ABSTRACT
Paeoniae Radix Rubra (PRR) known as Chishao, in China, is the dried root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch, with a history of over 2000â years in traditional Chinese medicine, is employed to clear heat, cool the blood, dispel blood stasis, and alleviate pain. Phytochemical investigations identified 264 compounds that contained monoterpenes and their glycosides, sesquiterpenes, triterpenes, steroids, flavonoids, lignans, tannins, volatile oils, and other compounds. It has been reported to have different pharmacological activities, including cardiovascular-protective, antidepressive, neuroprotective, antitumor, hepatoprotective, and anti-inflammatory effects. This study offers a comprehensive review covering ethnopharmacology, phytochemistry, pharmacological activities, therapeutic mechanism for blood stasis syndrome, and quality control of PRR. The comprehensive analysis aims to achieve a thorough understanding of its effects and serves as a foundation for future research and development.
Subject(s)
Paeonia , Quality Control , Paeonia/chemistry , Humans , Phytochemicals/pharmacology , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Medicine, Chinese Traditional , Ethnopharmacology , Animals , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic useABSTRACT
Two new guaiacene-type sesquiterpenes 13α-dihydroixerin acid, ixerin acid and one new secoguaiacene-type sesquiterpene secoixerin Z, along with four known compounds, were separated from ethanol extract of Ixeris sonchifolia. The structures were determined based on the detailed spectroscopic and physicochemical methods. The cytotoxic activity of the isolates was tested against A549 cells. Among them, compound 3 exhibited potent cytotoxicity against A549 cells with the IC50 of 5.6 ± 0.9 µM.
Subject(s)
Asteraceae , Sesquiterpenes , Lactones/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Asteraceae/chemistry , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
Endometriosis is a common gynecological illness in women of reproductive age that significantly decreases life quality and fertility. Paeonol has been shown to play an important part in endometriosis treatments. Understanding the mechanism is critical for treating endometriosis. In this study, autologous transplantation combined with a 28 day ice water bath was used to create a rat model of endometriosis with cold clotting and blood stagnation. The levels of estradiol and progesterone in plasma were detected by ELISA, and the pathological changes of ectopic endometrial tissue were examined by H&E staining, which proved the efficacy of paeonol. For metabolomic analysis of plasma samples, UPLC-Q/TOF-MS was combined with multivariate statistical analysis to identify the influence of paeonol on small molecule metabolites relevant to endometriosis. Finally, the key targets were screened using a combination of network pharmacology and molecular docking approaches. The results showed that the pathological indexes of rats were improved and returned to normal levels after treatment with paeonol, which was the basis for confirming the efficacy of paeonol. Metabolomics results identified 13 potential biomarkers, and paeonol callbacks 7 of them, involving six metabolic pathways. Finally, four key genes were found for paeonol therapy of endometriosis, and the results of molecular docking revealed a significant interaction between paeonol and the four key genes. This study was successful in establishing a rat model of endometriosis with cold coagulation and blood stagnation. GCH1, RPL8, PKLR, and MAOA were the key targets of paeonol in the treatment of endometriosis. It is also demonstrated that metabolomic techniques give the potential and environment for comprehensively understanding drug onset processes.
