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An UHPLC-ESI-Q Exactive HF MS-based lipidomics method was successfully applied to profile various lipids from the plasma and lungs of mice intranasally challenged with lipopolysaccaride (LPS). Response trends of lipids to LPS were graphically represented by variable importance in projection (VIP) plot, heat map, and bar plot. As a result, 77 differential lipids in the lung and 13 differential lipids in the plasma were identified by comparison between healthy and LPS- induced mice. These results revealed the correlation between inflammation and lipids metabolism. The differentially regulated lipids could also be potentially used as biomarkers for inflammation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The use of Chinese medicines (CMs) during pregnancy has long been a major public health concern. Although CMs have been shown to be effective in treating infertility and preventing miscarriage, their use has been restricted, mainly because of limited knowledge of their potential toxicity. Accurate toxicology data are urgently required to assess whether these CMs are safe for maternal health and fetal development. Amniotic fluid (AF) contains carbohydrates, lipids and phospholipids, urea and proteins, all of which aid in the growth of the fetus and reflect the mother's health status as well. The changes in metabolomic patterns of AF are related to pathophysiological occurrences during the course of pregnancy. In this review, we provide a summary of the research performed in recent years on metabolomic AF samples, and use our previous study as an example to explore the feasibility of metabolomics of AF to evaluate the safety of CMs during pregnancy. We believe that metabolomics of AF play a far more important role than traditional morphology methods in the safety evaluation of CMs for pregnancy, with a higher sensitivity and correlation., (© 2018 John Wiley & Sons, Ltd.)

Introduction: Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring in the first 3 months of life. The most common causes of neonatal cholestasis are infantile hepatitis syndrome (IHS) and biliary atresia (BA). The clinical manifestations of the two diseases are too similar to distinguish them. However, early detection is very important in improving the clinical outcome of BA. Currently, a liver biopsy is the only proven and effective method used to differentially diagnose these two similar diseases in the clinic. However, this method is invasive. Therefore, sensitive and non-invasive biomarkers are needed to effectively differentiate between BA and IHS. We hypothesized that urinary metabolomics can produce unique metabolite profiles for BA and IHS., Objectives: The aim of this study was to characterize urinary metabolomic profiles in infants with BA and IHS, and to identify differences among infants with BA, IHS, and normal controls (NC)., Methods: Urine samples along with patient characteristics were obtained from 25 BA, 38 IHS, and 38 NC infants. A non-targeted gas chromatography-mass spectrometry (GC-MS) metabolomics method was used in conjunction with orthogonal partial least squares discriminant analysis (OPLS-DA) to explore the metabolomic profiles of BA, IHS, and NC infants., Results: In total, 41 differentially expressed metabolites between BA vs. NC, IHS vs. NC, and BA vs. IHS were identified. N-acetyl-D-mannosamine and alpha-aminoadipic acid were found to be highly accurate at distinguishing between BA and IHS., Conclusions: BA and IHS infants have specific urinary metabolomic profiles. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be used to discriminate BA from IHS.

Human cytomegalovirus (HCMV) infection in infants is a global problem and the liver is a target organ of HCMV invasion. However, the mechanism by which HCMV causes different types of liver injury is unclear, and there are many difficulties in the differential diagnosis of HCMV infantile cholestatic hepatopathy (ICH) and extrahepatic biliary atresia (EHBA). We established a non-targeted gas chromatography-mass spectrometry metabolomics method in conjunction with orthogonal partial least squares-discriminate analysis based on 127 plasma samples from healthy controls, and patients with HCMV infantile hepatitis, HCMV ICH, and HCMV EHBA to explore the metabolite profile of different types of HCMV-induced liver injury. Twenty-nine metabolites related to multiple amino acid metabolism disorder, nitrogen metabolism and energy metabolism were identified. Carbamic acid, glutamate, L-aspartic acid, L-homoserine, and noradrenaline for HCMV ICH vs. HCMV EHBA were screened as potential biomarkers and showed excellent discriminant performance. These results not only revealed the potential pathogenesis of HCMV-induced liver injury, but also provided a feasible diagnostic tool for distinguishing EHBA from ICH.

