Search

This study describes the effectiveness of post-acquisition data processing techniques in detecting the lipid species rapidly from the massive data generated by high resolution mass spectrometry. The filtering approaches by product ions or neutral losses enabled glycerophospholipids and sterol conjugates to be identified based on the investigation of their fragmentation patterns, and the filtration by mass defect facilitated the detection of fatty acyl residues and bile acids by limiting the range of mass defect values. After application of these filtering techniques to mass spectra, the background noise was significantly filtered out and characteristic peaks of lipid species were efficiently sorted out. Totally 145 individual lipids were identified and structurally elucidated. Validation results of the LCMS-Q-TOF-based quantitative performance for all the peaks showed that the accuracy, expressed as relative errors (RE%), was lower than ±15%, and values (RSD%) of the inter-batch and intra-batch precision were lower than 15% in the assay. The developed method was integrated to the evaluation of plasma lipid profile from high fat diet versus energy restricted diet fed rats. A unique discrimination of the groups was successfully achieved through a principal component analysis (PCA)., (Copyright © 2012. Published by Elsevier B.V.)

This study was to develop and evaluate a practical approach of mass defect filtering (MDF), a post-acquisition data processing technique, for the rapid classification of complicated peaks into well-known chemical families based on the exact mass acquired by high resolution mass spectrometry. The full-scan LC-MS/MS data of the Ophiopogon japonicus extract was acquired using high performance liquid chromatography coupled with hybrid quadrupole-time of flight (LCMS-Q-TOF) system which features high resolution, mass accuracy, and sensitivity. To remove the interferences of the complex matrix, MDF approach was developed and employed to rapidly pick out the peaks of ophiopogonins and ophiopogonones from full-scan mass chromatograms. The accuracy of MDF was evaluated in reference to the result of structural identification. After the MDF based classification, both target and non-target components in Ophiopogon japonicus extract were characterized based on the detailed fragment ions analysis in the hybrid ion trap and time-of-flight mass spectrometry (LCMS-IT-TOF). By this approach, more than 50 ophiopogonins and 27 ophiopogonones were structurally characterized. The present results of rapid detection and identification of ophiopogonins and ophiopogonones suggest that the proposed MDF approach based on the high-resolution mass spectrometry data would be expected adaptable to the analysis of other herbal components., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We report herein, a facile metabolite identification workflow on the antimicrobial strictosamide, which is derived from accurate mass measurement by a hybrid ion trap-TOF mass spectrometer. In step 1, the parent drug and metabolites in rat bile were separated on an HPLC column followed by ion trap-TOF mass spectrometer analysis after a single oral dose of 50mg/kg strictosamide. In step 2, mass defect filter technique, which enables high-resolution mass spectrometers to be utilized for detecting drug metabolites based on well-defined mass defect ranges, was used to find metabolites in the mass spectrum. In step 3, the differences of accurate masses and their mass fragmentation pattern among the parent drug and metabolites used to assign structures for the metabolites successfully. As a result, five metabolites of strictosamide were found in rat bile, and all the metabolites were reported for the first time., (Copyright © 2011 Elsevier B.V. All rights reserved.)