Subject(s)
Drugs, Chinese Herbal , Endometriosis , Humans , Rats , Female , Animals , Endometriosis/drug therapy , Molecular Docking Simulation , Metabolomics/methods , Acetophenones/analysis , Drugs, Chinese Herbal/pharmacology , Chromatography, High Pressure Liquid/methodsABSTRACT
Guyinjian (GYJ) is an ancient classic formula of traditional Chinese medicine used for the treatment of liver and kidney yin deficiency; it was derived from the book "Jing Yue Quan Shu" in the Ming Dynasty. Modern clinical observation experiments have shown that GYJ has a definite therapeutic effect on the treatment of gynecological diseases such as kidney deficiency type oligomenorrhea, climacteric syndrome, intermenstrual bleeding, pubertal metrorrhagia, etc. However, the lack of GYJ quality control studies has greatly limited the development of its wider clinical application. In this study, a validated UPLC-MS/MS method was developed successfully for the first time and used to quantify fourteen compounds in GYJ samples with good specificity, linearity (r = 0.9960-0.9999), precision (RSD% ≤ 3.18%), stability (RSD% ≤ 2.22%) and accuracy (recovery test within 88.64-107.43%, RSD% at 2.82-6.22%). Simultaneously, the determination results of 15 batches of GYJ samples were analyzed by multivariate statistical methods, and it was found that the compounds have a greater influence on batch-to-batch stability, mainly Rehmannioside D, Loganin, Morroniside, Ginsenoside Re, and 3',6-Disinapoylsucrose. The proposed new method has the advantages of high sensitivity, high selectivity, and rapid analysis, which provides a reference for the GYJ quality control study.
Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid , Drugs, Chinese Herbal/analysis , Reproducibility of Results , Tandem Mass Spectrometry/methodsABSTRACT
BACKGROUND: Perioperative competence is necessary to evaluate operating room nurses. The Perceived Perioperative Competence Scale-Revised (PPCS-R) is the only available tool developed specifically for the perioperative setting. However, there is a lack of research on the reliability and validity of this scale among Chinese nurses. Thus, the aim of this study is to translate, culturally adapt, and evaluate the psychometric properties of the Perioperative competence Scale-Revised (PPCS-R) among operating room nurses in China. METHODS: Instrument cultural adaptation was carried out through forward translation, back translation, expert panel evaluation and pretesting. The psychometric properties (content validation, item analysis, construct validation, and reliability coefficient) of the Chinese PPCS-R (C-PPCS-R) were examined. An online survey was completed from June to August 2020 by operating room nurses (N = 480) in five third-grade class-A hospitals in Beijing. RESULTS: The item analysis identified six items for scale reduction. Exploratory factor analysis showed the remaining 34 items loaded on six factors, which were named in accordance with the original scale. The six-factor model showed a good fit through confirmatory factor analysis. The item content validity index for the C-PPCS-R items ranged from 0.857 to 1.000, and that for the total scale was 0.875. Cronbach's alpha was showed 0.787. Together, the six factors explained 68.62% of the variance. CONCLUSIONS: The 34-item C-PPCS-R showed good validity and reliability to measure perceived competence among operating room nurses in the Chinese context. The scale can assist nurse managers to identify operating room nurses' perceived competence, and provides evaluation criteria for career planning, performance appraisal, job assignment, and continuing education.
ABSTRACT
Senile plaque accumulation and neurofibrillary tangles are primary characteristics of Alzheimer's disease. We aimed to assess the protective functions of naringenin against ß-amyloid protein fragment 25-35 (Aß25-35)-caused nerve damage in differentiated PC12 cells, and study the potential mechanisms. We evaluated cell viability and apoptosis using the 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test and flow cytometry, respectively. Moreover, we measured protein kinase B (Akt), glycogen synthase kinase-3ß (GSK-3ß), and caspase-3 activity via western blotting and RT-PCR. We found that naringenin protected cell against Aß25-35-caused nerve damage by increasing cell viability, promoting Akt and GSK3ß activation, and inhibiting cell apoptosis and caspase-3 activity. However, treatment with the estrogen receptor (ER) antagonist ICI182, 780 or phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 suppressed the effects of naringenin. Our results suggested that naringenin could effectively suppress Aß25-35-caused nerve damage in PC12 cells by regulating the ER and PI3K/Akt pathways.
