Determination and Mechanism Prediction of Potential Active Ingredients in Erdongtang Based on UHPLC-QqQ-MS and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo establish an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry（UHPLC-QqQ-MS） for determination of the active ingredients in Erdongtang， and to predict the targets and pathways of anti-insulin resistance action of this formula. MethodThe analysis was performed on an ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-3 min， 90%-87%A； 3-6 min， 87%-86%A； 6-9 min， 86%-83%A； 9-11 min， 83%-75%A； 11-18 min， 75%-70%A； 18-19 min， 70%-52%A； 19-22 min， 52%A； 22-25 min， 52%-5%A； 25-27 min， 5%-90%A； 27-30 min， 90%A）. The contents of active ingredients in Erdongtang was detected by electrospray ionization（ESI） and multiple reaction monitoring（MRM） mode under positive and negative ion modes. On this basis， network pharmacology was applied to predict the targets and pathways of Erdongtang exerting anti-insulin resistance effect. ResultThe 20 active ingredients in Erdongtang showed good linear relationships within a certain mass concentration range， and the precision， stability， repeatability and recovery rate were good. The results of determination showed that the ingredients with high content in 15 batches of samples were baicalein（1 259.39-1 635.78 mg·L-1）， baicalin（1 078.37-1 411.52 mg·L-1）， the ingredients with medium content were mangiferin（148.59-217.04 mg·L-1）， timosaponin BⅡ（245.10-604.89 mg·L-1）， quercetin-3-O-glucuronide（89.30-423.26 mg·L-1）， rutin（46.91-1 553.61 mg·L-1）， glycyrrhizic acid（55.97-391.47 mg·L-1）， neomangiferin（37.45-127.03 mg·L-1）， nuciferine（0.89-63.48 mg·L-1）， hyperoside（6.96-136.78 mg·L-1）， liquiritin（30.89-122.78 mg·L-1）， liquiritigenin（26.64-110.67 mg·L-1）， protodioscin（58.57-284.26 mg·L-1）， the ingredients with low content were wogonin（7.16-20.74 mg·L-1）， pseudoprotodioscin（5.49-22.96 mg·L-1）， ginsenoside Rb1（7.31-23.87 mg·L-1）， ginsenoside Rg1（10.78-28.33 mg·L-1）， ginsenoside Re（7.78-24.76 mg·L-1）， ophiopogonin D（2.08-4.29 mg·L-1）， methylophiopogonanone A（0.74-1.67 mg·L-1）. The results of network pharmacology indicated that the mechanism of anti-insulin resistance exerted by Erdongtang might be related to the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway. ConclusionThe established UHPLC-QqQ-MS has the advantages of simple sample processing， strong exclusivity and high sensitivity， and can simultaneously determine the contents of the main ingredients from seven herbs in Erdongtang， which can lay the foundation for the development of Erdongtang compound preparations. The results of the network pharmacology can provide a reference for the mechanism study of Erdongtang in the treatment of type 2 diabetes mellitus.

Hepatic metabolomics combined with network pharmacology to reveal the correlation between the anti-depression effect and nourishing blood effect of Angelicae Sinensis Radix / 中国天然药物

Angelicae Sinensis Radix (AS) is reproted to exert anti-depression effect (ADE) and nourishing blood effect (NBE) in a rat model of depression. The correlation between the two therapeutic effects and its underlying mechanisms deserves further study. The current study is designed to explore the underlying mechanisms of correlation between the ADE and NBE of AS based on hepatic metabonomics, network pharmacology and molecular docking. According to metabolomics analysis, 30 metabolites involved in 11 metabolic pathways were identified as the potential metabolites for depression. Furthermore, principal component analysis and correlation analysis showed that glutathione, sphinganine, and ornithine were related to pharmacodynamics indicators including behavioral indicators and hematological indicators, indicating that metabolic pathways such as sphingolipid metabolism were involved in the ADE and NBE of AS. Then, a target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis, where a total of 107 pathways were collected. Moreover, 37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer (UPLC-Triple-TOF/MS) in AS extract that passed the filtering criteria were used for network pharmacology, where 46 targets were associated with the ADE and NBE of AS. Pathway enrichment analysis further indicated the involvement of sphingolipid metabolism in the ADE and NBE of AS. Molecular docking analysis indciated that E-ligustilide in AS extract exhibited strong binding activity with target proteins (PIK3CA and PIK3CD) in sphingolipid metabolism. Further analysis by Western blot verified that AS regulated the expression of PIK3CA and PIK3CD on sphingolipid metabolism. Our results demonstrated that sphingolipid metabolic pathway was the core mechanism of the correlation between the ADE and NBE of AS.

Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase / 药物分析学报

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after long-term use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saiko-saponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-KB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to sai-kogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosa-ponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

Analysis on Sugar Spectrum Difference Between Wild-simulated and Transplanted Astragali Radix / 中国实验方剂学杂志

ObjectiveTo establish the characteristic sugar spectrum of polysaccharides， oligosaccharides and monosaccharides of wild-simulated and transplanted Astragali Radix， and find out the difference of the sugar spectrum between the two， so as to provide a basis for quality evaluation of Astragali Radix. MethodThe relative molecular weight distribution of polysaccharides from 18 batches of wild-simulated Astragali Radix and 12 batches of transplanted Astragali Radix were characterized by high performance liquid chromatography-evaporative light scattering detection（HPLC-ELSD） to establish the characteristic chromatograms of two kinds of polysaccharides. The difference in the peak area ratio of APS-Ⅱ， a polysaccharide component with a relative molecular weight of 10 kDa， in two kinds of Astragali Radix was analyzed， and the critical value of peak area ratio of APS-Ⅱ was determined by receiver operating characteristic（ROC） curve. At the same time， APS-Ⅱ was partially acid-hydrolyzed by trifluoroacetic acid（TFA） to establish characteristic spectra of two kinds of oligosaccharides from Astragali Radix based on HPLC-ELSD， and the characteristics of differential oligosaccharides were found by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Two kinds of APS-Ⅱ were completely acid-hydrolyzed by TFA and derivatized to establish characteristic spectra of two kinds of monosaccharides from Astragali Radix based on HPLC， PCA and OPLS-DA were performed on the peak area ratio of two kinds of monosaccharides to explore the differences in the composition of two kinds of APS-Ⅱ monosaccharides. ResultThe characteristic sugar spectrum of polysaccharides from Astragali Radix showed that the peak area ratio of APS-Ⅱ was the main difference， and the peak area of APS-Ⅱ of wild-simulated and transplanted Astragali Radix were 89.17%-97.17% and 80.14%-91.96%， respectively. The ROC curve determined the critical value of 92.28% for the difference of APS-Ⅱ peak area ratio of the two kinds of Astragali Radix. The multivariate analysis of APS-Ⅱ oligosaccharides revealed that the peak area ratio of oligosaccharides with polymerization degree≥10 was the main difference， which ranged from 11.835%-19.092% for wild-simulated products and 2.778%-7.017% for transplanted products. The results of monosaccharide characteristic sugar spectrum analysis showed that both Astragali Radix species consisted of six monosaccharides， and glucose and arabinose were the differential monosaccharide fractions. The peak area ratios of glucose and arabinose in wild-simulated products were 85%-93.9% and 2.7%-5.8%， respectively， while those of transplanted products were 74.3%-87.3% and 5.3%-10.7%， suggesting that the structures of the two polysaccharide fractions APS-Ⅱ of Astragali Radix may be different. ConclusionThe difference of sugar spectrum between two kinds of Astragali Radix may be related to the content and structure of APS-Ⅱ， and this study may provide a reference for the study of carbohydrates in Astragali Radix and the quality evaluation of medicinal materials.