To date, the pharmacokinetic research of herbal medicines (HMs) is still in its infancy and is facing critical technical challenges on the qualitative and quantitative analysis of complicated components from biological matrices. Additionally, the lack of authentic standards constitutes another bottleneck on assessing herbal pharmacokinetics. This present work contributes to the development of a powerful technical platform for both qualitative and quantitative pharmacokinetic analysis of herbal components, and a strategy of relative exposure that provides a practicable pharmacokinetic assessment independent of authentic standards, based on the use of liquid chromatography hybrid ion trap time-of-flight mass spectrometry (LC-IT-TOF/MS). Taking schisandra lignans extract (SLE) as an example, the LC-IT-TOF/MS assay was initially applied to the global qualitative analysis of components contained in SLE per se and in the rat plasma post SLE dosing. Afterwards, this study focused on validating the quantitative performance of LC-IT-TOF/MS assay by comparison with a well-established LC-Q/MS assay. For the absolute quantification of five lignans components with authentic standards, both assays showed very similar analytical figures of merit such as linearity, precision, accuracy, and pharmacokinetic parameters. Compared with LC-Q/MS, the prominent advantage of LC-IT-TOF/MS assay is its much higher sensitivity. Moreover, a 'relative exposure approach' (REA) that entails the use of sequentially diluted original herbal preparations to prepare the 'mixed calibration curves' was developed to assessing herbal pharmacokinetics independent of specific authentic compounds for each component. Such an approach was found capable of providing virtually identical pharmacokinetic parameters as that from the typical pharmacokinetic assay calibrated by authentic standards, except for the absolute plasma concentrations. The presently developed methodology and approach will find its wide use in, but not limited to, the qualitative and quantitative pharmacokinetic analysis of herbal medicines., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Quadrupole (Q) mass spectrometers are the most popular analytical tools due to their reliability, effectiveness, and low cost. However, they are not suitable for quantitative analysis of multi-component since the sensitivity will get worse rapidly with the increasing number of m/z detected. The present work, for the first time, attempted to analyze of 16 saponins simultaneously using an approach of segmental and selected ion monitoring (SSIM) based on LC-Q/MS, and systematically investigated the influence of different SSIM modes on signal level/noise level (S/N), lower limits of quantification (LLOQ), upper limits of quantification (ULOQs), etc. Our results showed that a proper SSIM mode could not only provide much higher sensitivity for all the targeting analytes, but also dramatically broadened their dynamic ranges. The developed methodology could effectively break the application bottleneck on the quantitative analysis of multi-component with LC-Q/MS, and would be applied widely in related fields for multi-component analysis, such as environmental monitoring, metabonomics, Chinese herbal medicine research., (Copyright 2010 Elsevier B.V. All rights reserved.)

We describe herein, a very effective way in the rapid identification of metabolites for antofloxacin based on a hybrid ion trap (IT)/time-of-flight (TOF) mass spectrometer technique. The purified samples were separated by a reversed-phase C18 column under a gradient elution, antofloxacin and its metabolites were detected by the on-line IT/TOF detector in scan mode. The identification of the metabolites and elucidation of their structure were performed by comparing the changes in molecular masses (DeltaM), calculating compound-based component by Formula Predictor software, and defining sites of biotransformation based upon mass shifts of diagnostic fragment ions according to the accurate MSn spectral information. In this case, we used such strategies for the identification of the metabolism for antofloxacin, and six metabolites of antofloxacin were found in rats for the first time.

