pharmacology in the actual research.

Study on inhibitory effects and mechanism of lipophilic components in Salvia miltiorrhiza on angiogenesis in vitro / 中国中药杂志

In this study, the human umbilical vein endothelial cell model was used to study the regulating effect of lipophilic components in Salvia miltiorrhiza on angiogenesis, and explore its possible mechanism. The cell model was established to determine the effect of lipophilic components in S. miltiorrhiza on the proliferative activity and migration capacity of endothelial cells. Then the realtime fluorescence quantification PCR technology was applied to detect the changes in the gene expressions of angiogenesis-related cytokines VEGF-A, VEGF-C and MMP-9. The results showed that 5 mg x L(-1) lipophilic components in S. miltiorrhiza could inhibit the proliferation and migration of endothelial cells, and reduce the expression of VEGF-A and MMP-9 genes. It indicated that lipophilic components in S. miltiorrhiza may inhibit the proliferation and migration of endothelial cells by inhibiting the expression of VEGF-A and MMP-9 genes, so as to show the inhibitory effect on angiogenesis.

Synergistic effect and mechanism of cineole and terpineol on in-vitro transdermal delivery of Huperzine A from microemulsions

The aim of the present study was to investigate the influence and the mechanisms of cineole and terpineol on the in-vitro transdermal delivery of huperzine A from microemulsions, and their potential synergistic effect on the permeation enhancement. The transdermal delivery of huperzine A from microemulsions with different concentrations of cineole and terpineol through the rat abdominal skin was determined by Franz-type diffusion cells. The partition coefficient of huperzine A between the full thickness skin and microemulsion was determined. Attenuated total reflection-Fourier transform infrared spectroscopy [ATR-FTIR] was carried out to analyze the effects of cineole and terpineol on the biophysical properties of the stratum corneum [SC] and the mechanisms of permeation enhancement. These results indicated that cineole and terpineol could synergistically increase the transdermal delivery of huperzine A from microemulsions through increasing the partition and diffusion coefficients of huperzine A. ATR-FTIR studies further validated the synergistic effect and revealed that the enhancing mechanisms were due to increasing the disorderliness and fluidity of SC lipid alkyl chains, disrupting the structure of keratin in SC, and extracting SC lipids. In conclusion, cineole and terpineol, acting synergistically to enhance the transdermal delivery of huperzine A from microemulsions, might provide an alternative permeation enhancer combination for the transdermal delivery of huperzine A

Therapeutic effects of gegen qinlian decoction and its mechanism of action on type 2 diabetic rats / 药学学报

The objective of this study is to fully investigate the therapeutic effect and mechanisms of action of Gegen Qinlian decoction (GD) on type 2 diabetes mellitus (type 2 DM). A rat model of type 2 DM was established with the combination of high-fat diet and multiple low doses of streptozotocin (STZ). Biochemical indicators related to glucose metabolism disorders, insulin resistance, oxidative stress were observed. The type 2 DM rats were administrated with GD for 80 days, the above-mentioned indexes were detected. The results indicated that the hepatic glycogen synthesis level was promoted, fasting blood glucose level and fasting blood insulin level were significantly reduced, insulin sensitivity index was significantly improved; the level of superoxide dismutase (SOD) was increased and the level of malondialdehyde (MDA) was reduced; pathologic morphology of pancreas and kidney was ameliorated in the GD group. It was indicated that the therapeutic mechanisms of action of GD on type 2 DM might be related to its effect of ameliorating glucose metabolism disorders, relieving insulin resistance, increasing the tissues' sensitivity to insulin, improving the antioxidative ability of living system, GD has therapeutic effect on type 2 DM and protective effects against damaged pancreatic function.

High-throughput pyrosequencing of the complete chloroplast genome of Magnolia officinalis and its application in species identification / 药学学报

Chloroplast genome sequences have comprehensive application prospects in DNA barcoding and chloroplast engineering in traditional Chinese medicine. The complete chloroplast genome of Magnolia officinalis sequenced by high-throughput pyrosequencing and a sequencing procedure was established. Fourteen contigs were obtained after de nove assembly. The sequencing percent of coverage was 99.99%. The chloroplast genome is 160 183 bp in size, and has a typical quadripartite structure with the large (LSC, 88 210 bp) and small copy (SSC, 18 843 bp) regions separated by two copies of an inverted repeat (IRs, 26 565 bp each). chloroplast genes were successfully annotated, of which 17 genes located in each IR region. The chloroplast genome features in Magnolia officinalis are nearly identical to those from other Magnoliid chloroplast genomes. Phylogenetic analyses were performed based on 81 shared coding-genes for a total of 9 Magnolia samples of 5 closely related species. Results showed that distinguishing among species was generally straightforward at the species and population level. This study confirmed the effectiveness of our chloroplast genome sequencing procedure. The chloroplast genome can provide distinguishing differences to help identify Magnolia officinalis and its closely related plants.

Comparative study on chemical quality of main species of epimedium / 药学学报

This study was to comprehensively evaluate the chemical quality of main species of epimedium planted in China. The contents of 5 marker compounds, epimedin A, epimedin B, epimedin C, icariin and baohuoside I, as well as total flavonoids of 22 samples of 8 officinal species of Epimedium were determined by HPLC and UV, separately. Some physical and chemical tests (H2O, total ash, acid-insoluble ash and EtOH extract) were also carried out to investigate their chemical qualities. There were significant differences in types and contents of prenyl-flavonoid glycosides such as epimedin A, epimedin B, epimedin C, icariin and baohuoside I in different species, meanwhile, the physical and chemical parameters results also showed that there were obvious differences in chemical quality among different species of epimedium herb. The results provide theoretical and experimental basis for the establishment of comprehensive quality assessment system of epimedium in China.

