Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro / 中国中药杂志

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

Incidence of coexistence of multiple diseases in patients over 65 years of age and its impact on the risk of death in hospital / 公共卫生与预防医学

Objective To investigate the incidence of multiple disease coexistence in emergency department patients over 65 years old and its impact on the risk of death in hospital, so as to provide theoretical basis for reducing the risk of death in emergency department patients over 65 years old. Methods From January 2019 to January 2020, elderly patients over 65 years old who received emergency treatment in our hospital were selected as subjects to analyze the coexistence of multiple diseases. The information of current disease, blood pressure, blood glucose level and other potential influencing factors, as well as the incidence of hospitalization after emergency treatment were collected, and the factors influencing the risk of death in hospital were analyzed and discussed. Results During the study period, there were 1 195 patients over 65 years old, including 469 patients with multi-disease coexistence (excluding malignant tumors), with an incidence rate of 39.25%. Among the elderly patients in the emergency department, the top four diseases with multiple coexisting diseases are as follows: ischemic stroke (43.92%), acute myocardial infarction (24.95%), hemorrhagic stroke (16.84%), and falls (11.30%). In addition, “ischemic stroke + hypertension + diabetes + coronary heart disease” accounted for the highest proportion (42.22%) in the combination of multi-disease coexisting diseases, followed by "myocardial infarction + ischemic stroke + hypertension + Diabetes + coronary heart disease” (21.11%), and the third in the composition ratio was “fall + ischemic stroke + hypertension + diabetes + coronary heart disease” (0.66%). Among the 469 patients with multi-disease coexistence, a total of 68 died during hospitalization after emergency department; 469 patients were divided into two groups: the dead and the survivors, and the potential factors affecting the risk of death were analyzed. The multivariate regression analysis showed that male (OR=1.485 , P<0.001), age over 80 years (OR=3.090, P<0.05), more than four types of comorbidities (OR=4.407, P<0.001), BMI level showed weight loss (OR=4.366, P<0.001) and Comorbidities included hypertension (OR=3.564, P<0.001) as a potential risk factor, which would increase the risk of death; while normal blood pressure (OR=0.581, P<0.001) might potentially reduce the risk of death. Conclusion Special attention should be paid to the elderly patients over 65 years old who are male, over 80 years old, thin and with many types of comorbidities (more than four types), especially those with hypertension at the same time, in order to reduce hospitalization after emergency department risk of death during the period.

Chemical composition analysis and value evaluation of stems and leaves of Astragalus membranaceus var. mongholicus / 中国中药杂志

This study aimed to provide data support for resource utilization of the stems and leaves of Astragalus membranaceus var. mongholicus(SLAM) by analyzing and evaluating the chemical constituents. The crude protein, crude fiber, and soluble saccharide of SLAM were analyzed by Kjeldahl method, filtration method, and UV-Vis spectrophotometry, respectively. The nucleosides, amino acids, flavonoids, and saponins of SLAM were analyzed by ultraperformance liquid chromatography-triple quadrupole mass spectrometry(UPLC-TQ-MS). Combined with principal component analysis(PCA), the quality difference of resource components of SLAM was comprehensively evaluated. The results showed that the average content of crude protein, crude fiber, total polysaccharide, and redu-cing sugar in SLAM was 5.11%, 30.33%, 11.03 mg·g~(-1), and 31.90 mg·g~(-1), respectively. Six nucleosides, 15 amino acids, 22 flavonoids, and one saponin were detected, with an average content of 1.49 mg·g~(-1), 6.00 mg·g~(-1), 1.86 mg·g~(-1), and 35.67 μg·g~(-1), respectively. The content of various types of chemical components in SLAM differed greatly in different harvesting periods and growing years. The results of PCA showed that the quality of SLAM produced in Ningxia was superior. The results can provide references for the utilization of SLAM.