Subject(s)
Amyloid beta-Peptides/toxicity , Cytoprotection/physiology , Endoplasmic Reticulum/metabolism , Flavanones/pharmacology , Peptide Fragments/toxicity , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Cell Survival/drug effects , Cell Survival/physiology , Cytoprotection/drug effects , Dose-Response Relationship, Drug , Endoplasmic Reticulum/drug effects , PC12 Cells , Phosphoinositide-3 Kinase Inhibitors , RatsABSTRACT
Four pentasaccharide resin glycosides, acutacoside F-I (1-4), were isolated from the aerial parts of Argyreia acuta. These compounds were characterized as a group of macrolactones of operculinic acid A, and their lactonization site of 11S-hydroxyhexadecanoic acid was esterified at the second saccharide moiety (Rhamnose) at C-2. The absolute configuration of the aglycone was S. Their structures were elucidated by established spectroscopic and chemical methods.
Subject(s)
Glycosides/chemistry , Ipomoea/chemistry , Lactones/chemistry , Oligosaccharides/chemistry , Resins, Plant/chemistry , Glycosides/isolation & purification , Lactones/isolation & purification , Molecular Structure , Oligosaccharides/isolation & purification , Palmitic Acids/chemistry , Plant Components, Aerial/chemistry , Plant Extracts/chemistry , Rhamnose/chemistryABSTRACT
Metabolomics is a powerful new technology that allows the assessment of global low-molecular-weight metabolites in a biological system and which shows great potential in biomarker discovery. Analysis of the key metabolites in body fluids has become an important part of improving the diagnosis, prognosis, and therapy of diseases. Hepatitis C virus (HCV) is a major leading cause of liver disease worldwide and a serious burden on public health. However, the lack of a small-animal model has hampered the analysis of HCV pathogenesis. We hypothesize that an animal model (Tupaia belangeri chinensis) of HCV would produce a unique characterization of metabolic phenotypes. Ultra-performance liquid-chromatography/electrospray ionization-SYNAPT-high-definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) coupled with pattern recognition methods and system analysis was carried out to obtain comprehensive metabolomics profiling and pathways of large biological data sets. Taurine, hypotaurine, ether lipid, glycerophospholipid, arachidonic acid, tryptophan, and primary bile acid metabolism pathways were acutely perturbed, and 38 differential metabolites were identified. More important, five metabolite markers were selected via the "significance analysis for microarrays" method as the most discriminant and interesting biomarkers that were effective for the diagnosis of HCV. Network construction has led to the integration of metabolites associated with the multiple perturbation pathways. Integrated network analysis of the key metabolites yields highly related signaling pathways associated with the differentially expressed proteins, which suggests that the creation of new treatment paradigms targeting and activating these networks in their entirety, rather than single proteins, might be necessary for controlling and treating HCV efficiently.
Subject(s)
Hepacivirus/growth & development , Metabolome , Metabolomics/methods , Tupaia/metabolism , Animals , Chromatography, High Pressure Liquid/methods , Hepacivirus/physiology , Host-Pathogen Interactions , Humans , Male , Metabolic Networks and Pathways , Models, Biological , Multivariate Analysis , Principal Component Analysis , Signal Transduction , Spectrometry, Mass, Electrospray Ionization/methods , Tupaia/virologyABSTRACT
To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.
Subject(s)
Liver Diseases/drug therapy , Metabolome , Proteome/metabolism , Animals , Anthraquinones/pharmacology , Biomarkers/metabolism , Drug Evaluation, Preclinical , Drug Synergism , Drug Therapy, Combination , Drugs, Chinese Herbal/pharmacology , Iridoids/pharmacology , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Medicine, Chinese Traditional , Metabolomics , Molecular Targeted Therapy , Proteomics , Rats , Rats, Wistar , Umbelliferones/pharmacologyABSTRACT
The metabolism of swertiamarin in vivo was studied by LC-MS following 2,4-dinitrophenylhydrazine derivatization. The ionization efficiency of the main metabolite erythrocentaurin was greatly enhanced by the new analytical method developed, and erythrocentaurin was successfully detected for the first time in rat plasma after oral administration of swertiamarin. Methyl 4-formylbenzoate was used as the internal standard to quantify erythrocentaurin in rat plasma in negative mode by UPLC-TOF-MS, and it was found that erythrocentaurin reached the maximum mean plasma concentration of 425.8 ± 127.6 ng/mL at about 2 h after oral administration of swertiamarin at a dose of 200 mg/kg. A metabolic pathway of swertiamarin to erythrocentaurin was proposed. Swertiamarin is first hydrolyzed by bacterial ß-glucusidase to give the aglycone, which is readily converted to erythrocentaurin. The monoterpene compound swertiamarin was found to be metabolized to dihydroisocoumarin and alkaloid compounds in vivo, which may be responsible for the pharmacological effect of swertiamarin. The results may shed light on the clinical efficacy of swertiamarin and the new analytical method may assist in studies for the metabolism of other natural iridoids and secoiridoids in vivo.