Rapid quantitative analysis of 12 chemical constituents in wild-simulated and cultivated Astragali Radix based on UHPLC-MS / 中草药·英文版

Objective: Astragali Radix (AR) is one of the most widely used traditional Chinese medicines (TCMs) for tonic, which can be divided into wild-simulated and cultivated AR according to its cultivation method. However, whether cultivated AR can replace wild-simulated AR has always been a concern. Methods: In this study, a rapid, highly sensitive and specific analytical method using ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS) was developed to quantitatively measure 12 chemical constituents of AR in the different cultivation methods. Results: AR samples were analyzed with a good linear regression relationship (R

Comparative pharmacokinetics of six major compounds in normal and insomnia rats after oral administration of Ziziphi Spinosae Semen aqueous extract / 药物分析学报

Ziziphi Spinosae Semen (ZSS), a traditional Chinese medicine, is used in clinics for the treatment ofinsomnia in China and other Asian countries. Herein, we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control (NC) and para-chlor-ophenylalanine (PCPA)-induced insomnia model (IM) rats that were orally administered the aqueous extract of ZSS. An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass (UHPLC-Q-Orbitrap-MS) method was developed and validated for the simultaneous determination of coclaurine, magnoflorine, spinosin, 6'''-feruloylspinosin, jujuboside A (JuA), and jujuboside B (JuB) in ZSS in rat plasma. The established approach was successfully applied to a comparative pharmacokinetic study. The systemic exposures of spinosin and 6'''-feruloylspinosin were decreased in the IM group compared to the NC group, while plasma clearance (CL) was significantly increased. The Tmax values of JuA and JuB in IM rats were significantly lower than those in NC rats. The T1/2 of JuA in the IM group was significantly accelerated. The pharmacokinetic parameters of coclaurine and magnoflorine were not evidently affected between the two groups. These results indicate that the pathological state of insomnia altered the plasma pharmacokinetics of spinosin, 6'''-feruloylspinosin, JuA, and JuB in the ZSS aqueous extract, providing an experimental basis for the role of ZSS in insomnia treatment. The comparative pharmacokinetics-based UHPLC-Q-Orbitrap-MS using full-scan mode can therefore provide a reliable and suitable means for the screening of potentially effective substances applied as quality markers of ZSS.

Mental health status of patients with coronavirus disease 2019 in Changsha / 中南大学学报(医学版)

OBJECTIVES@#The epidemic of coronavirus disease 2019 (COVID-19) brought psychological stress to the public, especially to patients. This study aims to investigate the mental health of patients with COVID-19 in Changsha.@*METHODS@#We took cross-section investigation for the mental health of 112 patients with COVID-19 via questionnaires. Mann-Whitney test, Chi-square test, and Fisher's exact test were performed to compare general and clinical data between the slight-ordinary patients and severe patients. Single sample -tests were used to compare the difference between the factor scores of the Symptom Check-List 90 (SCL-90) in COVID-19 patients with the norm of 2015 and factor scores of SCL-90 in patients with the severe acute respiratory syndrome (SARS).@*RESULTS@#The obsessive-compulsive, depression, sleep and eating disorders had the highest frequency among the positive symptoms of SCL-90 in patients with COVID-19 in Changsha. The factor scores of somatization, depression, anxiety, phobia anxiety, sleep and eating disorders in patients with COVID-19 were higher than those of the norm (≤0.001 or 0.05).@*CONCLUSIONS@#The levels of somatization, depression, anxiety, phobia anxiety, sleep and eating disorders in patients with COVID-19 in Changsha are higher than those of the norm. However, the mental health of slight-ordinary patients with COVID-19 is better than that of patients with SARS. It needs to provide targeting psychological interventions depending on the severity of patients.