Tenuifolin in Treatment of Dementia： A Review / 中国实验方剂学杂志

Tenuifolin， a main component in Polygalae Radix， is frequently used as an important indicator for quality control of Polygalae Radix and its processed products. Dementia is a serious and persistent cognitive disorder， and the number of dementia patients is increasing worldwide， which brings great economic burden and mental pressure to families and society. At present， cholinesterase inhibitor and other drugs can only alleviate the symptoms of dementia， and there are some toxic and side effects. It has been found that tenuifolin can significantly improve cognitive disorder， learning and memory and is expected to be a potential drug for treating dementia. Tenuifolin exerts protective effects on amyloid-β （Aβ） deposition， acetylcholine reduction， neuroinflammation， cellular oxidative damage and nerve cell apoptosis caused by neurodegenerative diseases via multiple mechanisms， and can be applied to various types of dementia. In addition， it can be quickly absorbed into the blood， mainly distributed in liver and kidney， and can enter into the brain through the blood-brain barrier. However， because of its large molecular mass and poor fat solubility， tenuifolin can be rapidly eliminated， generating some problems such as low oral absoBrbability and permeability of blood-brain barrier. Therefore， the information of chemistry， pharmacology， pharmacokinetics and toxicology of tenuifolin was summarized in this paper to provide reference and ideas for further research and application.

Determination of eight active components of Bufei Huoxue Capsules in rat plasma and their pharmacokinetics by UHPLC-MS/MS / 中国中药杂志

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established to investigate the pharmacokinetic behaviors of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone in rat plasma after oral administration of Bufei Huoxue Capsules. After SD rats were administered with Bufei Huoxue Capsules suspension by gavage, blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm). The mobile phase consisted of acetonitrile(A) and water(B) containing 0.1% formic acid in gradient elution. The positive and negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 3.2.8. Psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone were detected in the rat plasma after drug administration, with AUC_(0-t) of(3 357±1 348),(3 555±1 696),(3.03±0.88),(2.21±0.33),(1 787±522),(2 295±539),(5.69±1.41) and(3.40±0.75) μg·L~(-1)·h, and T_(max) of(1.56±0.62),(1.40±0.70),(0.21±0.05),(0.25±0.12),(0.26±0.11),(0.34±0.29),(0.74±0.59), and 0.25 h. The method is proved specific and repeatable and is suitable for the determination of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, pso-ralen, isopsoralen, methylnissolin, and neobavaisoflavone in the rat plasma, which can be applied to pharmacokinetic study.

DNA methylation diversity analysis of Lycium barbarum samples from different cultivation areas based on MSAP / 中国中药杂志

Obvious epigenetic differentiation occurred on Lycium barbarum in different cultivation areas in China. To investigate the difference and change rule of DNA methylation level and pattern of L. barbarum from different cultivation areas in China, the present study employed fluorescence-assisted methylation-sensitive amplified polymorphism(MSAP) to analyze the methylation level and polymorphism of 53 genomic DNA samples from Yinchuan Plain in Ningxia, Bayannur city in Inner Mongolia, Jingyuan county and Yumen city in Gansu, Delingha city in Qinghai, and Jinghe county in Xinjiang. The MSAP technical system suitable for the methylation analysis of L. barbarum genomic DNA was established and ten pairs of selective primers were selected. Among amplified 5'-CCGG-3' methylated sites, there were 35.85% full-methylated sites and 39.88% hemi-methylated sites, showing a high degree of epigenetic differentiation. Stoichiometric analysis showed that the ecological environment was the main factor affecting the epigenetic characteristics of L. barbarum, followed by cultivated varieties. Precipitation, air temperature, and soil pH were the main ecological factors affecting DNA methylation in different areas. This study provided a theoretical basis for the analysis of the epigenetic mechanism of L. barbarum to adapt to the diffe-rent ecological environments and research ideas for the introduction, cultivation, and germplasm traceability of L. barbarum.