Subject(s)
Chromatography, High Pressure Liquid , Iridoid Glucosides/blood , Iridoid Glucosides/metabolism , Pyrones/blood , Pyrones/metabolism , Tandem Mass Spectrometry , Administration, Oral , Animals , Chromatography, High Pressure Liquid/methods , Iridoid Glucosides/administration & dosage , Iridoid Glucosides/analysis , Isocoumarins/analysis , Isocoumarins/blood , Isocoumarins/metabolism , Limit of Detection , Metabolic Networks and Pathways , Phenylhydrazines/chemistry , Pyrones/administration & dosage , Pyrones/analysis , Rats , Rats, Wistar , Swertia/chemistry , Tandem Mass Spectrometry/methodsABSTRACT
Serum pharmacochemistry of traditional Chinese medicine (TCM) is designed to screen the efficacy material base of TCMs from the constituents absorbed into the blood after oral administration. The theory and method is in accordance with the effect characteristics of TCMs, and reflects the interaction between the body and the drugs, has become an effective pathway for researching the efficacy material base of TCMs which has been recognized and used widely. In the paper, the previous research contents and methods of the serum pharmacochemistry of TCM were reviewed, and on the basis of the further validity of the special administration form of the TCM formula and the corresponding property to TCM syndrome, the new strategy of serum pharmacochemistry of TCM integrating the metabonomics technologies was put forward. According to the strategy, we take the biological characters of TCM syndrome as a research starting point, taking TCM formula as object, using the metabolic biomarkers of syndromes or disease to evaluate the therapeutic effect of formula and screen the compounds of TCMs in serum which are highly correlated with the metabolic biomarkers through the correlation analysis, and by further biological validation to finally confirm the efficacy material basis of TCMs. Integrating with the systems biology technologies, the theory and method of serum pharmacochemistry of TCM will further develop, and open a new chapter in the interpretation of the theory of TCM.
Subject(s)
Drugs, Chinese Herbal/chemistry , Serum/chemistry , Animals , Drug Therapy/trends , Drugs, Chinese Herbal/pharmacokinetics , Humans , MetabolomicsABSTRACT
OBJECTIVE: To investigate the causes and affecting factors of unplanned reoperations in cancer patients. METHODS: All patients, who underwent surgery and unplanned surgical reoperations in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between November 1, 2012 and October 1, 2013, were included in this study. The causes and affecting factors of unplanned reoperations were retrospectively analyzed with logistic regression model. RESULTS: A total of 16, 362 operations were performed in that period, in which 126 cases underwent unplanned reoperation. The incidence rate of unplanned reoperation was 0.77%. The top three causes for unplanned reoperation were bleeding or hematoma in 44 cases (34.92%), wound infection or split in 37 cases (29.37%), and anastomotic leak in 14 cases (11.11%). Logistic regression analysis showed that tumor classification, surgery grade and gender were independent factors for the unplanned reoperations. CONCLUSIONS: The main causes of unplanned reoperation are bleeding or hematoma, wound infection or split and anastomotic leak. Tumor classification, surgery grade and gender are the independent factors for unplanned reoperations.