Objective To analyze urinary metabolites of bronchial asthma children patients with phlegm-heat obstructing Fei syndrome (PHOFS) and non-PHOFS using gas chromatography-mass spec- trometry/mass spectrometer ( GC-MS/MS) , thus performing research on syndrome markers. Methods Totally 44 bronchial asthma children patients with PHOFS and non-PHOFS in onset of asthma were recrui- ted. Another 29 healthy children were also recruited. Their urine samples were analyzed by GC-MS/MS. The profiles were analyzed using orthogonal partial least squares-discriminant analysis (OPLS-DA) , vari- able importance in the projection (VIP) , and non-parametric test to determine intergroup differential metabolites. Abnormal metabolic pathways were determined by Metaboanalyst. Results Compared with the health control group, contents of fourteen substances like inositol, uric acid, stearic acid, and so on de- creased, and mino-malonic acid content increased in asthma episode children (P <0. 05). The process was mainly involved in 5 metabolic pathways such as lysine degradation and biosynthesis, pyruvate me- tabolism, and so on. Compared with the non-PHOFS group in bronchial asthma episode, contents of nine substances like oxalic acid, L-threonine, pyrimidine, and so on decreased in the PHOFS group (P < 0. 05). The process was mainly involved in 5 metabolic pathways such as pentose phosphate pathway, inositol phosphate metabolism, and so on. Conclusions Urinary metabolites are different in infantile bronchial asthma episode and healthy children. Metabolic biomarkers and pathways exist in different syn- dromes in bronchial asthma episode.

Lipid metabolic pathways play pivotal roles in liver function, and disturbances of these pathways are associated with various diseases. Thus, comprehensive characterization and measurement of lipid metabolites are essential to deciphering the contributions of lipid network metabolism to diseases or its responses to drug intervention. Here, we report an integrated lipidomic analysis for the comprehensive detection of lipid metabolites. To facilitate the characterization of untargeted lipids through fragmentation analysis, nine formulas were proposed to identify the fatty acid composition of lipids from complex MS (n) spectrum information. By these formulas, the co-eluted isomeric compounds could be distinguished. In total, 250 lipids were detected and characterized, including diacylglycerols, triacylglycerols, glycerophosphoethanolamines, glycerophosphocholines, glycerophosphoserines, glycerophosphoglycerols, glycerophosphoinositols, cardiolipins, ceramides, and sphingomyelins. Integrated with the targeted lipidomics, a total of 27 inflammatory oxylipins were also measured. To evaluate the aberrant lipid metabolism involved in liver injury induced by Tripterygium wilfordii, lipid network metabolism was further investigated. Results indicated that energy lipid modification, membrane remodeling, potential signaling lipid alterations, and abnormal inflammation response were associated with injury. Because of the important roles of lipids in liver metabolism, this new method is expected to be useful in analyzing other lipid metabolism diseases.

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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Acute lung injury (ALI), an acute inflammatory lung disease, can cause a rapid inflammatory response in clinic, which endangers the patient's life. The components of platycodon grandiflorum, such as platycodins have a wide range of pharmacological activities such as expectorant, anti-apoptotic, anti-inflammatory, anti-tumor and anti-oxidant properties, and can be used for improving human immunity. Previous studies have shown that aqueous extract of platycodon grandiflorum (PAE) has a certain protective effect on ALI, but the main pharmacodynamic components and the mechanism of action are not clear. Methods: The anti-inflammatory properties of PAE were studied using the lipopolysaccharide (LPS)-induced ALI animal model. Hematoxylin and eosin stains were used to assess the degree of acute lung damage. Changes in RNA levels of pro-inflammatory cytokines in the lungs were measured using quantitative RT-qPCR. The potential molecular mechanism of PAE preventing ALI was predicted by lipidomics and network pharmacology. To examine the anti-apoptotic effects of PAE, TdT-mediated dUTP nick-end labelling (TUNEL) was employed to determine apoptosis-related variables. The amounts of critical pathway proteins and apoptosis-related proteins were measured using Western blotting. Results: Twenty-six chemical components from the PAE were identified, and their related pathways were obtained by the network pharmacology. Combined with the analysis of network pharmacology and literature, it was found that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is related to ALI. The results of lipidomics show that PAE alleviates ALI via regulating lung lipids especially phosphatidylinositol (PI). Finally, the methods of molecular biology were used to verify the mechanism of PAE. It can be found that PAE attenuates the inflammatory response to ALI by inhibiting apoptosis through PI3K/Akt signaling pathway. Conclusion: The study revealed that the PAE attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling. Furthermore, our findings provide a novel strategy for the application of PAE as a potential agent for preventing patients with ALI. [ABSTRACT FROM AUTHOR]

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]

