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Modified Tabusen-2 decoction (MTBD) is traditional Chinese Mongolia medicine, mainly used to treat osteoporosis. However, the precise material basis of this prescription is not yet fully elucidated. Herein, we establish an HPLC-Q-Exactive MS/MS spectrometer method with four-step characteristic ion filtering (FSCIF) strategy to quickly and effectively identify the structural features of MTBD and determine the representative compounds content. The FSCIF strategy included database establishment, characteristic ions summarization, neutral loss fragments screening, and secondary mass spectrum fragment matching four steps. By using this strategy, a total of 143 compounds were unambiguously or tentatively annotated, including 5 compounds which were first reported in MTBD. Nineteen representative components were simultaneously quantified with the HPLC-Q-Exactive MS/MS spectrometer, and it is suitable for eight batches of MTBD. Methodology analysis showed that the assay method had good repeatability, accuracy, and stability. The method established above was successfully applied to assess the quality of MTBD extracts. Collectively, our findings enhance our molecular understanding of the MTBD formulation and will allow us to control its quality in a better way. At the same time, this study can promote the development and utilization of ethnic medicine. [ABSTRACT FROM AUTHOR]

The secondary structure content of proteins and their complexes may change significantly on passing from aqueous solution to the gas phase (as in mass spectrometry experiments). In this work, we investigate the impact of hydrophobic residues on the formation of the secondary structure of a real protein complex in the gas phase. We focus on a well-studied protein complex, the amyloid-β (1-40) dimer (2Aβ). Molecular dynamics simulations reproduce the results of ion mobility-mass spectrometry experiments. In addition, a helix (not present in the solution) is identified involving 19FFAED23, consistent with infrared spectroscopy data on an Aβ segment. Our simulations further point to the role of hydrophobic residues in the formation of helical motifs – hydrophobic sidechains “shield” helices from being approached by residues that carry hydrogen bond sites. In particular, two hydrophobic phenylalanine residues, F19 and F20, play an important role for the helix, which is induced in the gas phase in spite of the presence of two carboxyl-containing residues. [ABSTRACT FROM AUTHOR]

Alternating current (AC) electrolysis is an emerging field in synthetic chemistry, however its mechanistic studies are challenged by the effective characterization of the elusive intermediate processes. Herein, we develop an operando electrochemical mass spectrometry platform that allows time‐resolved mapping of stepwise electrosynthetic reactive intermediates in both direct current and alternating current modes. By dissecting the key intermediate processes of electrochemical functionalization of arylamines, the unique reactivities of AC electrosynthesis, including minimizing the over‐oxidation/reduction through the inverse process, and enabling effective reaction of short‐lived intermediates generated by oxidation and reduction in paired electrolysis, were evidenced and verified. Notably, the controlled kinetics of reactive N‐centered radical intermediates in multistep sequential AC electrosynthesis to minimize the competing reactions was discovered. Overall, this work provides direct evidence for the mechanism of AC electrolysis, and clarifies the underlying reasons for its high efficiency, which will benefit the rational design of AC electrosynthetic reactions. [ABSTRACT FROM AUTHOR]

Alternating current (AC) electrolysis is an emerging field in synthetic chemistry, however its mechanistic studies are challenged by the effective characterization of the elusive intermediate processes. Herein, we develop an operando electrochemical mass spectrometry platform that allows time‐resolved mapping of stepwise electrosynthetic reactive intermediates in both direct current and alternating current modes. By dissecting the key intermediate processes of electrochemical functionalization of arylamines, the unique reactivities of AC electrosynthesis, including minimizing the over‐oxidation/reduction through the inverse process, and enabling effective reaction of short‐lived intermediates generated by oxidation and reduction in paired electrolysis, were evidenced and verified. Notably, the controlled kinetics of reactive N‐centered radical intermediates in multistep sequential AC electrosynthesis to minimize the competing reactions was discovered. Overall, this work provides direct evidence for the mechanism of AC electrolysis, and clarifies the underlying reasons for its high efficiency, which will benefit the rational design of AC electrosynthetic reactions. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicines (TCMs) are gaining more and more attentions all over the world. The focus of TCMs researches were gradually shifted from chemical research to the combination study of chemical and life sciences. However, obtaining precise information of TCMs process in vivo or in vitro is still a bottleneck in bioanalysis of TCMs for their chemical composition complexity. This paper reviewed the recent analytical methods especially mass spectrometry technology in the bioanalysis of TCMs, and data processing techniques in the qualitative and quantitative analyses of metabolite of TCMs. Additionally, the difficulties encountered in the analyzing biological samples in TCMs and the solutions to these problems have been mentioned. [ABSTRACT FROM AUTHOR]