Subject(s)
Postoperative Complications/epidemiology , Reoperation/statistics & numerical data , Anastomotic Leak , Hemorrhage , Humans , Logistic Models , Neoplasms , Retrospective StudiesABSTRACT
Infectious bronchitis virus (IBV) causes infectious bronchitis in chicken, an acute, highly contagious respiratory infection. Because of genetic mutations and recombination, IBV forms many subtypes, which makes it difficult to treat the disease and apply commercial vaccines. Therefore, to detect IBV in time and stop the virus from spreading, a novel and convenient IBV detection technology based on reverse transcription recombinase-aided amplification (RT-RAA) was established in this study. According to the S1 gene of IBV CH I-V and Mass genotypes and S1 gene of IBV CH VI genotype, a set of optimal primers were designed and selected to establish a real-time dual fluorescence RT-RAA method. The lowest detection line was 10 copies/µL of RNA molecules and the method exhibited no cross-reactivity with avian reticuloendotheliosis virus (REV), infectious bursal disease virus (IBDV), avian leukosis virus (ALV), Newcastle disease virus (NDV), chicken infectious anemia virus (CIAV), infectious laryngotracheitis virus (ILTV), Marek's disease virus (MDV), and H9N2 avian influenza virus (H9N2), demonstrating high specificity. When compared to qPCR detection results, our method achieved a sensitivity of 96.67%, a specificity of 90%, and a Kappa value of 0.87 for the IBV CH I-V and Mass genotypes, and achieved a sensitivity of 100%, a specificity of 97.73%, and a Kappa value of 0.91 for the IBV CH VI genotype.
ABSTRACT
Introduction: Danggui Buxue Decoction (DBD) is a clinically proven, effective, classical traditional Chinese medicine (TCM) formula for treating blood deficiency syndrome (BDS). However, its effects and effective constituents in the treatment of BDS remain unclear, limiting precise clinical therapy and quality control. This study aimed to accurately evaluate the effects of DBD and identify its effective constituents and quality markers. Methods: BDS was induced in rats by a combined injection of acetylphenylhydrazine and cyclophosphamide, and the efficacy of DBD against BDS was evaluated based on body weight, body temperature, energy metabolism, general status, visceral indices, histopathology, biochemical markers, and metabolomics. The effects of DBD on urinary and serum biomarkers of BDS were investigated, and the associated metabolic pathways were analyzed via metabolomics. Guided by Chinmedomics, the effective constituents and quality markers of DBD were identified by analyzing the dynamic links between metabolic biomarkers and effective constituents in vivo. Results: DBD improved energy metabolism, restored peripheral blood and serum biochemical indices, and meliorated tissue damage in rats with BDS. Correlation analyses between biochemical indices and biomarkers showed that 15(S)-HPETE, LTB4, and taurine were core biomakers and that arachidonic acid, taurine, and hypotaurine metabolism were core metabolic pathways regulated by DBD. Calycosin-7-glucoside, coumarin, ferulic acid sulfate, cycloastragenol, (Z)-ligustilide + O, astragaloside IV, acetylastragaloside I, and linoleic acid were identified as effective constituents improving the hematopoietic function of the rats in the BDS model. Additionally, calycosin-7-glucoside, ferulic acid, ligustilide, and astragaloside IV were identified as quality markers of DBD. Conclusion: The hematopoietic function of DBD was confirmed through analysis of energy metabolism, biochemical markers, histopathology, and metabolomics. Moreover, by elucidating effective constituents of DBD in BDS treatment, quality markers were confirmed using a Chinmedomics strategy. These results strengthen the quality management of DBD and will facilitate drug innovation.