Rheumatoid arthritis (RA) is a global disease with a high disability rate. Moxibustion, a well-known traditional Chinese medicine (TCM) therapy that has a long history in the treatment of RA, has attracted increasing clinical attention. However, little is known about its therapeutic mechanism. This study aimed to investigate the mechanism of moxibustion in the treatment of RA in rats through metabolomics. In this study, rats with collagen-induced arthritis (CIA) were treated with moxibustion daily for three weeks at the Shenshu (BL 23) and the Zusanli acupoints (ST 36). Their weight, swelling of the hind paw, arthritic scores, histopathological parameters, and inflammatory factors were assessed. The urine samples of the rats in each group were collected after each course of moxibustion treatment. Gas chromatography–mass spectrometry was used to explore the changes in the urine metabolism spectrum at different courses of moxibustion treatment and analyze the relevant targeted metabolic pathways. Results showed that moxibustion alleviated the severity of arthritis and changed 33 metabolites in the urine of rats. These metabolites are involved in glycolysis/gluconeogenesis; tricarboxylic acid (TCA) cycle; and phenylalanine, tryptophan, butanoate, and purine metabolism. The levels of these metabolites in the moxibustion group showed trends similar to those in the control group. Moxibustion treatment effectively inhibited inflammation in rats with CIA by regulating glycolysis/gluconeogenesis; TCA cycle; phenylalanine, tryptophan, purine and butanoate metabolism; and other biological pathways. Metabolomics may be an effective way to explain the mechanisms of moxibustion for RA. [ABSTRACT FROM AUTHOR]

Pyrexia is considered as a part of host's defense response to the invasion of microorganisms or inanimate matter recognized as pathogenic or alien, which frequently occurs in children. Jinxin oral liquid (JXOL) is a traditional Chinese medicine formula that has been widely used to treat febrile children in China. Experimental fever was induced by injecting yeast into young male Sprague-Dawley rats (80 ± 20 g) and the rectal temperature subsequently changed. Four hours later, the excessive production of interleukin (IL)-1β and prostaglandin (PG) E2 induced by yeast was regulated to normal by JXOL administration. A rat brain metabolomics investigation of pyrexia of yeast and antipyretic effect of JXOL was performed using gas chromatography-mass spectrometry (GC-MS). Clear separation was achieved between the model and normal group. Twenty-two significantly altered metabolites were found in pyretic rats as potential biomarkers of fever. Twelve metabolites, significantly adjusted by JXOL to help relieve pyrexia, were selected out as biomarkers of antipyretic mechanism of JXOL, which were involved in glycolysis, purine metabolism, tryptophan mechanism, etc. In conclusion, the brain metabolomics revealed potential biomarkers in the JXOL antipyretic process and the associated pathways, which may aid in advanced understanding of fever and therapeutic mechanism of JXOL. [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]

This study aimed to investigate how maternal asthma during pregnancy disrupts fetal lung development by altering lipid metabolism in the amniotic fluid, which is crucial for fetal development. A pregnancy-induced asthma model was established in female rats using house dust mite (HDM) as a common allergen. The fetuses were divided into four groups based on whether the mother and fetus were exposed to the allergen: PBS+PBS, PBS+HDM, HDM+PBS, and HDM+HDM. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to analyze changes in the lipid profile of the amniotic fluid and bronchoalveolar lavage fluid (BALF). Principal component analysis (PCA) and ChemRICH methods were used to explore the potential relationship between lipid metabolism abnormalities and impaired fetal lung development. The results indicate that maternal asthma exacerbates asthma-related inflammatory markers in fetuses, leading to pathological changes in the lungs and elevated levels of cytokines IL-5, IL-13, and IgE. Additionally, 18 differential lipids, primarily oxygenated lipids, were identified in the amniotic fluid after modeling, suggesting an enhanced oxidative stress environment for the fetus. This environment causes metabolic disturbances in various lipid groups in fetal lungs, with the HDM+HDM group showing significant abnormalities in lipids critical for lung development, including phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and fatty acids (FA). In conclusion, gestational asthma can reshape the lipid profile in the amniotic fluid and BALF, significantly disrupting fetal growth and lung development. Restoring normal lipid metabolism in the amniotic fluid and fetal lungs may offer a potential therapeutic approach to managing aberrant fetal lung development in asthmatic mothers. [Display omitted] • LC-MS studies asthma's impact on lipid metabolism in amniotic fluid and fetal lavage fluid. • Uncontrolled asthma disrupts lipid metabolism, explaining fetal lung function decline. • Maternal asthma increases fetal airway sensitivity, causing severe lung development deficits. • Study highlights asthma effects, offers innovative approach for future metabolite research. [ABSTRACT FROM AUTHOR]

