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A liquid chromatograph/mass spectrometry (LC/MS) method was developed for the simultaneous quantitation of seven compounds (safflor yellow A, puerarin, daidzein, ginsenosides (Rg(1), Rb(1), Rd), and notoginsenoside R(1)) in rat plasma samples with sufficient sensitivity to facilitate analysis of samples collected after an intravenous injection of Naodesheng. The plasma samples were subjected to protein precipitation with acetone, and analyzed using negative atmospheric pressure chemical ionization mass spectrometry in selected ion monitoring (SIM) mode with baicalin as an internal standard. Good linearity for all the seven compounds was observed. The intra- and inter-day precision of analysis was <15.0% for each compound, and the accuracy ranged from 90.0% to 109.0%. This quantitation method was successfully applied to a pharmacokinetic study of following intravenous injection of rats with Naodesheng.

Agarwood is a resinous, fragrant wood produced by tropical tree species of the genus Aquilaria, and is highly valued for its wide range of uses in medicine, incense, and perfume. In this study, the quality of agarwood and patterns of chemical constituents induced in natural and artificial agarwood by physical injury, chemical inducer, and chemical plus fungal infection were compared using static headspace sampling gas chromatography – mass spectrometry (SHS-GC-MS). The optimal agarwood heating temperature was determined to be 180 °C. The fingerprints of 40 batches of agarwood were established. Multivariate statistical analysis was utilized to identify 15 common and ten differentiating components, respectively. Agarwood induced by the physical method was more similar to natural agarwood. Exploration of the pyrolysis products of chromone derivatives and sesquiterpenes was undertaken to discover the causes of differences in chemical compositions between artificial and natural agarwood. Our findings revealed that benzylacetone, baimuxinal, and guaiol were significant for agarwood incense and these compounds may be used as markers for classification. [ABSTRACT FROM AUTHOR]

Background: Radix Bupleuri-Radix Paeoniae Alba (CH-BS) is a common clinical herb pair, which is often used to treat depression. However, there is little known about the difference in serum chemical profile before and after the compatibility of Radix Bupleuri (CH) and Radix Paeoniae Alba (BS). Objectives: Here, an effective strategy has been developed for screening differences of constituents in vivo before and after compatibility by integrating background subtraction and metabolomics technology. Materials and Methods: First, to obtain the chemical composition from the CH in vivo before compatibility, the Liquid chromatography/Mass spectrometry (LC/MS) data of serum samples in the control group were subtracted from serum samples in the CH group based on the background subtraction method. Moreover, the chemical composition from the CH in vivo after compatibility was obtained by subtracting the LC/MS data of serum samples in the BS group from serum samples in the CH-BS compatibility group. Finally, the difference in the chemical composition from the CH in vivo before and after compatibility was screened and analyzed by metabolomics. Meanwhile, the difference in chemical composition from the BS in vivo before and after the compatibility was found according to the same thought with BS. Results: The results showed that three prototype components were significantly decreased and seven metabolites were significantly increased in CH after compatibility. And eight prototype components and six metabolites were significantly increased in BS after compatibility. Conclusion: An effective strategy has been developed for screening differences of constituents in vivo before and after compatibility by combining background subtraction and metabolomics. [ABSTRACT FROM AUTHOR]