Aging plays an important role in the formation of aroma characteristics of Huangjiu, a traditional Chinese alcoholic beverage. Comprehensive two‐dimensional gas chromatography mass spectrometry (GC×GC‐qMS)‐based untargeted metabolomics combined with a multivariate analysis was used to investigate the dynamic variations in the aroma profile of Huangjiu during aging process and to establish the relationship between the changing volatile metabolite profiles and the age‐dependent sensory attributes. A total of 144 volatile metabolites were identified by GC×GC‐qMS and 63 were selected as critical metabolites based on variable importance in projection values and p‐values. Based on the results of principal component analysis, orthogonal partial least‐squares discriminant analysis, and hierarchical clustering analysis, the samples of six different ages were divided into three groups: 1Y and 3Y samples, 5Y and 8Y samples, and 10Y and 15Y samples. The partial least‐squares analysis results further revealed the relationship between the aromas attributes and variations of these volatile compounds. The high esters, aldehydes, and lactones contents contributed to the high intensities of the sweet and ester aroma attributes of the aged Huangjiu, while the high alcohols and ethyl esters contents contributed to the alcoholic and fruity aroma attributes of the newly brewed Huangjiu. These results improve our understanding of the chemical nature of the aroma characteristics of aged Huangjiu. Practical Application: Huangjiu is often labeled with its age as a measure of quality, which influences consumers' choice. Dynamic variations in volatile compounds of Huangjiu during aging and its contribution to the aroma characteristics of Huangjiu were figured out, which will assist the industry to produce better quality aged Huangjiu for consumers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chinese rice wine (CRW) is a kind of traditional fermentation wine in China. Aged CRW is more popular among consumers owing to its harmonious and pleasant flavor. The volatile profile of CRW has been extensively studied using gas chromatography/mass spectrometry (GC/MS). However, flavor components in CRW are far richer than those detected by GC/MS. To obtain more information about the volatile profile of fresh (5‐year) and aged (10‐year) CRW, a method based on comprehensive two‐dimensional gas chromatography coupled to quadrupole mass spectrometry (GC×GC/qMS) was developed. The major volatile compounds contributing to the characteristic aroma of fresh and aged CRW were identified by surrogate odor activity value (OAV). RESULTS: Ninety‐eight volatile compounds were detected in the 5‐year CRW samples and 107 in the 10‐year samples by GC×GC/qMS. The numbers of compounds detected by GC×GC/qMS for the 5‐year and 10‐year samples were 71.4 and 65.4% higher than those detected by GC/MS. The aged wine had a more complex volatile profile than the fresh wine, with an increase in esters and aldehydes and a decrease in alcohols and organic acids. There were 22 volatile compounds with surrogate OAV > 1. Nine were the potent key aroma compounds in CRW: ethyl isovalerate (OAV 500–33 500), ethyl butyrate (OAV 84–334), ethyl isobutyrate (OAV 49–170), 2‐nonenal (OAV 20–100), ethyl heptanoate (OAV 1–74), ethyl hexanoate (OAV 60–77), phenylethyl alcohol (OAV 2–18), benzaldehyde (OAV 28–30) and hexanal (OAV 4–11). CONCLUSION: GC×GC/qMS showed better separation than GC/MS. The presented GC×GC/qMS method was suitable for characterization of the volatile profile of CRW. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Jinxin oral liquid (JOL) is a traditional Chinese medicine (TCM) formula modified from ma-xing-shi-gan-tang, an ancient formula widely used in the treatment of respiratory diseases such as bronchitis, pneumonia, and asthma. In our previous studies, JOL was shown to safely and effectively treat viral pneumonia, especially that involving respiratory syncytial virus (RSV). Aim of the study To investigate the mechanism of the effect of JOL in RSV infected mice, using a metabolomics approach based on ultra-performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap–MS). Materials and methods BALB/c mice were divided into four groups, the control group (saline inoculation/no treatment), RSV group (RSV inoculation/saline treatment), RSV+JOL group (RSV inoculation/JOL treatment), and RSV+Riba group (RSV inoculation/ribavirin treatment). Plasma and lung tissue samples were collected 7 days after the inoculation/treatment protocols, and UPLC/LTQ-Orbitrap-MS method based on metabolomics was developed. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify biomarkers potentially associated with the anti-RSV activity of JOL. Results JOL was associated with reduced inflammatory responses in RSV-infected lung tissue. The combination of PCA and OPLS-DA revealed deviations in 11 biomarkers in plasma, and 16 biomarkers in lung tissue induced by RSV that were corrected with JOL treatment. These biomarkers were primarily components of metabolic pathways involving glycerophosphocholines, sphingolipids, and glycerolipids. JOL was able to restore the abnormal levels of these biomarkers detected in the plasma and lung tissue of RSV-infected mice to approximately normal levels. Conclusions This study suggested that JOL can treat RSV pneumonia effectively, partially by ameliorating the associated disturbances to lipid metabolism. The results provided insight into the anti-RSV mechanism of JOL, and also demonstrated that metabolomics is a valuable tool for investigating the efficacy of TCM treatment for RSV pneumonia, and the associated biomarkers involved. [ABSTRACT FROM AUTHOR]

