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Highlights • Morinda officinalis (MO) mitigates the bone loss induced by glucocorticoid in rats. • MO enhances the bone formation of glucocorticoid-injured osteoblasts. • MO reverses the bone loss in GIOP rats by intervening arachidonic acid pathway. Abstract Morinda officinalis (MO) has long been used as a traditional herbal medicine for the treatment of bone fractures and joint diseases in China. Monotropein (Mon) and rubiadin-1-methyl ether (Rub) are major bioactive components in MO. Ample evidence shows that MO and its chemical constituents can prevent osteoporosis induced by estrogen-deficiency and ageing. However, there is no study reporting glucocorticoid-induced osteoporosis (GIOP). The aim of the present study was to explore the protective effect of MO on GIOP modeled rats and osteoblasts, and elucidate the underlying mechanisms via UHPLC-Q-TOF/MS based metabolomics profiling. Eight weeks after dexamethasone (DEX) injection and MO treatment in female SD rats aged 12 weeks, bone mineral density (BMD), the micro-architecture of the trabecular bone, serum level of bone metabolism markers, and urine metabolomics were assayed in vivo. Cultured osteoblasts were injured with DEX, and the effects of MO, Mon and Rub on osteoblastic proliferation, differentiation and mineralization were examined in vitro. The results showed that MO was able to increase BMD, improve the micro-architecture and intervene bone metabolism via regulating alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP) and c-terminal telopeptides of type I collagen (CTX-I) levels in DEX-treated rats. The in vitro experiment showed that MO, Mon and Rub all increased the cell proliferation and ALP activity, and enhanced extracellular matrix mineralization in DEX-injured osteoblasts. Metabolomics profiling identified a total of 37 differential metabolites in DEX group vs. the control group, of which 20 were reversed significantly after MO treatment. Further metabolic pathway enrichment and Western blotting analysis showed that MO prevented bone loss mainly by interfering with arachidonic acid metabolism. These results suggested MO had a notable anti-GIOP effect, and the underlying mechanisms might be related to arachidonic acid metabolism. [ABSTRACT FROM AUTHOR]

Qi-Fu-Yin (QFY), a classical traditional Chinese medicine formula, is proven to have significant neuroprotective effects by modern pharmacological studies. However, the chemical constituents of QFY have not been fully explored. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF MS) was developed for comprehensive analysis of chemical constituents in QFY. By using characteristic ions and fragmentation rules, a reliable identification of 156 compounds was described here, including 69 triterpene saponins, 23 oligosaccharide esters, 22 flavanoids, 9 alkaloids, 9 phenolic acids, 8 phthalides, 7 phenylethanoid glycosides, 3 xanthones, 3 sesquiterpene lactones, 2 ionones and 1 iridoid glycoside. Twenty-six major compounds were then determined in a single run by UHPLC coupled with triple quadrupole tandem mass spectrometry (QQQ MS) with fast positive/negative polarity switching. It allows for the acquisition of MS data in both ionization modes from a single run. The proposed method was then validated in terms of linearity, accuracy, precision and recovery. The overall recoveries for 26 analytes ranged from 91.35% to 109.58%, with RSDs ranging from 0.82% to 4.83%. In addition, the content of 26 analytes in QFY prepared by five batches of herbal materials was also analyzed. These results demonstrated that our present method was effective and reliable for comprehensive quality evaluation of QFY. Meanwhile, the study might provide the chemical evidence for revealing the material basis of its therapeutic effects. [ABSTRACT FROM AUTHOR]