Asiatic acid (1) is a natural triterpenoid isolated fromCentella asiatica. This paper reports the microbial transformation of asiatic acid by an endophytic fungusUmbelopsis isabellinato obtain derivatives potentially useful for further studies. Incubation of asiatic acid withU. isabellinaafforded two derivatives 2α,3β,7β, 23-tetrahydroxyurs-12-ene-28-oic acid (2) and 2α,3β,7β,23-tetrahydroxyurs-11-ene-28,13-lactone (3). The structures of these compounds were elucidated by spectral data. Compound3has formed an unusual lactone. These two products are new compounds. The possible transformation passway was also discussed. [ABSTRACT FROM PUBLISHER]

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]

Few studies have examined the relationship between lipid metabolism and kidney stone formation, particularly the role of key lipid regulatory factors in kidney stone formation. We evaluated the effect of the lipid regulatory factor‐peroxisome proliferator‐activated receptor alpha on the formation of renal stones in mice by injecting them with glyoxylate followed by treatment with either a peroxisome proliferator‐activated receptor alpha agonist fenofibrate or an antagonist GW6471 (GW). Liquid chromatography coupled with trapped ion mobility spectrometry‐quadrupole‐time‐of‐flight mass spectrometry‐based lipidomics was used to determine the lipid profile in the mouse kidneys. Histological and biochemical analyses showed that the mice injected with glyoxylate exhibited crystal precipitation and renal dysfunction. Crystallization decreased significantly in the fenofibrate group, whereas it increased significantly in the GW group. A total of 184 lipids, including fatty acyls, glycerolipids, glycerophospholipids, and sphingolipids differed significantly between the mice in the model and control groups. Peroxisome proliferator‐activated receptor alpha activity negatively correlated with glyoxylate‐induced kidney stone formation in mice, which may be related to improved fatty acid oxidation, maintenance of ceramide/complex sphingolipids cycle balance, and alleviation of disorder in phospholipid metabolism. [ABSTRACT FROM AUTHOR]

Attached to the outer surface of the corneocyte lipid envelope (CLE), omega-hydroxy ceramides (ω-OH-Cer) link to involucrin and function as lipid components of the stratum corneum (SC). The integrity of the skin barrier is highly dependent on the lipid components of SC, especially on ω-OH-Cer. Synthetic ω-OH-Cer supplementation has been utilized in clinical practice for epidermal barrier injury and related surgeries. However, the mechanism discussion and analyzing methods are not keeping pace with its clinical application. Though mass spectrometry (MS) is the primary choice for biomolecular analysis, method modifications for ω-OH-Cer identification are lacking in progress. Therefore, finding conclusions on ω-OH-Cer biological function, as well as on its identification, means it is vital to remind further researchers of how the following work should be done. This review summarizes the important role of ω-OH-Cer in epidermal barrier functions and the forming mechanism of ω-OH-Cer. Recent identification methods for ω-OH-Cer are also discussed, which could provide new inspirations for study on both ω-OH-Cer and skin care development. [ABSTRACT FROM AUTHOR]