Effect and Mechanism of Didangtang on NLRP3 Inflammasomes in Diabetic Cardiomyopathy Mice / 中国实验方剂学杂志

Objective:To investigate the effects of different doses of Didangtang on myocardial inflammatory lesions in diabetic mice. Method:Sixty C57BL/6J mice were randomly divided into normal group （<italic>n</italic>=10） and model group （<italic>n</italic>=50）. The diabetic mice in the model group were established by intraperitoneal injection of high-fat diet combined with streptozotocin （STZ）. After model reproducing， the mice were fed with high-fat diet. After 8 weeks， the cardiac function of the mice was detected by using an ultrasound imaging platform. If the cardiac function decreased， the diabetic cardiomyopathy mice were modeled successfully. The nonmodel mice were eliminated， and finally 40 model mice were modeled. The rats in the model group were randomly divided into model group， low， medium and high dose of Didangtang group（1.5，3，6 g·kg^-1） and simvastatin group（0.001 5 g·kg^-1） according to heart function， with 8 rats in each group. The cardiac function of mice was detected by ultrasound imaging platform， fiber bragg grating（FBG）， triglyceride（TG） and total cholesterol（TC） were detected by automatic biochemical analyzer， hematoxylin-eosin （HE） staining was used to observe the pathological changes of myocardium， and the levels of NOD-like receptor3（NLRP3）， thiomdoxin interaction protein（TXNIP）， cysteinyl aspartate specific proteinase-1（Caspase-1） and Interleukin-1<italic>β</italic>（IL-1<italic>β</italic>） in myocardial tissue， as well as the content of reactive oxygen species（ROS） were detected by Western blot. Result:Compared with the normal control group， the levels of FBG， TC and TG in the model group significantly increased （<italic>P</italic><0.01）； the values of EF and FS significantly decreased （<italic>P</italic><0.01）； the expression of ROS significantly increased （<italic>P</italic><0.05）， and the expressions of NLRP3， TXNIP， Caspase-1 and IL-1<italic>β</italic> in the myocardial tissue significantly increased （<italic>P</italic><0.05）. Compared with the model group， the levels of FBG， TC and TG in the middle and high dose groups of Didangtang and simvastatin groups significantly decreased （<italic>P</italic><0.05）； the EF and FS in each dose group and simvastatin group improved （<italic>P</italic><0.05）， and the change in the middle dose group was more obvious （<italic>P</italic><0.05）. HE staining showed that Didangtang could improve the pathological changes of myocardial tissue in mice， the ROS expression levels of mice in each dose group of Didangtang and simvastatin group significantly reduced， especially in the middle dose group， the expression levels of NLRP3， TXNIP， Caspase-1 and IL-1<italic>β</italic> in each dose group significantly decreased， and the effect of middle dose of Didangtang on reducing expressions of NLRP3， TXNIP and Caspase-1 in myocardial tissue was more obvious， the effect of high dose of Didangtang on reducing the expression of IL-1<italic>β</italic> in myocardial tissue was more obvious. Conclusion:Didangtang can improve myocardial inflammatory lesions in diabetic cardiomyopathy mice by inhibiting the activation of NLRP3 inflammasome.

Regulatory effect of total phenolic acid from the stems and leaves of Salvia miltiorrhiza Bge. on intestinal microflora and short-chain fatty acids in type 2 diabetic nephropathy mice / 药学学报