The plasma pharmacokinetics, tissue distribution, excretion, and metabolism of 10-O-dimethylaminoethylginkgolide B (XQ-1H), a protective agent against cardiovascular accident for its potential anti-platelet-activating factor activity, were investigated in rats. Plasma profiles were obtained after intravenous administration of 4, 8, 16, and 32 mg/kg of XQ-1H. There was a gender difference in the pharmacokinetics of XQ-1H. The elimination half-life of XQ-1H was 209.55, 200.81, 236.95, and 269.78 min in female rats and was 139.63, 173.83, 191.28, and 228.0 min in male rats at doses of 4, 8, 16, and 32 mg/kg, respectively. At four dose levels, female rats have higher values for area under the curve (AUC) than male rats. XQ-1H had linear pharmacokinetic characteristics in rats within the dose ranges tested. The volume of distribution in rats ranged from 6.05 to 15.09 l/kg. XQ-1H showed an extensive distribution into multiple tissues and reached its maximal concentration in all tissues at 10 min post-dose. About 80% of XQ-1H was mainly converted to its hydrolyzed and demethylated metabolites in vivo, and the elimination of unchanged compound was minor ( < 20%) in rats. [ABSTRACT FROM PUBLISHER]

• Spectral similarity is used to find the deviated annotations. • Fragment interpretation is integrated to evaluate the confidence. • Annotation confidence are well ranked by the proposed score system. • The method has been proved effective in Platycodon grandiflorum and Licorice. Tandem mass spectrometry-spectra-based annotation in natural products challenges a lot because of ambiguous structural characterization. It still lacks an efficiency method to score and rank the annotation confidence. Herein, we develop a novel approach to rank the annotation confidences of saponins. Annotations were accomplished according to fragmentation patterns. The corresponding diagnostic fragments and their abundances were recorded. Average abundances were taken as a reference spectrum, and the cosine similarity score (CSS) was calculated to measure how well the spectral matched. According to CSS values, statistic description for confidence levels can be effectively provided. Next, the fragment interpretation score (FIS) was proposed to investigate the deviators' characteristic fragmentation. FIS offset the effect from the deviators' unique fragments. Suspicious annotations involving low CSS and high FIS, may derived from the MS2 spectral background interferences or co-elution. Annotations with low CSS and FIS rank as low confidences, as these annotations need more attention. Using this method, novel saccharide sequences, specific fragmentation preferences, undistinguished precursors, even new structures can also be well traced. By proposed new scoring system, confidence evaluations can be ranked, resulting in significantly enhanced annotation reliability. [ABSTRACT FROM AUTHOR]

Surfactant lipid metabolism is closely related to pulmonary diseases. Lipid metabolism disorder can cause lung diseases, vice versa. With this rationale, a useful method was established in this study to determine the lipidome in bronchoalveolar lavage fluid (BALF) of mice. The lipid components in BALF were extracted by liquid–liquid extraction (methanol and methyl tert-butyl ether, and water). Ultra-high-performance liquid chromatography coupled to hybrid Quadrupole-Exactive Orbitrap mass spectrometry was used to analyze the extracted samples, which showed a broad scanning range of 215–1800 m/z. With MS-DIAL software and built-in LipidBlast database, we identified 38 lipids in positive, and 31 lipids in negative, ion mode, including lysophosphatidylcholine (lysoPC), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), etc. Then, the changes of lipids in BALF of mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS) was investigated, which may contribute to further exploration of the pathogenesis of ALI. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Banxia (BX) is the root of Pinellia ternata (Thunb.) Berit. Its processed products, such as Jiang Banxia (JBX), have been clinically used in traditional Chinese medicine to treat vomiting, coughing, and inflammation. However, data for their safety for pregnant women are contradictory and confusing. Aim of the study To further explore the safety of BX, an ultra-performance liquid chromatography coupled with liquid chromatography–mass spectrometry (LC–MS) and gas chromatography-mass spectrometry (GC–MS) metabolomics approach was used to evaluate the metabolic perturbation in pregnant rats caused by BX and JBX. Materials and methods Placenta and amniotic fluid samples were collected from control Sprague-Dawley pregnant rats and exposed to BX suspension and JBX decoction (1.434 g/kg/day). Samples were analyzed using LC–MS and GC–MS. The acquired MS data of above samples were further subjected to multivariate data analysis, and the significantly altered metabolites were identified. The associated pathways were constructed using MetaboAnalyst 3.0. Results The weight and histopathology of the placenta from each group of rats had no definite difference. However, we found 20 differential endogenous metabolites that changed significantly in the placenta and amniotic fluid samples. The alterations of identified metabolites indicated a perturbation in glycerophospholipid metabolism, amino acid metabolism, and carbohydrate metabolism in pregnant rats exposed to BX and JBX. Conclusion In summary, this work suggested that oral administration of BX and JBX may induce disturbances in the intermediary metabolism in pregnant rats. This work contributes to further understanding the safety of BX and its processed products. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Jiegeng (Radix Platycodi), the dried root of Platycodon grandiflorum A. DC (Campanulaceae), has been used to treat cough, sore throat, bronchitis, and bronchial asthma for thousands of years. It is commonly prescribed with Gancao (Radix et Rhizoma Glycyrrhizae ) as a herbal combination in traditional Chinese medicine (TCM) to produce synergistic effects. Aim of the study To elucidate the herbaceous compatibility of Jiegeng and Gancao, we investigated the comparative pharmacokinetics, intestinal absorption, and microbial metabolism of platycodin D (PD) and deapio-platycodin D (DPD), the platycodins contained in Jiegeng. Materials and methods In the comparative pharmacokinetic study, the concentrations of PD and DPD in Jiegeng extract (JE) and the Jiegeng–Gancao herb pair (JGHP) were determined in rat plasma using liquid chromatography–tandem mass spectrometry (LC–MS/MS). In addition, the main pharmacokinetic parameters were calculated using data analysis software (DAS). Furthermore, in vitro studies using Caco-2 cells and fecal lysates were performed to contradistinguish the intestinal absorption and microbial metabolism of PD and DPD in JE from those in JGHP. Results The peak concentration ( C max ) and area under the plasma concentration curve ( AUC ) of PD in rats orally administrated JGHP significantly increased compared to that in rats treated with JE. In addition, the time to reach peak concentration ( T max ) and half-life ( t 1/2 ) of PD and DPD in combination with JGHP were all prolonged compared with those of JE. There was no significant difference in the absorption of PD between JE and JGHP in Caco-2 cells. However, the hydrolysis of both PD and DPD in JGHP were weaker than that in JE after a 2-h incubation in fecal lysate which might be responsible for the different pharmacokinetic profiles of the platycodins in JE and JGHP. Conclusion In this study, we discovered that Gancao might influence the pharmacokinetic profiles of PD and DPD in Jiegeng. Furthermore, the difference in profiles may be attributable to the inequable microbial metabolism rather than intestinal absorption of the platycodins in JE and JGHP. The results of this study elucidated the pharmacokinetic compatibility and rationale for the use of JGHP. [ABSTRACT FROM AUTHOR]

• A repeatable GC–MS/MS method was developed for cellular targeted quantification of key metabolites in the TCA cycle and glycolysis. • Activated carbon was used for the purpose to obtain the analyte-free surrogate matrices in cells. • The optimized method was successfully applied to quantify and compare these targeted metabolites in three kinds of common hepatic cells. Energy synthesis in aerobic organisms relies on two major metabolic pathways, i.e. tricarboxylic acid (TCA) cycle and glycolysis, the metabolites of which are highly affected by many diseases. Cells are the basic unit of the organism and have independent, ordered and self-controlled metabolic systems. Therefore, it is necessary to quantify intracellular metabolites in TCA cycle and glycolysis. In this study, we established a repeatable gas chromatography-tandem mass spectrometry (GC–MS/MS) method with selected reaction monitoring (SRM) mode for simultaneous quantification of several primary metabolites in these two pathways, including glucose, 3-phosphoglycerate, phosphoenolpyruvate (PEP), pyruvate, lactate, citrate, cis-aconitate, isocitrate, α-ketoglutarate, succinate, fumarate and malate. There are many solvents to extract the metabolites in these two pathways, however, which one is more effective still remains unclear. Sample pretreatment was optimized for solvent types and volumes to advance the extraction efficiency of metabolites. 