Hypothyroidism is known to be closely associated with lipid metabolism. Although our previous serum and urine metabonomics studies have provided some clues about the molecular mechanism of hypothyroidism at the metabolic level, the precise mechanism underlying the pathogenesis of hypothyroidism remains elusive, especially from the aspect of lipid metabolism. In the present study, we applied an ultra high performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS)-based lipidomics method to analyze the global lipid profiles of hypothyroidism in rat cerebellum. Using unsupervised analysis and multivariate statistical analysis, we separated the Sham and hypothyroid groups clearly and screened out 23 potential lipid biomarkers related to hypothyroidism that were primarily involved in sphingolipid metabolism, glycerophospholipid metabolism and β-oxidation of fatty acid. Subsequently, we conducted computational analysis to build and simulate the lipid network of hypothyroidism, knowing that it would be useful to elucidate the pathological mechanism of hypothyroidism. Based on the selected 23 lipid biomarkers, we systematically evaluated the therapeutic effects of Sini decoction ( SND ) and the positive drug T 4 . The results showed that both SND and T 4 can to some extent convert the pathological status of hypothyroidism through different pathways. Overall, this investigation illustrates that lipidomic profiling approach is powerful in giving a complementary view to the pathophysiology of hypothyroidism and offers a valuable tool for systematic study of the therapeutic effects of SND on hypothyroidism at lipid level. [ABSTRACT FROM AUTHOR]

Abstract: An iridium(III) pyrimidine complex Ir(NDMP)2acac (NDMP = 2-(2-naphthyl)-4,6-dimethylpyrimidine, acac = acetylacetonate) was synthesized and characterized by 1H NMR, 13C NMR, MALDI-TOF mass spectrometry and elemental analysis. An unexpected mononuclear complex Ir(NDMP)2(Cl)(H2O) was obtained in the process of preparing the Cl-bridged dimer [Ir(NDMP)2Cl]2. The crystal structures of these complexes were determined by X-ray single crystal diffraction and contrastively studied. The photoluminescence spectrum of Ir(NDMP)2acac exhibits a yellow emission at 560nm. The HOMO and LUMO energy levels of Ir(NDMP)2acac were calculated to be −5.14eV and −2.80eV respectively. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence shows that circulating levels of trimethylamine N-oxide, which is generated from the metabolism of dietary choline, may predict cardiovascular disease among Caucasians. Acute coronary syndrome (ACS), one common presentation of cardiovascular disease, is a spectrum of signs and symptoms due to acute decreased blood flow in the coronary arteries. The relationship between the metabolites from choline pathway and ACS remains unclear. We aimed to assess the associations of circulating metabolites from the choline pathway with ACS among a Chinese population, who consume a different dietary pattern than their Western counterparts. Methods: We recruited 501 participants who were admitted to the Department of Cardiology, Zhongshan Hospital,Shanghai China between March 2017 and June 2018, including 254 ACS cases and 247 controls. Liquid chromatography-tandem mass spectrometry was used to measure circulating concentrations of metabolites in the choline pathway, including betaine, choline, trimethylamine, and trimethylamine N-oxide. A composite metabolite score using a weighted sum of these four metabolites, and the betaine/choline ratio were calculated. Multivariable logistic regressions were applied to estimate the association of metabolites with ACS, with adjustment of age, sex, body mass index, smoking index, history of diseases, and kidney function. Results: After adjusting for traditional risk factors, per 1-standard deviation (SD) increment in choline was positively associated with the odds of ACS [odds ratio (OR), 95% confidence interval (CI), 1.77(1.44–2.18)], and the other metabolites were not associated with ACS at a statistical significance level. Compared with participants in the lowest quartile of the metabolite score, those in the highest quartile had higher odds of ACS [OR (95% CI), 3.18(1.85–5.54), p < 0.001 for trend]. Per 1-SD increment in metabolite score was positively associated with higher odds of ACS [OR (95% CI), 1.80 (1.37–2.40)], and per 1-SD increment in the betaine/choline ratio was inversely associated with the odds of ACS [OR (95% CI), 0.49 (0.39–0.60)]. Conclusions: Among our Chinese participants, trimethylamine N-oxide was not associated with ACS, while a composite metabolite score of metabolites from the choline pathway was associated with increased odds of ACS. The choline pathway metabolites may be related to the pathophysiology of ACS among Chinese. [ABSTRACT FROM AUTHOR]