Dynamic metabolic profile changes in urine from D-galactose induced aging rats based: 1H-NMR metabonomics analysis / 中国药理学与毒理学杂志

OBJECTIVE To investigate the dynamic changes in urine metabolic profiles in rats induced by D-galactose (D-Gal),and to study the correlations between the differential metabolites and behavior indicators using the proton nuclear magnetic resonance (1H-NMR)-based metabonomics.METHODS Subcutaneous injection of D-Gal 100 mg· kg-1 for 10 weeks was adopted in the model group.The sample of urine was collected at day 0 (dO),d14,d28,d42,d56 and d70.NMR metabonomics technique was used for acquisition of data,which was analyzed by multivariate statistical analysis.The ability of learning and memory were measured by Morris water maze test from d70.After the behavioral test,the rats were sacrificed and the hippocampus was observed by hematoxylin-eosin staining.RESULTS Principal component analysis (PCA) results revealed that there was considerable difference between the model group and the normal control group at d70.According to the varible importance plot (VIP) calculation and S-plot scores,a total of 12 metabolites were screened and identified as potential biomarkers at d70.The differences of metabolites and Morris water maze test were subjected to correlation analysis,and the results showed that the levels of choline,lactate and dimethylglycine in the model group were significantly increased and negatively correlated with the times of crossing the platform (r =-0.90,-0.50 and-0.52;n=10).Formate was significantly negatively correlated with the time spent in the target area (r =-0.51,n=10),but choline and formate were significantly positively correlated with the escape latency (r =0.72 and 0.53;n=10).However,the levels of creatine and taurine decreased in the model group,which was significantly positively correlated to the times of acrossing platforms (r =0.89 and 0.71;n=10),while alanine was significantly positively correlated to the time spent in the target area(r =0.74,n=10).Taurine,alanine and creatine were significantly negatively correlated with the escape latency (r =-0.66,-0.50 and-0.85;n=10).The correlations between the differential metabolites and the behavioral indicators were further proved.CONCLUSION The metabolic profile changes in urine from D-Gal induced aging model rats are significantly correlated with impairement of ability in learning and memory.1H-NMR metabonomics in urinary metabolic profile changes may be used as an evaluation index in the D-Gal induced aging rats model.

Research advances in psychological suboptimal health / 中国药理学与毒理学杂志

Psychological suboptimal health status is an intermediate state between mental health and mental disease.Without timely intervention,psychological suboptimal health may develop into serious diseases that pose a threat to human physical and mental health,such as depression,anxiety disorders and high blood pressure.This review summarizes the scientific concepts,diagnostic Criteria,intervention and pharmacological research of psychological suboptimal health from the perspective of both modern medicine and traditional Chinese medicine and proposes possible solutions to existing problems in order to contribute to the identification,diagnosis,prevention and treatment of psychological suboptimal health.

Aging and aging related neurodegenerative disease models and drug screening based on Caenorhabditis elegans:research progress / 中国药理学与毒理学杂志

Caenorhabditis elegans is a very important model organism in life sciences. C. elegans has been widely used in research on life sciences, especially in drug screening and the mechanism of drugs, thanks to some of their prominent characteristics, including a short life,short generation cycle, and easy culture and observation. Aging is a complex process, which is the result of multiple factors. There are mainly three types of anti-aging signal pathways in C. elegans, including insulin-insulin-like growth factor-1 signal pathway, diet-restricted signaling pathway and mitochondrial respiratory chain/ATP synthesis pathway. In this paper, we reviewed the aging models based on the above three signaling pathways and the progress in anti-aging drugs based on the above aging models. In addition, a number of C. elegans models of aging-related neurodegenerative diseases can be obtained by using transgenic or chemical mutagenesis. Thus, this paper reviewed the transgenic models of C. elegans associated with neurodegenerative diseases, including theα-synuclein transgenic model of Parkinson disease, theβ-amyloid deposition model of Alzheimer disease, and the polyQ of Huntington disease, and summa?rized the effective drugs based on the above disease models. This review will provide reference for the study of C. elegans in the future screening of anti-aging drugs and drug screening for the prevention and treatment of neurodegenerative diseases.