ABSTRACT
Among broilers, the main pathogen that leads to swollen head syndrome (SHS) is the subgroup C avian metapneumovirus (aMPV-C). The aMPV-C infection can lead to an upsurge in the rate of soft-shell eggs, resulting in reduced egg production and seriously affecting the economy of the livestock industry. Therefore, a rapid method for aMPV-C detection needs to be invented. According to the N gene of aMPV-C, we designed the specific probe and primer and created a reverse transcription recombinase-aided amplification assay (RT-RAA) for the detection of aMPV-C. aMPV-C could be detected quickly and specifically by this method at 41 °C for 30 min. The sensitivity assay inferred that the minimum detection threshold of RT-RAA was 3.38 × 101 copies/µL. A specificity assay showed that the RT-RAA method did not cross-react with other subgroups (aMPV-A, aMPV-B, aMPV-D) or other viruses (H9N2, NDV, IBV, IBDV). Forty samples of known clinical background were tested by RT-RAA and RT-qPCR. The two approaches had a 100% correlation rate. In conclusion, this research successfully created an RT-RAA assay for aMPV-C.
ABSTRACT
Shaofuzhuyu Decoction (SFZYD) is a classical formula for treating endometriosis of cold coagulation and blood stasis (ECB). The clinical efficacy is definite, but the potential mechanisms require further exploration. The study aimed to reveal the metabolic mechanisms of SFZYD for treating ECB using mass spectrum oriented metabolomics. Firstly, the study has used metabolomics data to identify biomarkers and to investigate metabolic pathways. Then, the targets of SFZYD for treating ECB were dug by building and analyzing a biological network of biomarkers. Finally, the obtained targets were validated by molecular docking. This study found that SFZYD could significantly improve the biochemical indicators and metabolic abnormalities of ECB. A total of 18 ECB-related biomarkers in 7 pathways were identified. SFZYD was able to regulate the levels of 14 biomarkers that were involved in 5 metabolic pathways. Furthermore, the study yielded 119 SFZYD active ingredients, 1119 target proteins associated with endometriosis, 610 targets associated with biomarkers, 727 GO functions, and 159 KEGG pathways. Biological network analysis constructed a network diagram of herbs-ingredients-targets-biomarkers, and found 6 key active ingredients and 9 core targets. Molecular docking showed high affinities between key ingredients and core targets. This study elucidated that SFZYD plays a role in treating ECB through multi-component, multi-target, and multi-pathway.
ABSTRACT
Scoparone is an important constituent of Yinchenhao (Artemisia annua L.), a famous medicinal plant, and displayed bright prospects in the prevention and therapy of liver injury. However, the precise molecular mechanism of hepatoprotective effects has not been comprehensively explored. Here, metabolomics techniques are the comprehensive assessment of endogenous metabolites in a biological system and may provide additional insight into the mechanisms. The present investigation was designed to assess the effects and possible mechanisms of scoparone against carbon tetrachloride-induced liver injury. Ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) combined with pattern recognition approaches including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were integrated to discover differentiating metabolites. Results indicate five ions in the positive mode as differentiating metabolites. Functional pathway analysis revealed that the alterations in these metabolites were associated with primary bile acid biosynthesis, pyrimidine metabolism. Of note, scoparone has a potential pharmacological effect through regulating multiple perturbed pathways to the normal state. Our findings also showed that the robust metabolomics techniques are promising for getting biomarkers and clarifying mechanisms of disease, highlighting insights into drug discovery.
Subject(s)
Coumarins/pharmacology , Cytoprotection/drug effects , Liver/drug effects , Liver/metabolism , Metabolomics/methods , Spectrometry, Mass, Electrospray Ionization , Animals , Biomarkers/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Chromatography, High Pressure Liquid , Rats , Rats, WistarABSTRACT
To discover and screen the constituents or metabolites absorbed into blood after oral administration of herbal medicines tends to be more and more difficult. In this work, an integrative pattern recognition approach of principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) was successfully applied for rapid discovery of natural compounds from herbal medicines. A rapid, sensitive, and reliable ultra performance liquid chromatography coupled with electrospray ionization/quadrupole-time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS) method with Masslynx™ software was established to characterize the chemical constituents and rats metabolites of Phellodendri amurensis cortex (Guan Huangbai, GHB). The analysis was performed on a Waters UPLC HSS T3 column (2.1 × 100 mm, 1.8 µm) using gradient elution system. A hyphenated electrospray ionization and quadrupole-time-of-flight analyzer was used for the determination of accurate mass of the protonated or deprotonated molecule and fragment ion in both negative and positive modes. A total of 46 peaks were obtained, 41 of which were tentatively characterized from GHB. In the S-plot of OPLS-DA, 24 interested ions (17 ions in positive mode and 6 ions in negative mode) were extracted, among them, 12 absorbed prototype components of GHB and 12 metabolites were identified in vivo. Major metabolic reactions of GHB were demethylation, methylation and glucuronidation. This is the first report on systematic analysis of chemical constituents and in vivo metabolites of GHB. It is concluded that UPLC-MS coupled with pattern recognition approach for the identification of herbal constituents in biological samples has been successfully developed. The method can also be applied to rapid discovery and global characterization of the constituents in rat serum after oral administration of other herbal medicines.