A rapid ultra-high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-Q-TOF/MS) method was developed for qualitative and quantitative determination of constituents in the rhizome of Curculigo orchioides . Qualitative analysis was performed on a Waters ACQUITY UHPLC @ HSS T3 column (1.8 μm 100 × 2.1 mm) using gradient elution with mobile phase of 0.1% formic acid and acetonitrile. Quantitative analysis was performed on an Agilent ZORBAX Eclipse plus C18 column (1.7 μm 100 × 2.1 mm) using gradient elution with mobile phase of 0.1% acetic acid and acetonitrile for at least 20 min. Quadrupole TOF/MS in either full scan mode or extracted ion mode was used for qualitative and quantitative analysis of the constituents. According to the mass spectrometric fragmentation mechanism and UHPLC-ESI-Q-TOF-MS data, chemical structures of 45 constituents in the rhizome of Curculigo orchioides , including 19 phenols and phenolic glycosides, 16 lignans and lignan glycosides, 8 triterpenoid saponins, one flavone and one sesquiterpene, were identified tentatively on-line without the time-consuming process of isolation. In addition, 8 phenolic glycosides including 5-hydroxymethylfurfural (HMF), 2-hydroxy-5-(2-hydroxyethyl) phenyl-β- d -glucopyranoside (HPG), anacardoside (ACD), orcinol glucoside (OGD), orcinol-1-O-β- d -apiofuranosyl-(1 → 6)-β- d -glucopyranoside (OAG), 2,6-dimethoxybenzoic acid (DBA), curculigoside (CUR) and curculigine A (CCL) were quantitated in 11 collected samples and 10 commercial samples from different providers. The results show that UHPLC-ESI-Q-TOF-MS is a viable method for analysis and quality evaluation of the constituents from the rhizome of Curculigo orchioides. [ABSTRACT FROM AUTHOR]

Highlights: [•] A practical approach for metabolism of chiral drugs was based on combined LC/MS/MS. [•] Racemic tetrahydropalmatine was chosen as the model chiral drug. [•] UPLC-QTOF/MS was used to identify the metabolites of THP enantiomers in rat urine. [•] LC-QqQ/MS was applied for quantification of THP enantiomers and their metabolites. [•] Semi-quantification of three phase I and two phase II metabolites was performed. [Copyright &y& Elsevier]

• The catanionic surfactant vesicles were used to disaggregate carbon nanotube bundles. • Micellar extraction was employed for the sample pre-extraction. • The relative parameters were optimized using response surface methodology. Here, catanionic surfactant vesicles were prepared by varying the types and compositions of anions and cations and the number of alkyl tails of the surfactants. The formed vesicles were employed to disaggregate and stabilize multiwalled carbon nanotubes bundles in aqueous solutions. Furthermore, the vesicle coated carbon nanotubes were used as the adsorbent in the dispersive micro-solid phase extraction. Additionally, micellar extraction was employed for the sample pre-extraction to avoid the use of toxic organic extraction solvents. The relative parameters that affect the extraction efficiency of targets were optimized using response surface methodology. Under the optimal microextraction conditions, the analytical performance of the established method was evaluated. The limits of detection (2.3−13 ng/mL) and quantification (7.6−42 ng/mL), inter- and intra- day precision (1.2–4.0 %, 2.0–5.0 %), and spiked recovery values (80–91 %) were obtained. The proposed method showed high sensitivity, precision and trueness. It was successfully applied to analyze phenols in Dendrobium genus samples. [ABSTRACT FROM AUTHOR]

This study aimed to develop a specific and reliable method to comprehensively analyze the chemical constituents in Shengmai injection (SMI) using high performance liquid chromatography coupled with tandem mass spectrometry. The qualitative analysis of SMI was achieved on a Kromasil 100–5C 18 column, and the results demonstrated that a total of sixty-two compounds in SMI were unambiguously assigned or tentatively identified, and further, twenty-one compounds including fourteen saponins, six lignans and one l -borneol-7- O -[β- d -apiofuranosyl (1 → 6)]-β- d -gluco-pyranoside were quantified by HPLC–MS. Furthermore, l -borneol-7- O -[β- d -apio-furanosyl (1 → 6)]-β- d -glucopyranoside, originated from Radix ophiopogonis, was identified and quantified in SMI for the first time. The method validation results indicated that the methods were simple, specific and reliable. All the investigated compounds showed good linearity ( r 2 ≥ 0.9992) with a relatively wide concentration range and acceptable recovery at 90.13–109.09%. Consequently, the developed methods were successfully applied to ten batches of SMI samples analysis. The proposed methods may provide a useful and comprehensive reference for the quality control of SMI, and thus to provide supporting data for the quality control and application of SMI clinically. [ABSTRACT FROM AUTHOR]