Metabolomics of ethyl acetate extract from Huangqi Injection on leucopenia mice / 中成药

AIM To investigate the effects of ethyl acetate extract from Huangqi Injection (HQIEACE) on leucopenia mice.METHODS An experimental mouse model of leucopenia was induced by cyclophosphamide.NMR based metabolomic profiling technique coupled with multivariate statistical method was used for performing metabolomic analysis.RESULTS HQIEACE could elevate the levels of white blood cell,monocytes,neutrophils and lymphocyte in modeled mice.The levels of ten potential endogenous metabolites (lipid,leucine,3-D-hydroxybutyrate,lactate,alanine,pyruvate,creatine,scyllo-inositol,betaine and glucose) were reversed.CONCLUSION The metabolic pathways related to the pharmacological effects of HQIEACE on leucopenia are probably involved in body energy metabolism,amino acid metabolism,oxidative stress and choline metabolism.

Urinary metabolomics study of the effects of Scutellaria baicalensis Georgi ethanol extract on D-galactose-induced rats / 药学学报

The purpose of this study is to evaluate the anti-aging effects and reveal the underlying mechanism of Scutellaria baicalensis Georgi ethanol extract (SBG) in D-galactose-induced rats. Fifty rats were randomly divided into five groups: vehicle control group, D-galactose group, and D-galactose combined with 50, 100, 200 mg x kg(-1) SBG. A rat aging model was induced by injecting subcutaneously D-galactose (100 mg x kg(-1)) for ten weeks. At the tenth week, the locomotor activity (in open-field test) and the learning and memory abilities (in Morris water maze test) were examined respectively. The urine was collected using metabolic cages and analyzed by high-resolution 1H NMR spectroscopy combined with multivariate statistical analyses. The SBG at doses of 50, 100 and 200 mg x kg(-1) treatments groups could significantly ameliorate aging process in rats' cognitive performance. The 50, 100, 200 mg x kg(-1) SBG regulated citrate, pyruvate, lactate, trimethylamine (TMA), pantothenate, β-hydroxybutyrate in urine favorably toward the control group. These biochemical changes are related to the disturbance in energy metabolism, glycometabolism and microbiome metabolism, which is helpful to further understanding the D-galactose induced aging rats and the therapeutic mechanism of SBG.

Analysis of AIDS Vaccine Patent Applied in America / 中国药房

OBJECTIVE:To provide reference for AIDS vaccine R&D in China through investigating AIDS vaccine patent ap-proval in America. METHODS:By combining keywords as HIV vaccine(s),AIDS vaccine(s) and Vaccine of HIV(AIDS) and classification number as A61K,A61P and C12P,related patents were retrieved from Thomson Innovation platform during Jan. 1981-Mar. 2015,and then analyzed in respects of patent data,patent approval trend,R&D ability,patent technology field distribu-tion,etc. RESULTS:A total of 1 272 patents were retrieved,including 405 valid patents. From 1985 to 2014,there were three stages for the change of AIDS vaccine application quantity,which were slow rise,fast rise and slow decline period;on the whole, the trend was on the rise. The main players were Duke University,United States Department of Health and Human Services,Pas-teur Institute,Connaught Laboratories Limited and Merck Group. AIDS vaccine R&D focused on pharmaceutical preparation,thera-peutic activity of medicinal preparations,microorganism,enzyme,etc. American scientific research institutions focused more on pharmaceutical preparation and peptide study. CONCLUSIONS:Though the AIDS vaccine field develops slowly,the future is still promising. In this field,America has stronger patent advantage and scientific research strength. AIDS vaccine R&D concentrates on pharmaceutical preparation,therapeutic activity of medicinal preparations and composition.