To study the regulating effect of total phenolic acids from the stems and leaves of Salvia miltiorrhiza Bge. on the intestinal flora and short-chain fatty acids in spontaneous type 2 diabetic nephropathy mice, db/db mice were taken as the research object, and were treated with the total phenolic acid of Salvia miltiorrhiza Bge. Animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine Drug Safety Evaluation Research Center. Fresh feces and cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. Gas chromatography was used to detect short-chain fatty acids in fresh feces and cecal content. Then the correlation analysis of the two results was made. Compared with the normal group, the most significant decreased differential flora in the model group were g_Rikenellaceae_ RC9_gut_group and g_Bacteroidales_S24-7_group, while the most significant increased were g_unclassified_f__ Coriobacteriaceae and g_unclassified_p__Firmicutes. Compared with the blank group, the contents of isovaleric acid and valeric acid in fresh feces and the contents of 6 short-chain fatty acids in the cecal contents of the model group were significantly reduced (P < 0.01). After drug intervention, the intestinal flora disorder and the reduction of short-chain fatty acids were improved to varying degrees, and the effect of the total phenolic acids from the stems and leaves of Salvia miltiorrhiza Bge. was slightly better than that from the roots in regulating some flora and short-chain fatty acids. The results of correlation analysis showed that g_Rikenellaceae_RC9_gut_group was moderately positively correlated with acetic acid and isobutyric acid in the cecal contents (r > 0.4). It is suggested that the total phenolic acid from the stems and leaves of Salvia miltiorrhiza Bge. can improve the intestinal flora disorder of mice with type 2 diabetic nephropathy, and can regulate the content of short-chain fatty acids in the intestine via adjusting the content of some short-chain fatty acid-producing bacteria, thereby helping to restore normal.

Mechanism of Olibanum-Myrrha in treatment of rheumatoid arthritis based on network pharmacology and molecular docking / 中国中药杂志

In this paper, network pharmacology method and molecular docking technique were used to investigate the target genes of Olibanum and Myrrha compatibility and the possible mechanism of action in the treatment of rheumatoid arthritis(RA). Our team obtained the main active components of Olibanum-Myrrha based on literatures study, relevant traditional Chinese medicine systematic pharmacological databases and literature retrieval, and made target prediction of the active components through SwissTargetPrediction database. At the same time, RA-related targets were collected through DrugBank, GeneCards and Therapeutic Target Database(TDD) databases; and VENNY 2.1 was use to collect intersection targets to map common targets of drug and disease of Venn diagram online. The team used STRING database to construct PPI protein interaction network diagram, and screen out core targets according to the size of the interaction, and Cytoscape 3.6.0 software was used to construct network models of "traditional Chinese medicine-component-target" "traditional Chinese medicine-component-target-disease" and core target interaction network model. The intersection target was analyzed by using DAVID 6.8 online database for GO function analysis and KEGG pathway enrichment analysis, and Pathon was used to visualization. AutoDock Vina and Pymol were used to connect the core active components with the core targets. Sixteen active components of Olibanum-Myrrha pairs were found and collected in the laboratory, and 320 relevant potential targets, 468 RA-related targets and 62 intersection targets were obtained through the Venn diagram. It mainly acted on multiple targets, such as IL6, TNF, IL1 B and MAPK1, involving TNF signaling pathway and Toll-like receptor signaling pathway in RA treatment. Finally, in this study, possible targets and signaling pathways of Olibanum-Myrrha compatibility therapy for RA were discussed, and molecular docking between core targets and core active components was conducted, which could provide scientific basis for the study on the mechanism of Olibanum-Myrrha compatibility.

Identification of metabolites of Zhali Nusi Prescription in rat plasma, bile, urine and feces after oral administration / 中国中药杂志

This study was designed to determine the metabolites of Zhali Nusi Prescription(ZLNSP) in rats. The ultra-high performance liquid chromatography-LTQ Orbitrap mass spectrometric(UHPLC-LTQ-Orbitrap-MS) and mass defect filter techniques were applied to analyze the metabolites of ZLNSP in rat plasma, bile, urine and feces. The biological samples were analyzed by ACQUITY UPLC BEH T_3 column(2.1 mm×100 mm,1.7 μm), with 0.1% formic acid water(A)-acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). An analytical method for biological samples of rats was established, and 8 prototype components and 36 metabolites were identified. The results showed that the metabolic pathways of the main components of ZLNSP in rats included methylation, glucuronidation, sulfation and so on. It provi-ded information for the therapeutic effect of ZLNSP in vivo.