Miltirone is one of the bioactive diterpene quinones isolated from Salvia miltiorrhiza Bunge. This compound has been found to possess significant anticancer, antibacterial, antioxidant, and anti-inflammatory activities. However, the metabolic fate of miltirone remains unknown. In order to explore whether miltirone is extensively metabolized, we investigated the metabolites of miltirone in plasma, bile, urine, and feces samples following oral and intravenous administration to the rats. By using high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF-MS) coupled with mass detect filter (MDF) method, a total of 15 metabolites were identified from the biosamples. Both phase I and phase II metabolites were observed in the metabolic profile and the metabolic pathways involved in reduction, oxidation, monohydroxylation, dihydroxylation, glucuronidation and sulfation. The results indicated that hepatocyte metabolism was the major route of clearance for the parent compound. The present study provided valuable information for better understanding of the efficacy and safety of miltirone. [ABSTRACT FROM AUTHOR]

Highlights: [•] A reliable strategy was developed for xenobiotic metabolome identification of TCM. [•] The S- and VIP-plot can clearly display leading contributing markers. [•] A total of 102 SND-related xenobiotic metabolites were characterized. [•] The metabolite profiles of major components from SND in rat urine were described. [ABSTRACT FROM AUTHOR]

Abstract: A serum metabonomic profiling method based on ultra-performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS) was applied to investigate the metabolic changes in hypothyroid rats induced by propylthiouracil (PTU). With Significance Analysis of Microarray (SAM) for classification and selection of biomarkers, 13 potential biomarkers in rat serum were screened out. Furthermore, Ingenuity Pathway Analysis (IPA) was introduced to deeply analyze unique pathways of hypothyroidism that were primarily involved in sphingolipid metabolism, fatty acid transportation, phospholipid metabolism and phenylalanine metabolism. Our results demonstrated that the metabonomic approach integrating with IPA was a promising tool for providing a novel methodological clue to systemically dissect the underlying molecular mechanism of hypothyroidism. [Copyright &y& Elsevier]

• Zirconium metal-organic framework was synthesized and used as adsorbent material. • Mini-SPE was investigated for the preconcentration of phenylurea herbicides. • The innovative method was simple, green, low cost, rapid, and high sensitivity. • The method was applied in natural products. • The target analytes were detected by UHPLC-Q-TOF/MS. The zirconium metal-organic framework (Zr-MOF) was used as a novel and effective adsorbent material for the enrichment of five phenylurea herbicides (fenuron, monuron, diuron, linuron and pencycuron) in natural products. The target analytes were determined by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Some crucial experimental parameters, such as type of adsorbents, amount of adsorbent, type of eluent solvents and adsorption capacity were investigated and optimized. Under the optimum extraction conditions, the enrichment factors of fenuron, monuron, diuron, linuron and pencycuron were 90, 128, 148, 204 and 295 times, respectively. A good linearity was obtained in different concentration levels of target analytes with the determination coefficients (r2) larger than 0.993. In addition, the limits of detection varied from 0.05 to 0.36 ng/mL and the recoveries of the analytes were in the range of 85.19–99.13 %. The results demonstrated that the proposed miniaturized solid-phase extraction procedure coupled with Zr-MOF could become an effective tool to analyze phenylurea herbicides and would have the vast application prospect for the extraction of pesticide residue and more organic pollutants from Hawthorn, Dendrobii Officinalis Caulis and Salviae Miltiorrhizae Radix et Rhizoma samples. [ABSTRACT FROM AUTHOR]