Clinical value of MGFA classification and QMG score on predicting late extubation after thymectomy in patients with myasthenia gravis / 临床麻醉学杂志

Objective To evaluate clinical value of MGFA classification and QMG score on pre-dicting late extubation after thymectomy for myasthenia gravis(MG).Methods Total of 61 patients with MG received extended thymectomy from January 2007 to February 2012 were enrolled.Patients were divided into two groups:normal extubation group contained the other 47 patients without pro-longed postoperative mechanical ventilation and delayed extubation group included 14 patients with prolonged postoperative mechanical ventilation.The following factors were evaluated:gender,age, weight,MGFA classification,QMG score,history of steroid hormones or anticholinesterase drugs be-fore operation,the function of liver and kidney before operation,preoperative electrolyte,preoperative hemoglobin content,etc.Receiver operator characteristic curve (ROC)was plotted,and the predictive value, sensitivity and specificity of preoperative MGFA clinical classification and QMG score predicting postoperative ventilation in MG were calculated.Results Fourteen patients(22.95%)de-veloped breathing support after the anaesthetic or endotracheal intubation again in 48 hours.the area under ROC curve(AUC)for preoperative MGFA clinical classification predicting postoperative ventila-tion was 0.723 in MG,it had the sensitivity of 78.5% and specificity of 63.8%.The AUC for QMG score predicting postoperative ventilation was 0.866,the QMG score threshold value of 8.5 had the sensitivity of 78.6% and specificity of 87.2%.Conclusion MGFA classification and QMG score can predict late extubation after thymectomy in patients with myasthenia gravis.

Discrimination of patients with Xiao-Chaihu Tang syndrome using 1H NMR metabonomics and partial least square analysis / 药学学报

1H NMR metabonomics approach was used to reveal the chemical difference of urine between patients with Xiao-Chaihu Tang syndrome (XCHTS) and healthy participants (HP). The partial least square method was used to establish a model to distinguish the patients with Xiao-Chaihu-Tang syndrome from the healthy controls. Thirty-four endogenous metabolites were identified in the 1H NMR spectrum, and orthogonal partial least squares discriminant analysis showed the urine of patients with Xiao-Chaihu Tang syndrome and healthy participants could be separated clearly. It is indicated that the metabolic profiling of patients with Xiao-Chaihu Tang syndrome was changed obviously. Fifteen metabolites were found by S-pot of OPLS-DA and VIP value. The contents of leucine, formic acid, glycine, hippuric acid and uracil increased in the urine of patients, while threonine, 2-hydroxyisobutyrate, acetamide, 2-oxoglutarate, citric acid, dimethylamine, malonic acid, betaine, trimethylamine oxide, phenylacetyl glycine, and uridine decreased. These metabolites involve the intestinal microbial balance, energy metabolism and amino acid metabolism pathways, which is related with the major symptom of Xiao-Chaihu Tang syndrome. The patients with Xiao-Chaihu Tang syndrome could be identified and predicted correctly using the established partial least squares model. This study could be served as the basis for the accurate diagnostic and reasonable administration of Xiao-Chaihu-Tang syndrome.

Metabolomics study of doxorubicin induced hepatotoxicity / 药学学报

To reveal the underlying mechanism of doxorubicin induced hepatotoxicity, an NMR-based metabolomic approach combined with multivariate statistical analysis was used to observe its metabolic alternations of rat liver. Sixteen differential metabolites between model rats and normal rats were characterized as potential pathological biomarkers related to doxorubicin induced hepatotoxicity. Six pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, and tyrosine metabolism were regarded as the targeted metabolic pathways according to Metabolic Pathway Analysis (MetPA). The results suggested that the metabolic perturbations in rats with doxorubicin induced hepatotoxicity were mainly involved in amino acid metabolism, lipid pathways, purine metabolism, energy metabolism, dysfunction of biotransformation and oxidative stress. The investigation revealed the effects of doxorubicin on liver in a holistic metabolic way, which laid a foundation for further studies on its toxicity mechanism.