Subject(s)
Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/metabolism , Pattern Recognition, Automated/methods , Spectrometry, Mass, Electrospray Ionization/methods , Animals , Male , Multivariate Analysis , Rats , Rats, Sprague-DawleyABSTRACT
Shaoyao-Gancao decoction (SGD), a traditional Chinese formulae containing Paeoniae Radix and Glycyrrhizae Radix, is commonly used to relieve abdominal pain. It has attracted increasingly much attention as one of the most popular and valuable herbal medicine in clinic. However, the systematic analysis of chemical constituents of SGD are difficult to determine and thus remain unclear. In this paper, a rapid, sensitive, and reliable ultra-performance LC-ESI/quadrupole-TOF high-definition MS (UPLC-ESI-Q-TOF-MS) with automated MetaboLynx analysis in negative ion mode were established to characterize the chemical constituents of SGD. The analysis was performed on a Waters UPLC(TM) HSS T3 (2.1 × 100 mm, 1.8 µm) using gradient elution system. MS/MS fragmentation behavior was proposed for aiding the structural identification of the components. With the optimized conditions, a total of 58 peaks were tentatively characterized by comparing the retention time and mass spectrometry data and retrieving the reference literatures. Of note, 44 ingredients were identified from Glycyrrhizae Radix, and 14 were from Paeoniae Radix. It is concluded that a rapid and robust platform based on UPLC-ESI-Q-TOF-MS was successfully developed for globally identifying multiple-constituent of traditional Chinese medicine prescriptions. This is the first report on systematic analysis of chemical constituents and in vivo metabolites of SGD.
Subject(s)
Drugs, Chinese Herbal/analysis , Paeonia/chemistry , Drugs, Chinese Herbal/chemistry , Mass Spectrometry , Molecular Structure , Time FactorsABSTRACT
This study aimed to investigate the in vivo behaviors of the main components in traditional Chinese medicine (TCM) fomulae. The plasma pharmacokinetics, tissue distribution and excretion of the main component-schisandrin in rats after oral administration of a classical TCM prescription, shengmaisan (SMS), were studied by a developed and validated UPLC-MS/MS method. The separation of schisandrin was achieved on a UPLC HSS T3 column with a mobile phase consisting of acetonitrile and water at a flow rate of 0.5 mL/min by linear gradient elution. The MS/MS detection was carried out by monitoring the fragmentation of m/z 415.22 â 384.26 for schisandrin on a triple quadrupole mass spectrometer. The result showed that the method was suitable for the quantification of schisandrin in plasma, tissue and excreta samples with satisfactory selectivity, precision, accuracy, sensitivity, linearity and recovery. Pharmacokinetic results showed a rapid absorption phase with the mean Tmax of 0.17 h and a relatively slow elimination proceeding with a half-life (T1/2 ) of 5.24 ± 1.28 h. The tissue distribution showed the maximum concentration distributions of schisandrin after oral administration of SMS were in the order of small intestine > large intestine > lung > liver > kidney > spleen > heart > brain. Only 0.005-0.006% of schisandrin was recovered in feces and was not detected in urine.