Tissue distribution of arsenic of liushen pills and realgar / 药学学报

This study is to report the tissue distribution of arsenic after giving different doses of realgar and Liushen pills to Beagle dogs, in order to provide basis for the safety evaluation of Liushen pills. ICP-MS was used to measure arsenic concentration, and HPLC-ICP-MS was used to analyze arsenic speciation. The concentration of total arsenic and As(III) + DMA (arsenite + dimethylarsenic acid) increased with dosing of realgar. Total arsenic concentration in most tissues and As(III) + DMA concentration in all tissues of Liushen pills group are lower than that of realgar group, but AsB concentration in liver, spleen and kidney of Liushen pills group increased. The concentration of total arsenic showed a dose-dependent manner with dosage administered. It was indicated that components in Liushen pills can reduce solubility of arsenic in realgar, which may decrease toxicity of realgar.

Effect of tangshen formula on phospholipids metabolism in diabetic nephropathy patients / 药学学报

This study was to report the effect of Tangshen Formula on phospholipids metabolism in diabetic nephropathy patients. A normal phase-HPLC-TOF/MS method was used in this study for the determination of seven species of phospholipids in human plasma. Then, the concentration changes of potential phospholipids biomarkers were discussed in diabetic nephropathy phase III and phase IV patients among different groups, including before and 3, 6 months after administration of Tangshen Formula. Significant increases of PE750, PI885, PC792, PC826, PC830, PC854 and PC802 levels were observed 6 months after administration of Tangshen Formula and conventional western medicine, as well as a decrease of LPC540 level, when compared with those before medication. Concentrations of all the potential phospholipids biomarkers showed a tendency towards normal levels; however, both the improvement degree and onset time of these compounds were not same. Additionally, Tangshen Formula treatment based on conventional western medicine treatment was more efficient in adjusting the levels of these compounds when compared with western medicine treatment alone, especially for the phase IV patients. These results indicated that Tangshen Formula was capable in regulating and improving phospholipids metabolism in diabetic nephropathy patients, which may be related with the direct or indirect inhibition of protein kinase C pathway and the corresponding reduction of phospholipase A2 activity. Therefore, Tangshen Formula may be used as an effective drug for diabetic nephropathy therapy, at least as an adjunctive therapeutic drug.

Basic experimental and clinical research on peritoneal dialysis in the past 16 years / 中南大学学报(医学版)

To summarized the experiences from our basic experimental and clinical research on peritoneal dialysis. In the past 16 years, peritoneal fibrosis rat models and rabbit models of peritonitis were first established successfully in our laboratory in China. Peritoneal mesothelial cells were also separated and identificated. Besides, we assessed the biocompatibility of peritoneal dialysis fluid and analyzed the molecular mechanism of peritoneal mesothelial cell injury. We demonstrated the key role of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF) and peroxisome proliferative activated receptor-gamma (PPAR-gamma) in the pathogenesis of peritoneal fibrosis, as well as their regulation of molecular mechanism. Furthermore, we transfected the plasmids encoding TGF-beta1-shRNA or pCTGF-shRNA into peritoneal cells and tissues by nanocarrier technologies. In clinical research, the positioning of peritoneal dialysis catheters, peritoneal dialysis treatment modalities and the prevention and treatment of its complications were studied. The characteristics and mechanism of solute transport in peritoneal dialysis was also explored.

Integration of metabonomics technology and its application in modernization of traditional Chinese medicine / 药学学报

Metabonomics technology has been widely applied in the field of biology and pharmacy nowadays. The integration on mass spectrometry, nuclear magnetic resonance, and other modern analytical techniques, made up of the metabonomics technology platform, have accelerated the study on metabonomics. In this paper, the past results of metabonomics studies are reviewed, and the applications of metabonomics to traditional Chinese medicine are prospected.

Determination of loganin and paeonol in Liuwei Dihuang pills by HPLC amalgamated of double UV waves / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a high performance liquid chromatographic (HPLC) amalgamated to double UV waves method for simultaneous determination of loganin and paeonol in Liuwei Dihuang pills.</p><p><b>METHOD</b>A HPLC method was developed. The separation was carried out on a Agilent Zorbax SB C18 column (5 microm, 4.6 mm x 250 mm). The mobile phase consisted of water (A) and acetonitrile (B) with linear linear gradient elution [0-8 min, (B) from 1% to 12%; 8-21 min, B keep 12%; 21-40 min, (B) from 12% to 90%; 40-50 min, B keep 90% for 10 min]. The detection was Photodiode Array with the detection wavelengths were at 236 nm and 274 nm. The column temperature being 30 degrees C and the flow rate was 1.0 mL min(-1). Extracting the chromatergraph from 274 nm and 236 nm, we amalgamated the two chromatographs by matlab programmed.</p><p><b>RESULT</b>The calibration curves of loganin and paeonol were linear in the ranges of 0.0362-1.09 microg (r =0. 9998) and 0.0450-1.35 microg (r =0.9998), respectively. The average recoveries of loganin and paeonol were 97.3% (RSD 1.4 %) and 103.0% (RSD 1.9%), respectively. Three different batches of Liuwei Dihuang pills were determined with this method.</p><p><b>CONCLUSION</b>This is a more convenient, reasonable and credible quality control method for the traditional Chinese medicine.</p>