Research thoughts and methods on grading identification and transmission change law of traditional Chinese medicine(TCM) Q-marker / 中国中药杂志

The quality marker( Q-maker) of traditional Chinese medicine( TCM) has been the core concept of TCM quality evaluation and control in recent years. Based on the knowledge and long-term practice of the researches on TCM quality,we put forward that " Taking the effectiveness as the core,the measurability and peculiarity as necessary conditions,and considering compatibility for TCM formulae,TCM Q-makers are selected and confirmed,and then the transmission and traceability should be investigated as its functional attributes". Selecting the commonly used representative TCM as the research object,based on the score of TCM effectiveness,measurability and peculiarity,a layered three-dimensional integrated technology was adopted for the quantitative evaluation and grading identification of the Q-markers for TCM. And after Q-markers for TCM are selected and confirmed,the transmission variation of the Q-markers is studied in the whole process from the formation of TCM to its function representation. Based on TCM chemical and biological characteristics as well as effectiveness,and integrating multidisciplinary techniques and methods,researches on innovative methods for system identification and confirmation of the TCM Q-makers are developed emphatically to form representative and exemplary extensive application,which will provide significant theoretical and methodological support for effectively improving the quality control level of TCM.

Value of fasting plasma glucose to screen gestational diabetes mellitus before the 24th gestational week in women with different pre-pregnancy body mass index / 中华医学杂志(英文版)

BACKGROUND@#Gestational diabetes mellitus (GDM) is usually diagnosed between 24th and 28th gestational week using the 75-g oral glucose tolerance test (OGTT). It is difficult to predict GDM before 24th gestational week because fast plasma glucose (FPG) decreases as the gestational age increases. It is controversial that if FPG ≥5.1 mmol/L before 24th gestational week should be intervened or not. The aim of this study was to evaluate the value of FPG to screen GDM before 24th gestational week in women with different pre-pregnancy body mass index (BMI).@*METHODS@#This was a multi-region retrospective cohort study in China. Women who had a singleton live birth between June 20, 2013 and November 30, 2014, resided in Beijing, Guangzhou and Chengdu, and received prenatal care in 21 selected hospitals, were included in this study. Pre-pregnancy BMI, FPG before the 24th gestational week, and one-step GDM screening with 75 g-OGTT at the 24th to 28th gestational weeks were extracted from medical charts and analyzed. The pregnant women were classified into four groups based on pre-pregnancy BMI: Group A (underweight, BMI < 18.5 kg/m), Group B (normal, BMI 18.5-23.9 kg/m), Group C (overweight, BMI 24.0-27.9 kg/m) and Group D (obesity, BMI ≥28.0 kg/m). The trend of FPG before 24th week of gestation was described, and the sensitivity and specificity of using FPG before the 24th gestational week to diagnose GDM among different pre-pregnancy BMI groups were reported. Differences in the means between groups were evaluated using independent sample t-test and analysis of variance. Pearson Chi-square test was used for categorical variables.@*RESULTS@#The prevalence of GDM was 20.0% (6806/34,087) in the study population. FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. FPG was higher in women with higher pre-pregnancy BMI. FPG before the 24th gestational week and pre-pregnancy BMI could be used to predict GDM. The incidence of GDM in women with FPG ≥5.10 mmol/L in the 19th to 24th gestational weeks and pre-pregnancy overweight or obesity was significantly higher than that in women with FPG ≥5.10 mmol/L and pre-pregnancy BMI <24.0 kg/m (78.5% [62/79] vs. 52.9% [64/121], χ = 13.425, P < 0.001).@*CONCLUSIONS@#FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. Pre-pregnancy overweight or obesity was associated with an increased FPG value before the 24th gestational week. FPG ≥5.10 mmol/L between 19 and 24 gestational weeks should be treated as GDM in women with pre-pregnancy overweight and obesity.