Background: Polygoni Multiflori Radix (PMR) is a widely distributed herb that has been used for centuries in the treatment of a range of systemic diseases among practitioners of traditional Chinese medicine. Objectives: The present comparative metabolite analysis study was conducted in an effort to understand the relationship between the geographical origin of PMR samples and their medicinal properties. Materials and Methods: As a metabolomics analysis of 35 PMR samples collected from Guangdong and other provinces in China was conducted via ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry. Results: Differential metabolite profiles in these PMR samples were evaluated through multivariate statistical analyses. In total, this approach led to the identification of 778 differential metabolites [value of group contribution (VIP) >1, P < 0.01, and fold-change (FC) >2 or <0.5)] that were primarily associated with glycosaminoglycan degradation, lipoic acid metabolism, flavonoid biosynthesis, tyrosine metabolism, flavone and flavonol biosynthesis, phenylpropanoid biosynthesis, and phenylalanine metabolism. Of these metabolites, catechins accounted for seven significantly altered metabolites (VIP ≥2, P < 0.01, and FC >2 or <0.5) when comparing PMR samples from Guangdong with those from other regions. This suggests that PMR samples contain metabolite profiles characteristic of their provenance. Conclusion: As such, metabolomic profiling may be effective means of differentiating between PMR samples from different geographic regions within China, thus providing a sound theoretical basis for the reliable differentiation among and selection of pharmacologically optimal PMR samples. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacology: Xiaoyaosan (XYS), a famous Chinese prescription, composed of Radix Bupleuri (Bupleurum chinense DC.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Radix Paeoniae Alba (Paeonia lactiflora Pall.), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Poria (Poria cocos (Schw.) Wolf), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Herba Menthae (Mentha haplocalyx Briq.), and Rhizoma Zingiberis Recens (Zingiber officinale Rosc.), has been widely used in the clinic for treating mental disorders. Behavior and biochemical analyses indicate XYS has obvious anti-depression activity. However, there is no report on the effects of XYS using a metabolomics approach. Aim of the study: Depression is a prevalent complex psychiatric disorder and its pathophysiological mechanism is not yet well understood. This paper was designed to study metabonomic characters of the depression induced by chronic unpredictable mild stress (CUMS) and the therapeutic effects of XYS, classic traditional Chinese medicine (TCM) in treating the depression. Material and methods: A plasma metabonomics method based on gas chromatography/mass spectrometry (GC/MS) was developed. Principal component analysis (PCA) was utilized to classify and reveal the differences between the model group and control group. In turns, the concentration of these differences was analyzed with t-test to determine whether XYS was possible to influence the metabolic pattern induced by CUMS. Results: The significant difference in metabolic profiling was observed from model group compared with drug-dose group by using the PCA, indicating the recovery effect of XYS on CUMS rats. Some significantly changed metabolites like glycine, glucose and hexadecanoic acid have been identified. These biochemical changes are related to the disturbance in amino acid metabolism, energy metabolism and glycometabolism, which are helpful to further understand the CUMS and the therapeutic mechanism of XYS. Conclusions: Metabonomic approach is helpful to further understanding the pathophysiology of depression and assisting in clinical diagnosis of depression and is also a valuable tool for studying the essence of Chinese medicine''s syndrome theory and therapeutic effect mechanism of TCM. [Copyright &y& Elsevier]

• Identification of the prototype components of Chaigui granules. • Identification of components in serum, intestinal everted fluid, and brain microdialysate after oral administration with Chaigui granules. • Compare the relative content ofprototype and metabolic components of Chaigui granules in different biosamples. Established qualitative analysis method for Chaigui granules based on UHPLC-Q-orbitrap-MS/MS and applied to its absorption properties studies. The LC–MS method was established to identify the structures of the components and metabolites. And then biosamples of rats after administration, e.g. intestinal solution, serum and brain microdialysate, were detected in rats with same method. Xcalibur 3.2 software was used for mass spectrum analysis and identification. Compound discover 3.0 was used for metabolite analysis. 95 chemical constituents were identified from Chaigui granules, including sesquiterpenes, flavonoids, lactones, tannins, organic acids, saponins and so on. 82 components and 11 metabolites were found in intestinal solution. 28 chemical constituents and 32 metabolites were found in serum. 15 chemical constituents were found in brain microdialysate. Vanillic acid, abiflorin, paeoniflorin, 4-hydroxybenzoic acid, lactiflorin, Z-butylidenephthalide, saikosaponin c, saikosaponin a, atractylenolide III, saikosaponin g, saikosaponin b1, sesquiterpenes, butylphthalide, saikosaponin d and glycyrrhetinic acid directly passed through the blood-brain barrier, which might be speculated that Chaigui granule plays an antidepressant role mainly through regulating brain central mechanism and endocrine mechanism, and so on. It is a systematically applicable approach for rapid identification and relative quantitation of Chaigui granules in vivo by UHPLC-Q-orbitrap-MS/MS, provides an important basis for the safety evaluation and rational clinical application of Chaigui granules. [ABSTRACT FROM AUTHOR]