500 μL of 75% methanol-methyl tert-butyl ether (MTBE) was finally selected for the extraction of targeted metabolites in cells due to its highest extraction efficiency. Activated carbon as an effective adsorbent was successfully applied to the removal of endogenous targeted metabolites in cells for getting the analyte-free surrogate matrices. A series of methodological studies verified the validity of this optimized approach which was applied to quantify and compare the targeted metabolites in three common hepatic cells. The developed GC–MS/MS method provided a better way to determine the metabolites of energy metabolism in cellular metabolomics, facilitating the application of targeted quantification metabolomics to precisely discover the metabolic alterations. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Banxia (BX) is the dried tuber of Pinellia ternata (Thunb.) Breit., a commonly prescribed Chinese medicinal herb for the treatment of cough, phlegm, and vomiting in pregnant women. However, raw BX has been demonstrated to exert toxic effects on reproduction and the precise and comprehensive mechanisms remain elusive. Aim of the study We applied an iTRAQ (isobaric tags for relative and absolute quantitation, iTRAQ)-based proteomic method to explore the mechanisms of raw BX-induced fetal toxicity in mice. Materials and methods The mice were separated into two groups, control mice and BX-treated mice. From gestation days 6–8, the control group was treated with normal saline and the BX group was exposed to BX suspension (2.275 g/kg/day). Gastrulae were obtained and analyzed using the quantitative proteomic approach of iTRAQ coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS). A multi-omics data analysis tool, OmicsBean ( http://www.omicsbean.cn ), was employed to conduct bioinformatic analysis of differentially abundant proteins (DAPs). Quantitative real-time PCR (qRT-PCR) and western blotting methods were applied to detect the protein expression levels and validate the quality of the proteomics. Results A total of 1245 proteins were identified with < 1% false discovery rate (FDR) and 583 protein abundance changes were confidently assessed. Moreover, 153 proteins identified in BX-treated samples showed significant differences in abundance. Bioinformatics analysis showed that the functions of 37 DAPs were predominantly related to nervous system development. The expression levels of the selected proteins for quantification by qRT-PCR or western blotting were consistent with the results in iTRAQ-labeled proteomics data. Conclusion The results suggested that oral administration of BX in mice may cause fetal abnormality of the nervous system. The findings may be helpful to elucidate the underlying mechanisms of BX-induced embryotoxicity. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a common pathogen that causes lower respiratory tract disease in infants and the elderly, and no vaccination is presently available. Qingfei oral liquid (QF), a traditional Chinese medicine formula, has been shown in clinic to have anti-inflammatory properties. The present study investigated whether QF can suppress RSV-induced lung inflammation in mice models via fatty acid-dependent macrophage polarization. BALB/c mice were given a low, medium, or high dose of QF intragastrically for four consecutive days following RSV infection. The lung inflammatory status was assessed using H&E staining and cytokine assays. The active components of QF and fatty acid metabolism were analyzed using ultra-high-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). A lipid metabolism-related pathway was found through network pharmacology and molecular docking investigations. Western blotting assays were used to determine the levels of ATP-citrate lyase (ACLY), peroxisome proliferation-activated receptor alpha (PPAR), Akt protein kinase B and its phosphorylated form in Akt signaling. Flow cytometry was used to quantify the number of