Modern research approaches and strategies for compatibility effects and efficacy components of herbal pairs / 药学学报

The herb pair is the simple and exquisite experience summary accumulated by generations of traditional Chinese medicine (TCM) experts in the process of long-term herbal prescription for curing diseases. Although it is only a combination of two herbs, it is cleverly matched and properly proportioned, which can well interpret TCM characteristics of "great combination and artful application". Moreover, the herb pair is an intermediate point between single herb and several TCM formulae, which implicates certain regularity and some connotation of many TCM formulae for diagnosis and treatment based on an overall analysis of the illness and the patient's condition. Our team has long been focusing on the complexity of drug interactions and the diversity of TCM components to carry out systematic research on herb pair by using modern scientific and technological knowledge and approaches. As results, a series of modern research approaches and strategies formed for the compatibility effect and bio-active components of the herb pair. By representing the principles and application characteristics of these approaches, this paper provides important support for elucidating scientific connotation of compatibility regularity of herb pairs and application of formulae optimization, as well as explorative ideas and approaches for modern research on other herb pairs.

Interaction of Scutellaria-Coptis herb pair in improvement of glucose and lipid metabolism of type 2 diabetes rats based on response surface method / 药学学报

The response surface method was used to evaluate the concentration range, property and degree of Scutellaria (HQ) and Coptis (HL) herb pair on improvement of glucose and lipid metabolism in this paper. Type 2 diabetes mellitus (T2DM) was induced in rats by low a dose of streptozotocin (STZ) in combination with high-fat diet feeding. The rats were administered with HQ-HL extract pairs at different ratio (1:0, 3:1, 2:1, 3:2, 1:1, 2:3, 1:2, 1:3, 0:1). To investigate the influence of herb pair extracts on glucose and lipid metabolism of T2DM rats, the multi index synthetic index method was adopted to integrate the indexes, then the response surface method was applied to analyze the integration results. The ratio of HQ and HL from 3:1 to 1:3 showed a synergistic effect (with the value between -0.2 and -0.8). Especially, when the proportion was between 3:2 and 1:3, herb pair extracts possessed stronger synergistic effects (value:-0.8). The high dose of HQ-HL with the ratio of 1:1 exhibited the strongest synergistic effect.

Pharmacokinetics of Mori Folium flavones and alkaloids in normal and diabetic rats / 中国中药杂志

To study the pharmacokinetic effect of Mori Folium flavones and alkaloids in normal and diabetic rats. An UPLC-TQ-MS method was developed for the simultaneous determination of rutin, isoquercitrin, astragalin, kaempferol, quercetin, chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, DNJ and fagomine in plasma of rats. The diabetic rat model was induced through intravenous injection with alloxan and high-fat diet. Samples of plasma of rats were obtained at different time points, after the rats were administrated with Mori Folium flavones and alkaloids. After the deproteinization with acetonitrile, the concentrations of Mori Foliam constituents in rats at different time points were detected by UPLC-TQ-MS method, and pharmacokinetic parameters were calculated by DAS 2.0 software. The results showed that quercetin and kaempferol reached peak at 0.333 h, indicating that Mori Folium flavonoid constituents were absorbed and distributed quickly. At about 4 h after administration, both of them reached the peak concentrations for the second time, suggesting that they stayed in intestine for a long time. DNJ and fagomine in gastrointestinal tract can be quickly absorbed into blood, and the concentration in plasma reached peak after 0.667 h, suggesting that both of them could be rapidly distributed in the systemic circulation of rats. Cryptochlorogenic acid, neochlorogenic acid, quercetin, kaempferol and rutin were found to have a higher Cmax and AUC0-t in normal rats than those in diabetic rats. The t1/2values of cryptochlorogenic acid and neochlorogenic acid were shorter in diabetic rats, while quercetin, kaempferol and rutin had a longer t1/2value in diabetic rats. Chlorogenic acid, astragalin, isoquercitrin, fagomine had a higher Cmax in diabetic rats, and the t1/2values of astragalin and fagomine were longer, which suggested differences in absorption of active ingredients under normal and diabetic conditions.