Highlights • GC–MS, RPLC-MS and HILIC-MS metabolomic assessed the efficacy of SFI on AVMC. • Computational systems analysis identified SFI-targeted metabolic pathways. • RT-PCR analysis validated the key enzymes in the SFI-targeted pathways. Abstract Acute viral myocarditis (AVMC) is typically caused by cardiotropic viral infection. There is a paucity of specific treatment options available with proven efficacy. Chinese patented pharmaceutical product Shenfu injection (SFI) has potent efficacy on treating AVMC in clinical practice. However, the molecular mechanism is still unknown. We employed cross-platform metabolomics combined with computational systems analysis, based on reversed-phase liquid chromatography–mass spectrometry (RPLC-MS), hydrophilic interaction liquid chromatography–mass spectrometry (HILIC-MS) and gas chromatography-mass spectrometry (GC–MS), to deciphering the targeted metabolic pathways of SFI against AVMC induced by coxsackievirus B3 (CVB3). Quantitative real-time PCR (qRT-PCR) technique was further applied to determining the expressions of the key genes associated with the SFI-targeted metabolic pathways. We have identified 48 significantly changed metabolites related to CVB3-induced AVMC, and SFI can significantly regulate the abnormalities of 33 metabolites and 9 relevant enzymes. Combined metabolic pathway enrichment and topology analyses revealed that the mechanisms of SFI against CVB3-induced AVMC may be attributed to modulating the disordered homeostasis of sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, tryptophan metabolism, and TCA cycle. It provides new experimental information on the pathogenesis of AVMC, unravels the potential targeted metabolic pathways of SFI against AVMC on the whole metabolic network and highlights the importance of metabolomics combined with computational systems analysis as a potential tool for deciphering drug-targeted metabolic pathways. [ABSTRACT FROM AUTHOR]

The herbal pair Zhimu-Baihe (Zhimu: Anemarrhena asphodeloides ; Baihe: Lilium brownii var. viridulum ) is a traditional Chinese medicament used for the treatment of depression. However, the relevant mechanisms of action has not been clarified. This study investigated the anti-depressant activity of the total saponins from Zhimu and Baihe and the mechanisms underlying using a chronic unpredictable mild stress (CUMS)-induced rat model of depression. High performance liquid chromatography with electrochemical detection (HPLC-ECD) was applied to determine the levels of three monoamine neurotransmitters, 5-hydroxytryptamine (5-HT), noradrenaline (NE) and dopamine (DA), in the rat hippocampus. Optimized pretreatment of samples and mass spectrometry conditions were used to analyse the metabonomic profile of the hippocampus. The 5-HT and NE levels in the CUMS group were reduced compared with the control group, whereas all groups had similar DA levels. The metabonomic profile of the hippocampus revealed 32 differential metabolites between the CUMS and control group, among which 18 metabolites were significantly recovered in the Anemarrhena saponins and Lilium saponins (AL) combination intervention group. These results suggested an anti-depressant effect of AL. Moreover, 24 metabolites in AL group were better recovered compared with the Anemarrhena saponins (AS) or Lilium saponins (LS) intervention groups, suggesting a synergetic effect of AS and LS in the treatment of depression. The anti-depressant effect might be related to the regulation of several metabolic pathways, including monoamine neurotransmitter synthesis (especially 5-HT and NE), and amino acid, fatty acid, and phospholipid metabolism in rats. [ABSTRACT FROM AUTHOR]

Thrombin plays a significant role in thromboembolic disease. In this work, a peak fractionation approach combined with an activity assay method was used to screen direct thrombin inhibitors from Radix Salviae Miltiorrhizae (RSM), a famous herbal remedy for the treatment of cardiovascular diseases in China. A total of 91 fractions were collected from the RSM extract, and 19 fractions out of them showed thrombin inhibitory effects with dose–effect relationship. Among them, three compounds were unambiguously identified as 15, 16-dihydrotanshinone I, cryptotanshinone and tanshinone IIA with IC 50 values of 29.39, 81.11 and 66.60 μM, respectively. The three compounds were reported with direct thrombin inhibition activities for the first time and their ligand–thrombin interactions were explored by a molecular docking research. These results may contribute to explain the medical benefit of RSM for the prevention and treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a convenient method without pretreatments for nontarget discovery of interested compounds. The segment and exposure strategy, coupled with two mass spectrometer data acquisition methods was firstly proposed for screening the saponins in extract of Panax notoginseng (Sanqi) via high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC-QTOF/MS). By gradually removing certain major or moderate interference compounds, the developed segment and exposure strategy could significantly improve the detection efficiency for trace compounds. Moreover, the newly developed five-point screening approach based on a modified mass defect filter strategy and the visual isotopic ion technique was verified to be efficient and reliable in picking out the interested precursor ions. In total, 234 ginsenosides including 67 potential new ones were characterized or tentatively identified from the extract of Sanqi. Particularly, some unusual compounds containing the branched glycosyl group or new substituted acyl groups were firstly reported. The proposed integrated strategy held a strong promise for analyses of the complex mixtures. [ABSTRACT FROM AUTHOR]