Radix Bupleuri (Bupleurum chinense DC.) is a traditional Chinese medicine that has the effect of soothing the liver and relieving depression, and widely used in the field of antidepression. The low polarity fraction of Bupleuri Radix (PBR) has proved to be effective for the treatment of depression based on the results of our previous study. However, mechanisms of definite antidepressant-like effects remained unclear. The purpose of this study is to reveal mechanisms of antidepressant-like effects of PBR with multi-dimensional omics. LC-MS metabolomics combined with 16S rRNA gene sequencing were used to investigate the effects of PBR on gut microbiota and metabolites in CUMS-induced depression, and Pearson correlation analysis was carried out on gut microbiota and metabolites. PBR significantly improved depression-like behaviors in the CUMS model rats. Moreover, PBR significantly increased the levels of BDNF in the hippocampus. Cecum contents metabolomics revealed that 16 biomarkers associated with PBR antidepressant effect were screened, which were involved 3 metabolic pathways including primary bile acid biosynthesis, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism. Gut microbiota further analysis demonstrated that PBR increased the diversity of gut microbiota, and significantly inhibited the growth of [Prevotella] and Ochrobactrum. Furthermore, Pearson analysis revealed there was a strong correlation between cecum contents of metabolites and gut microbiota. PBR improved depression-like behavior by regulating metabolic profiles and gut microbiota, and contributing to further understand the entailed antidepressant-like mechanisms of PBR. Image 1 • LC-MS metabolomics combined with 16S rRNA gene sequencing were used to investigate the antidepressant effects of PBR. • PBR improved metabolic profiles and gut microbiota. • There was a strong correlation between metabolites and gut microbiota. [ABSTRACT FROM AUTHOR]

• High-resolution MS and MS/MS data were collected automatically. • The data dependent acquisition was applied to trigger high-intensity precursor ions. • Background subtraction method was applied to reduce solvent interference. • Network pharmacology study was used to predict potential bioactive ingredients of DKD. Dingkun Dan (DKD) has been widely used for a variety of gynecological disease. However, the systematic analysis of the chemical constituents of DKD has not been well established because of the complexity of the formula and confidentiality. In this paper, liquid chromatography Q Exactive high resolution accurate mass spectrometry (UHPLC-QE-HRMS) with automated MetaboLynx analysis was established to characterize the chemical constituents of DKD. The analysis was performed on a Water Acquity UPLC® HSS T3 using a gradient elution system. Full scan ranged 100–1500 m / z in positive and negative ion mode combined with MS/MS fragmentation for top 5 ions was proposed for aiding the structural identification of the components. All of the peaks were tentatively characterized by not only comparing the retention time and MS data with those from reported literature and database, but also summarizing the fragmentation pathways and promoting to other ingredients identification. Additionally, the network pharmacology study had been used to analysis the identified ingredients and DKD's clinical diseases. In this work, a total of 121 components and isomers were characterized, including amino acids, phenolic acids, lactones, terpenoids, alkaloids, saponins, flavonoids, and other compounds. Network pharmacology analysis showed that identified compounds, such as ginsenosides and notoginsenosides, crocin I, echinacoside, rutin and verbascoside, could be responsible for the pharmacological activity of DKD by regulating the hormone with related metabolism pathways, estrogen signaling pathways and serotonergic synapse pathways. It could indicate that UHPLC-MS showed obvious superiority used to find the potential bioactive compounds of complicated TCM formula without the process of extraction and isolation. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Xiaoyaosan (XYS), a well-known formula for relieving depression, was originated from the book of “Taiping Huimin Heji Jufang” in Song Dynasty (960–1127 AD), composed of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae with dose proportion of 6:6:6:6:6:3:2:2. It is commonly used for the treatment of depression-related syndromes in China. In the formula, Radix Bupleuri usually serves as the principal drug, Radix Angelicae Sinensis and Radix Paeoniae Alba serve as the ministerial drugs, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae and Rhizoma Zingiberis Recens serve as adjunctive drugs, Radix Glycyrrhizae serves as messenger drug, they coordinate with each other and enhance the effect of the formula. In our previous experiments, the antidepressant effect of XYS was revealed. However, the antidepressant part (or component) of this prescription was still obscure. Materials and methods: An experimental despair animal model: the mice tail suspension test (TST) was used to evaluate the antidepressant activity of XYS and its fractions. GC–MS method was developed to identify the volatile components and determine 4 major volatile components in active fraction. Results: In the TST test, the effect of a low polar fraction (XY-EA) was superior to other fractions of XYS. 13 volatile compounds in the XY-EA were identified on the basis of standards, isolation and structural determination in our laboratory, NIST 05 database and literature data. The content of 4 major volatile compounds in XY-EA which is 6.703%. Conclusions: The petroleum ether fraction (XY-EA) appears to be the active fraction of XYS. 4 major components Z-ligustilide, palmitic acid, atractylenolide I, and atractylenolide II may be the antidepressant active compounds. [Copyright &y& Elsevier]