Comparative study on promoting blood effects of Danshen-Honghua herb pair with different preparations based on chemometrics and multi-attribute comprehensive index methods / 中国中药杂志

To evaluate the promoting blood circulation and removing blood stasis effects of Danshen-Honghua(DH) herb pair with different preparations (alcohol, 50% alcohol and water) on blood rheology and coagulation functions in acute blood stasis rats, and optimize the best preparation method of DH based on principal component analysis(PCA), hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods. Ice water bath and subcutaneous injection of adrenaline were both used to establish the acute blood stasis rat model. Then the blood stasis rats were administrated intragastrically with DH (alcohol, 50% alcohol and water) extracts. The whole blood viscosity(WBV), plasma viscosity(PV), erythrocyte sedimentation rate(ESR) and haematocrit(HCT) were tested to observe the effects of DH herb pair with different preparations and doses on hemorheology of blood stasis rats; the activated partial thromboplastin time(APTT), thrombin time(TT), prothrombin time(PT), and plasma fibrinogen(FIB) were tested to observe the effects of DH herb pair with different preparations on blood coagulation function and platelet aggregation of blood stasis rats. Then PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods were all used to comprehensively evaluate the total promoting blood circulation and removing blood stasis effects of DH herb pair with different preparations. The hemorheological indexes and coagulation parameters of model group had significant differences with normal blank group. As compared with the model group, the DH herb pair with different preparations at low, middle and high doses could improve the blood hemorheology indexes and coagulation parameters in acute blood stasis rats with dose-effect relation. Based on the PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods, the high dose group of 50% alcohol extract had the best effect of promoting blood circulation and removing blood stasis. Under the same dose but different preparations, 50% alcohol DH could obviously improve the hemorheology and blood coagulation function in acute blood stasis rats. These results suggested that DH herb pair with different preparations could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats, and the optimized preparation of DH herb pair on promoting blood effects was 50% alcohol extract, providing scientific basis for more effective application of the DH herb pair in modern clinic medicine.

Expression of NADPH Oxidase2 in gastric cancer and its correlation with the vascular endothelial growth factor level / 中国现代普通外科进展

Objective:To investigate the expression of NADPH Oxidase2 (NOX2) in gastric cancer tissues and its correlation with vascular endothelial growth factor(VEGF) level.Methods:The gastric cancer tissue and the adjacent tumor tissue were obtained from the patients who received radical operation for gastric cancer during July 2014 to July 2015 in Provincial Hospital Affiliated to Shandong University.The expression of NOX2 in the tumor tissue and the adjacent tissue were detected by the immunohistochemistry(IHC) and Western blot.The VEGF level were detected by IHC in gastric cancer tissues.The spearman rank correlation were used to detected the correlation between the NOX2 and VEGF.Results:The positive expression rate of NOX2 in gastric cancer tissue was 47.2％ (58/123),and the positive expression rate in the adjacent tissue was 8.13％ (10/123),mostly expression in the adjacent was weak positive.The outcome of Western blot show that the NOX2 was up-regulated in the tumor tissue compare to the adjacent tissue [39.0％(48/123)].The expression of NOX2 and the relationship of clinical-pathology showed the expression of NOX2 had no correlation with gender,age,differentiation of tumor (X2 value were 0.852,0.150,5.062,P＞0.05).The result of spearman rank correlation showed that the NOX2 was positively correlated with that of VEGF.Conclusion:NOX2 plays an important role in the genesis and development in the gastric cancer,the expression of NOX2 was closely correlated with the VEGF.