macrophage subtypes (M1/M2), and immunohistochemistry was used to examine the expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1). In the lung tissues of RSV-infected mice, QF suppressed the transcription of pro-inflammatory proteins such as interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6), while increasing the level of anti-inflammatory factors such as interleukin-10 (IL-10). The alterations in metabolic enzyme activity mediated by Akt signaling were linked to QF's significant reduction in lung fatty acid accumulation. Lower ACLY expression and higher PPAR expression were found after QF treatment, showing that these two enzymes were downstream targets of Akt signaling, controlling fatty acid synthesis (FAS) and fatty acid oxidation (FAO), respectively. The reprogramming of fatty acid metabolism resulted in the polarization of macrophages from M1 to M2, with lower expression of iNOS and higher expression of Arg-1. Additionally, application of an Akt agonist (SC-79) reduced QF's anti-inflammatory effects by increasing FAS and decreasing macrophage polarization. QF inhibited Akt-mediated FAS and polarized M1 to M2 macrophages, resulting in an anti-inflammatory impact. [Display omitted] • QF alleviated lung inflammation. • QF regulated fatty acid metabolism by Akt pathway. • QF induced M1 to M2 macrophage polarization. [ABSTRACT FROM AUTHOR]

Although pharmacokinetic alternations by hepatic injury have been extensively studied, little is known about the potential influence of hepatoprotective agent''s treatment. This study was aimed to investigate the holistic pharmacokinetics of multiple lignans, CYP3A regulations, and their correlations with hepatic injury biomarkers, in hepatic injured rats pretreated with or without schisandra lignan extract (SLE) and dimethyl-diphenyl-bicarboxylate (DDB). Integral pharmacokinetics of multiple lignans based on an AUC-weighting approach was determined in normal, CCl4 induced hepatic injury rats pretreated with or without SLE and DDB. Protein expression and activities of CYP3A were determined. Pharmacokinetic parameters and CYP3A activities were correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. CCl4 induced acute hepatic injury resulted in a nearly 8-fold enhancement of integral plasma exposures of multiple lignans, which was caused by the significant down-regulation of CYP3A. SLE and DDB pretreatment exhibited potent hepatoprotective effects, accompanied with the restored expression and activity of CYP3A, and the recovery of the respective and integral pharmacokinetics of lignans components. The integral AUC0–tn and CYP3A activities correlated well with ALT and AST. This study suggested that the pharmacokinetic regulating effects of hepatoprotective agent''s on themselves and co-prescribed drugs should be of concern, and hepatic injury biomarkers may serve as good predictors. [Copyright &y& Elsevier]

Accumulated evidences suggest that cardiolipins (CLs) and cardiolipin oxidation products (oxCLs) are a class of essential molecules that play critical roles in many physiological functions. Diversity of four acyl chains leads to high structure complexity for cardiolipin species including CLs, monolysocardiolipins (MLCLs) and their oxCLs. The ability to rapidly identify CL species can be implemented by the match of mass spectrometry (MS)-based in-silico spectral database. In this study, after optimizing the chromatography conditions and MS detection, an in-silico library containing 377,754 simulated tandem mass spectra deducing from 31,578 CLs to 52,160 of MLCLs was successfully augmented based on LipidBlast templates. For the construction of the oxCLs' library, twenty-five fatty acyls oxidation products relating to nine oxidation types were permuted and combined. A total of 42,180 oxCL spectra were predicted based on the experimental measurements of oxCLs forming by artificially oxidation. Applying the in-silico database to murine mitochondria and cell samples enabled the sensitive and comprehensive annotation of 86 MLCLs, 307 CLs and 112 oxCLs with high annotation confidence. Compared to the conventional method, our proposed in-silico database provides a more comprehensive interpretation for CL species' characterization with high throughput and sensitivity in nontarget lipidomic study. [Display omitted] • The method significantly improves the sensitivity of cardiolipin detection. • 31,578 cardiolipin spectra and 52,160 monolysocardiolipin spectra are augmented. • 4167 cardiolipin oxidations' molecules and 42,180 relating spectra are simulated. • Detection of CL species is successfully implemented in biological samples. [ABSTRACT FROM AUTHOR]