Guilingji (GLJ), which has been used to treat male diseases in China for centuries, contains 28 Chinese herbs and was previously established as an effective treatment for male sexual dysfunction. However, its mechanism of action remains unclear. To explore the efficacy and mechanism of action of GLJ in improving senile sexual dysfunction (SSD) in aging rats. An aging rat model of SSD was induced by the subcutaneous injection of d -galactose (300 mg⋅kg-1) and used to analyse the effects of GLJ (different concentrations of 37.5, 75, and 150 mg⋅kg-1) on the mating of aging rats. At the end of the 8th week, histopathological analysis of testicular tissues, assessment of the hypothalamic-pituitary-gonadal (HPG) axis hormone levels in serum or brain, and metabonomics analysis of the brain and testicular tissue with liquid chromatography–mass spectrometry was performed to explore the mechanism of action of GLJ. After treatment with GLJ, the mount and ejaculation latency levels were increased in the treatment group than those in model group (P < 0.05), moreover, the testicular morphology was improved. Gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) levels in rats were also improved significant (P < 0.05) compared with those in the model group. Furthermore, the metabonomics results in the testicular and brain tissue showed that GLJ improved SSD by adjusting amino acid and lipid metabolism. This study integrated the complementary metabolic profiles of the target tissues. GLJ might affect SSD rats by regulating amino acid and lipid metabolism and may modulate sensitivity to the signaling pathway in the HPG axis. This study provides an essential basis for the broad clinical application of GLJ. [Display omitted] • Guilingji improved the sexual ability of aging rats. • The study illustrated the mechanisms of the effects of Guilingji on Senile Sexual Dysfunction rats by metabonomics. • 12 metabolites in brain tissues and 14 in testicular tissues were significantly restored by Guilingji. • Amino acid metabolism and lipid metabolism might be the most important metabolic pathways regulated by Guilingji. [ABSTRACT FROM AUTHOR]

Xiaoyaosan (XYS), a famous and classic traditional Chinese prescription, has been used for long time in treating depressive disorders. XYS consists of Radix Bupleuri (Bupleurum chinense DC.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Radix PaeoniaeAlba (Paeonia lactiflora Pall.), Rhizoma Atractylodis Macrocepha lae (Atractylodes macrocephala Koidz.), Poria (Poria cocos (Schw.)Wolf), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Herba Menthae Haplocalycis (Mentha haplocalyx Briq.), and Rhizoma Zin-giberis Recens (Zingiber officinale Rosc.). A GC-MS based metabolomics approach was applied to discover the potential biomarkers that were related to metabolic differences between healthy volunteers and depression cohort diagnosed by HAMD and CGI, and to demonstrate the potential utility of these biomarkers in the diagnosis of depression and pharmaceutical efficacy of XYS. A total of 17 depressed patients and the 17 age- and gender-matched healthy subjects were served as the primary cohort. The depressed patients were screened according to the Chinese Classification of Mental Disorder (CCMD-3) and the Hamilton Depression Scale (HAMD). In addition, five other depressed patients were also enrolled as the primary cohort when the final step of sample collection was conducted. Plasma samples were analyzed by Gas Chromatography-Mass Spectrometry (GC-MS). Clinical and metabolomics data were analyzed by multivariate statistics analysis, Receiver Operating Characteristic (ROC) curve and MetaboAnalyst. We observed significant differences between depression cohort and healthy volunteers, and between patients before and after the treatment of XYS. The method was then clinically validated in an independent validation cohort. Levels of oxalic and stearic acids significantly increased in depressed patients' plasma while valine and urea significantly decreased, as compared with healthy controls. Of note, XYS reversed these metabolite changes in terms of regulating dysfunctions in glyoxylate and dicarboxylate metabolism, fatty acid biosynthesis, valine, leucine and isoleucine biosynthesis, and arginine and proline metabolism. Importantly, the combination of oxalic and stearic acids is in prospect as diagnose biomarkers. This study highlights the clinical application of metabolomics in disease diagnose and therapy evaluation, which will help in improving our understanding of depression and will lay solid foundation for the clinic application of TCMs. In addition, it suggests that the combination of the two potential biomarkers had also achieved a high diagnostic value, which consequently could be used a diagnose biomarkers. Image 1 • Depressed patients had dysfunctions in both metabolic profiles and clinic symptoms. • XYS reversed the changes of metabolic profiles and clinic symptoms of depression. • The combination of two potential biomarkers are potential as diagnose biomarkers. • Metabolomics-based approach is a potential diagnostic tool for clinical diseases. [ABSTRACT FROM AUTHOR]