Three new (6, 9, and 12) and nine known steroidal saponins were obtained from the fermentation broth of pseudoprotodioscin (PPD) incubated with a fungus Gibberella fujikuroi CGMCC 3.4663. Structures of the metabolites were elucidated by 1-D (1H, 13C), 2-D (HMBC, HSQC, NOESY) NMR, and HR-MS analyses. The biotransformation pathway of pseudoprotodioscin by Gibberella fujikuroi CGMCC 3.4663 was proposed. Compounds 1-11 were tested in vitro for their cytotoxic activities against two human cancer cell lines (HepG2 and Hela). Compounds 1, 6, 9, and 10 exhibited cytotoxic activity against HepG2 cells. Compound 10 exhibited cytotoxicity to Hela cells. [ABSTRACT FROM AUTHOR]

Background & objectives: Acute rheumatic fever and rheumatic heart disease (RHD) are important public health problems in developing countries. In this study, peptidomic analyses on RHD patients and healthy individuals were performed to characterize variations in serum peptide levels using label-free quantitation approaches. Methods: Blood samples were obtained from 160 healthy controls and 160 RHD patients. Of the 448 identified peptides, 272 were analyzed by two label-free mass spectrometry methods, the spectral count and spectral index. Results: There were 38 proteins and 95 peptides with significant (adjusted P<0.001) differences in the abundance of peptides between healthy controls and RHD patients, including multiple peptides derived from histone H2B, villin-like protein, complement C4-B and motile sperm domain containing protein-2. The levels of 10 peptides were upregulated, and 85 peptides were downregulated in patients compared to controls. In addition, in patients, the levels of four proteins were upregulated and 34 were downregulated compared to controls. Interpretation & conclusions: This study shows that detection of significant changes in serum peptides reflects the difference between RHD patients and healthy controls. This label-free method may be helpful for clinicians to treat RHD patients during the perioperative period. [ABSTRACT FROM AUTHOR]