Spatholobi Caulis, the vine stem of Spatholobus suberectus Dunn, has been widely used in traditional Chinese and folk medicines for treatment of irregular menstruation, blood deficiency and rheumatalgia in clinic. In this study, an accurate and reliable high performance liquid chromatography/electrospray ionization triple quadrupole mass spectrometry (HPLC–MS/MS) method was established for simultaneous determination of 16 phenolic bioactive constituents, including five flavanols, seven isoflavonoids, three flavanones and one chalcone in Spatholobi Caulis. The method validation results exhibited that the developed method had desirable specificity, linearity, precision and accuracy. The quantitative analysis results showed that flavanols were the abundant constituents in Spatholobi Caulis. Moreover, principal component analysis (PCA) was performed to assess the quality variation of samples collected from different regions in China. The PCA results indicated the quantitative analysis based on HPLC–MS/MS is a feasible method for quality assessment and control of Spatholobi Caulis. [ABSTRACT FROM AUTHOR]

Relative quantification of multi-components in complex mixture is significantly affected by the ionization variance caused by mobile phase composition in high-performance liquid chromatography with electrospray ionization mass spectrometry (HPLC–ESI-MS) analyses. The normalization methods for eliminating the variance are still less investigated. Herein, the mobile-phase compensation (MPC) method was applied to overcome the above problem. The developed method was firstly used for convenient evaluation of the coeluent interference and subsequently applied for relative quantification of the identified multi-components in Panax notoginseng (Sanqi) samples. The good linearity, precision and low limit of quantification of targeted analytes confirmed that the MPC–HPLC–ESI-MS method in gradient elution could achieve the isocratic test results compared with classical HPLC–ESI-MS. The established method was used for relative quantification of the minor Sanqi saponins by their detected peak areas divided by that of ginsenoside Rd. The results demonstrated the potential of the newly developed method for obtaining the normalized data shared in different laboratories. [ABSTRACT FROM AUTHOR]

This is the first attempt that combining mechanochemistry and enzymes to simultaneously evaluate phenolic compounds from plant by UHPLC-QTOF-MS. • Novel eco-friendly mechanobiological assisted extraction method was developed. • The identification of different phenolic compounds was performed by UHPLC-QTOF-MS. • The developed method was more efficient and eco-friendlier for the extraction. • The proposed method was optimized by the response surface methodology. A novel mechanobiological assisted extraction (MBAE) method was developed for simultaneous extraction of phenolic acids and flavonoids from Chrysanthemum morifolium. Optimization of extraction factors was performed by response surface methodology based on the Box-Behnken design. The optimal parameters for MBAE were as follows: the amount of enzyme 1% (wt−1), cellulase/pectinase ratio 2:1 (mgmg−1), enzyme solution pH 4.88, extraction pH 10.0, grinding time 40 min and liquid/solid ratio 20:1 (mL/g). Five target compounds flavonoids were identified and quantified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry in a negative mode. Under optimum conditions, the standard calibration curves were linear in the range of 0.01-20 μg mL−1 and the correlation coefficients were above 0.999 with recoveries of 87.74-119.96%. The developed MBAE method showed the advantages of efficient, time-saving and environmentally friendly which had greater extraction capacity than conventional organic extraction. This is the first attempt that combining mechanochemistry and enzymes to simultaneously extraction phenolic acid and flavonoids from plant. [ABSTRACT FROM AUTHOR]