Chemical comparison of different Farfarae Flos by NMR-based metabolomic approaches / 药学学报

1H NMR-based metabolomic approach combined with multivariate statistical analysis was used to evaluate the quality of 21 Farfarae Flos (FF) samples from different growth regions. Principal component analysis showed that wild and cultivated FF could be separated clearly, suggesting a big chemical difference existed between them. Supervised PLS-DA analysis indicated that the wild samples showed higher levels of secondary metabolites, such as bauer-7-ene-3β, 16α-diol, chlorogenic acid, rutin, 7-(3'-ethylcrotonoyloxy)-1α-(2'-methyl-butyryloxy)-3, 14-dehydro-Z-notonipetranone (EMDNT), tussilagone, β-sitosterol and sitosterone. This is consistent with traditional experience that the quality of wild samples are better than that of cultivated ones. The content of pyrrolizidine alkaloids senkirkine also differed greatly among samples from different habitats. The Pearson correlation analysis showed that senkirkine is positively correlated with 4, 5-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 3,4-O-dicaffeoylquinic acid, rutin, kampferol analogues, to a statistically significant extent. The correlation between the toxic compounds and the bioactive components in FF should be further studied.

Comparison between Astragalus membranaceus var. mongholicus and Hedysarum polybotrys based on ITS sequences and metabolomics / 药学学报

Astragalus membranaceus var. mongholicus and Hedysarum polybotrys belong to different genera, but have similar drug efficacy in traditional Chinese medicine theory, and H. polybotrys was used as the legal A. membranaceus var. mongholicus previously. In this study, similarities and differences between them were analyzed via their ITS/ITS2 fragments information. The ITS (internal transcribed spacer) regions were amplified using polymerase chain reaction and then sequenced in two-way. The alignment lengths of ITS regions were 616 bp, in which 508 loci were consistent, and 103 loci were different, accounting for 82.47% and 16.72% of the total ITS nucleotides in length, respectively. As genotype determines phenotype, 1HNMR-based metabolomic approach was further used to reveal the chemical similarities and differences between them. Thirty-four metabolites were identified in the 1H NMR spectra, and twenty-seven metabolites were the common components. Amino acids, carbohydrates and other primary metabolites were similar, while a large difference existed in the flavonoids and astragalosides. This study suggests that A. membranaceus var. mongholicus and H. polybotrys show similarities and differences from molecular and chemical perspectives, which has laid a foundation for elucidating the effective material basis of drug with similar efficacy and resources utilization.

An exploration in the action targets for antidepressant bioactive components of Xiaoyaosan based on network pharmacology / 药学学报

The present study aims to predict the action targets of antidepressant active ingredients of Xiaoyaosan to understand the "multi-components, multi-targets and multi-pathways" mechanism. Using network pharmacology, the reported antidepressant active ingredients in Xiaoyaosan (saikosaponin A, saikosaponin C, saikosaponin D, ferulic acid, Z-ligustilide, atractylenolide I, atractylenolide II, atractylenolide III, paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid and pachymic acid), were used to predict the targets of main active ingredients of Xiaoyaosan according to reversed pharmacophore matching method. The prediction was made via screening of the antidepressive drug targets approved by FDA in the DrugBank database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. The Cytoscape software was used to construct the Xiaoyaosan ingredients-targets-pathways network. The network analysis indicates that the active ingredients in Xiaoyaosan involve 25 targets in the energy metabolism-immune-signal transmutation relevant biological processes. The antidepressant effect of Xiaoyaosan reflects the features of traditional Chinese medicine in multi-components, multi-targets and multi-pathways. This research provides a scientific basis for elucidation of the antidepressant pharmacological mechanism of Xiaoyaosan.

Spectrum-Effect Relationship of Ethyl acetate Fraction in Ethanol Extract fromXiaoyaosan(XYE-E) for Antidepressant Effect Based on1H-NMR / 世界科学技术-中医药现代化

Thearticle is aimed to find the correlation between bioactive components of XYE-E and the antidepressant efficacy, by analyzing the immovability time in tail suspension test (TST) and forced swimming test (FST). Using the method of gray relational analysis, correlation analysis and regression analysis, relating the peak area of each common peak of1H-NMR spectra with the immovability time in TST or FST, we found that there were total 14 chemical components identified in the1H-NMR spectrum of XYE-E. Among them, 8 compounds, including saikosaponin a, saikosaponin c, saikosaponin E, saikosaponin F, saikosaponin G, saikosaponin b2, atractylenolide I and atractylenolide II, had significant correlation with antidepressant efficacy.