Characterization of molecular signature of the roots of Paeonia lactiflora during growth / 中国天然药物

The roots of Paeoniae lactiflora Pall. are widely consumed as crude drugs in Asian countries due to their remarkable beneficial health effects. The present research was undertaken to illuminate the dynamic changes in metabolites and enzymes and facilitate selection of the harvesting time when the herb can provide optimum health benefits. P. lactiflora roots were analyzed at 12 stages of growth for monoterpenoid glycosides, phenols, nucleosides, nucleobases, amino acids, and polysaccharides by high-performance liquid chromatography with photodiode array detector, ultra-high pressure liquid chromatography coupled with tandem mass spectrometry, and UV spectrophotometry. The enzyme activities of plant β-glucosidases and esterases were determined by UV methods. The total content of monoterpenoid glycosides and phenols peaked in December. For nucleosides and nucleobases, the highest content appeared in April. The maximum phasic accumulation of the total amino acids took place in March, and the content of total polysaccharides reached a peak value in September. December, April, and March were selected as the appropriate harvesting times for producing natural medicinal or health food products. Plant β-glucosidases and esterases showed the highest activity in December and May, respectively. When the activity of β-glucosidase increased, esterase activity decreased, while the contents of oxypaeoniflora and paeoniflorin increased. When esterase activity increased, the contents of benzoylpaeoniflorin, paeoniflorin, and gallic acid decreased. In conclusion, the results from the present study would be useful in determination of the suitable time for harvesting P. lactiflora roots for medicinal purposes.

Screening for differentially-expressed proteins in ovary of primary dysmenorrheal mice with Xiangfu Siwu decoction administration using nano LC-LTQ-Orbitrap-MS/MS / 中国中药杂志

To study the mechanism of Xiangfu Siwu decoction in treating primary dysmenorrhea, differentially-expressed proteins in ovary of primary dysmenorrheal mice with Xiangfu Siwu decoction administration were screened based on proteome technology using nano LC-LTQ-Orbitrap-MS/MS. Estradiol benzoate and oxytocin were used to produce dysmenorrheal mice model. The model mice were orally administrated with Xiangfu Siwu decoction for 3 days, and 1 h after the last administration, the ovary samples were collected. After protein denaturation, reduction, alkylation, desalination and enzymatic hydrolysis, identification was carried out by nano LC-LTQ-Orbitrap-MS/MS technology. The obtained data was processed by using Thermo Proteome discoverer 1.4 software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed. The significant differentially-expressed protein was checked using Western blot technology in ovary samples. A total of 106 differentially-expressed proteins were identified during the normal, model and administration group. Most of them participate cellular processes. Adherens junction and focal adhesion pathways play a regulatory role in various cell signaling pathways. Protein ADRM1 was validated. Compared to the normal group, it was up-regulated expression in the model group. After administration, the expression of ADRM1 was down-regulated. Through the comparative analysis, a series of differentially-expressed proteins involved in primary dysmenorrheal mice with Xiangfu Siwu decoction administration were obtained. Protein ADRM1 may become a target for Xiangfu Siwu decoction.

Effects of different penetration enhancers on pharmacokinetics of active components in Xiangfu Siwu transdermal patches / 中国中药杂志

To study the effect of different penetration enhancers on the pharmacokinetic characters of six active components in Xiangfu Siwu transdermal patch (XBW) and optimize the best penetration enhancers. During the experiment, the patches containing different penetration enhancers were stuck on the rat's skin, and then the blood samples were acquired at different time points. Six active components in plasma were determined by UPLC-MS/MS. The main pharmacokinetic parameters were calculated with DAS software package. The total factor scores (F) of the plasma concentrations of six components at every time point in different groups were calculated using principle component analysis, and the areas under F versus time curves (AUCF-t) were employed to be the indexes for selecting penetration enhancers. The results demonstrated that compared with the control group, the AUCF-t from other groups increased prominently and furthermore, 5% menthol manifested the best effect. In this research, 5% menthol could remarkably promote the percutaneous penetration effect of the six active compounds in XBW, and it could provide a scientific basis for the preparation research of XBW.