Panacis Quinquefolii Radix (PQR) is often illegally sulfur fumigated to extend shelf life and improve appearance, but existing regulations of detecting SO 2 residues do not accurately identify desulfurized sulfur-fumigated PQR (SF-PQR). Although sulfur-containing derivatives (SCDs) have been reported in some sulfur-fumigated herbs, there is a lack of research on the generation mechanisms and toxicity of SCDs. Our previous study reported the nephrotoxicity of SF-PQR, and there is an urgent necessity to illuminate the mechanism of toxicity as well as its association with SCDs. To investigate the transformation pattern of chemical components and SCDs in SF-PQR, and to disclose the linkage between SCDs and SF-PQR nephrotoxicity. The extracts of PQR (before and after SF) were detected by the UPLC-LTQ-Orbitrap-MS method, and SCDs were screened as quality markers (Q-markers). The composition of sulfur combustion products was examined by ion chromatography to exploit the conversion mechanism of SCDs. After administration of PQR extracts to mice for two weeks, serum was collected for GC-MS-based untargeted metabolomics study to mine for differential metabolites. The upstream genes were traced by network analysis to probe toxicity targets. Molecular docking was used to uncover the interactions between SCDs and the targets. Thirty-three compounds were identified and 11 SCDs of saponins were screened, including four SO 3 sulfonation products and five H 2 SO 3 sulfonation products. Metabolomics study showed significant alterations in serum biochemistry of SF-PQR group, with substantial increases in fumarate and 2-heptanone content, and induced disturbances in glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis in mice. Network analysis revealed that the key toxicity targets were DECR1, PLA2G1B, and CAT. Molecular docking indicated that SCDs had stable interaction forces with the above three toxicity targets. SF-PQR caused kidney damage by affecting glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. Eleven SCDs were potential nephrotoxic substances and Q-markers for identifying SF-PQR. This study is the first to systematically elucidate the mechanism of SF-PQR-related nephrotoxicity, providing a robust basis for the construction of new quality control standards and a global prohibition of sulfur fumigation. [Display omitted] • Sulfur-fumigated Panacis Quinquefolii Radix (SF-PQR) is known to cause renal damage. • Eleven sulfur-containing derivatives (SCDs) can be Q-markers of identifying SF-PQR. • Five new SCDs were identified as sulfonation products with H 2 SO 3. • SF-PQR disrupted Glycerolipid metabolism and Phenylalanine biosynthesis in mice. • SCDs are toxicants of SF-PQR-related nephrotoxicity. [ABSTRACT FROM AUTHOR]

Flos Lonicerae Japonica-Fructus Forsythiae herb pair ( Yin-Qiao in Chinese, YQ), is used clinically for the treatment of viral pneumonia due to its heat-clearing and detoxifying functions. In the present work, the effect of YQ in H1N1-induced inflammation in mice was investigated by metabolomics based on GC–MS. Body weight and histological results were used to assess the lung injury, while the levels of IL-6 and TNF-α in plasma were used to evaluate the extent of inflammation. The acquired GC–MS data were further subjected to multivariate data analysis, and the significantly altered metabolites identified. After statistical and pathway analysis, 17 significantly altered metabolites and 3 possible metabolic pathways were found in plasma between normal and H1N1-induced pneumonia mice, while 17 significant differential metabolites were identified when YQ treatment group was compared with model group. This work indicates that oral administration of YQ could protect mice from H1N1-induced inflammation partially by ameliorating the associated metabolic disturbances. [ABSTRACT FROM AUTHOR]

• Effective quantitative evaluation method for the efficacy of TCM with targeted cellular metabolomics. • Highly correlation between senescence and two energy metabolic pathways, TCA cycle and glycolysis. • Successful application to the efficacy evaluation of EZW and screen of effective extracts. The complexity of ingredients in traditional Chinese medicine (TCM) makes it challenging to clarify its efficacy in an acceptable and scientific approach. The present study was aimed to use quantification results from targeted cellular metabolomics to evaluate anti-aging efficacy of a famous Chinese medicine formula, Erzhi Wan (EZW), and screen possible effective extracts, depending on the developed strategy integrating multivariate receiver operating characteristic (ROC) curve and analytic hierarchy process (AHP). In this study, senescent NRK cells induced by D-galactose were treated with drug-containing serum of EZW and four kinds of extracts (petroleum ether, ethyl acetate, butanol and water). Intermediates of two major metabolic pathways for energy synthesis, tricarboxylic acid (TCA) cycle and glycolysis, were accurately quantified by GC–MS/MS to identify discriminate metabolites for clarifying therapeutic mechanism of EZW based on multivariate statistical analysis. Senescent and non-senescent cells were successfully distinguished using these metabolites by ROC curve analysis. Next, these metabolites were used as evaluation indexes to quantitatively reflect different effect of EZW and its extracts, according to the role of them in distinguishing groups and in conjunction with AHP. In vitro detection of senescence-associated β-galactosidase (SA-β-gal) activity was used to verify the reliability of evaluation results. The reversal after treatment of drug-containing serum of EZW and extracts was observed, and the petroleum ether extract might be the potential active extract responsible for the major anti-aging effect of EZW, which was in agreement with in vitro experiments. Altogether, metabolomics was a powerful approach for evaluation efficacy and elucidation action mechanisms of TCM. The integrated evaluation strategy in this paper with properties of high practicality, feasibility and effectivity was expected to provide a new insight into comprehensive and quantitative efficacy evaluation. [ABSTRACT FROM AUTHOR]