This study was designed to develop a simple, specific and reliable method to overall analyze the chemical constituents in clematidis radix et rhizome/notopterygii rhizome et radix herb couple using high-performance liquid chromatography coupled with tandem mass spectrometry and multiple chemometric analysis. First, the separation and qualitative analysis of herb couple was achieved on an Agilent Zorbax Eclipse Plus C18 column (250 mm × 4.6 mm, 5 μm), and 69 compounds were unambiguously or tentatively identified. Moreover, in quantitative analysis, eight ingredients including six coumarins and two triterpenoid sapogenins were quantified by high-performance liquid chromatography coupled with tandem mass spectrometry. In terms of good linearity ( r2 ≥ 0.9995) with a relatively wide concentration range, recovery (85.40-102.50%) and repeatability (0.99-4.45%), the validation results suggested the proposed method was reliable, and successfully used to analyze ten batches of herb couple samples. Then, hierarchical cluster analysis and principal component analysis were used to classify samples and search significant ingredients. The results showed that ten batches of herb couple samples were classified into three groups, and six compounds were found for its better quality control. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Herb pair serves as the basic building block of a traditional Chinese medicine (TCM) formula. The rhubarb–gardenia herb pair (RGHP), composed of rhubarb and gardenia, has meaningful clinical effects to cure cholestasis diseases. This study was designed to confirm the expected synergistic effects of RGHP at pharmacodynamic and pharmacokinetic levels. Materials and methods Thirty male Sprague-Dawley rats were divided into control, model and drug-treated groups. After intragastrically administrated with α -naphthylisothiocyanate (ANIT) to induce cholestasis, rats were treated with rhubarb, gardenia or RGHP. For pharmacodynamic study, biochemical and histopathological tests were performed to assess the hepatoprotective effects. While for pharmacokinetic study, a LC–MS method was developed for determination of five main chemical markers, namely genipin, rhein, aloe emodin, emodin and chrysophanol in rat plasma. Results The biochemical and histopathological tests suggested that RGHP exerted enhanced hepatoprotective effects against the ANIT-induced cholestasis compared with single herbs. The pharmacokinetic study indicated RGHP could significantly elevate systemic exposure level and prolong retention time of five markers in comparison with rhubarb or gardenia alone. Conclusions The present study demonstrated the synergistic effects of RGHP in ANIT-induced cholestatic rats at pharmacodynamic and pharmacokinetic levels, and has significant enlightenments for the rational use of the related TCM formulas containing RGHP. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Orthosiphon stamineus (OS), a traditional Chinese herb, is often used for promoting urination and treating nephrolithiasis. Aim of the study Urolithiasis is a major worldwide public health burden due to its high incidence of recurrence and damage to renal function. However, the etiology for urolithiasis is not well understood. Metabonomics, the systematic study of small molecule metabolites present in biological samples, has become a valid and powerful tool for understanding disease phenotypes. In this study, a urinary metabolic profiling analysis was performed in a mouse model of renal calcium oxalate crystal deposition to identify potential biomarkers for crystal-induced renal damage and the anti-crystal mechanism of OS. Materials and methods Thirty six mice were randomly divided into six groups including Saline, Crystal, Cystone and OS at dosages of 0.5 g/kg, 1 g/kg, and 2 g/kg. A metabonomics approach using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was developed to perform the urinary metabolic profiling analysis. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were utilized to identify differences between the metabolic profiles of mice in the saline control group and crystal group. Results Using partial least squares-discriminant analysis, 30 metabolites were identified as potential biomarkers of crystal-induced renal damage. Most of them were primarily involved in amino acid metabolism, taurine and hypotaurine metabolism, purine metabolism, and the citrate cycle (TCA). After the treatment with OS, the levels of 20 biomarkers had returned to the levels of the control samples. Conclusions Our results suggest that OS has a protective effect for mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways primarily involving amino acid, energy and choline metabolism. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: To investigate the synergistic property of Platycodonis Radix (PG) in a classic Traditional Chinese Medicine (TCM) prescription Shengxian Decoction (SXT) by combining chemical profile with pharmacokinetic analysis strategy. The synergized prescription consisted of Astragali Radix, Anemarrhenae Rhizoma, Bupleuri Radix, and Cimicifuage Rhizoma. Materials and methods: Ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry (UPLC–Q-TOF/MS) was employed to investigate the chemical fingerprints of SXT and decreased SXT (SXT that removed Platycodonis Radix, SXT-PG). A reliable LC–MS/MS method was developed to examine the pharmacokinetics of 9 marker compounds (including formononetin, calycosin-7-O-β-d-glucoside, ononin, caffeic acid, isoferulic acid, mangiferin, timosaponin E1, timosaponin B-II and timosaponin B) following oral administration of SXT and SXT-PG in rats. Both in vitro chemical profiles and in vivo pharmacokinetic parameters differences between SXT and SXT-PG were conducted. Results: By using UPLC–Q-TOF/MS method, a total of 25 compounds identified from SXT, including 13 triterpenoids, 5 caffeinic derivatives, 4 isoflavonoids and 3 xanthone glycosides. Comparing the chemical fingerprints between SXT and decreased SXT did not reveal significant difference in the chemical profile of other four TCMs. The improved pharmacokinetic profiles of mangiferin, timosaponin E1, timosaponin B-II and timosaponin B were found in SXT group, suggesting the quicker distribution and more effective absorption, when compared with those in the SXT-PG group. Conclusions: These results indicated that PG did not increase the dissolution of synergized prescription when co-decocting, but guided the synergized prescription to target location, reflecting the courier role of PG, which was in line with the clinical principle of TCM. It also established a useful method for TCM synergistic property research. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The lateral root of Aconitum has been popularly used in traditional Chinese medicine (TMC) known as Fuzi which is beneficial for the treatment of various diseases, such as rheumatism, painful joints, syncope and bronchial asthma. However, it has a potential carditoxicity with a relatively narrow margin of safety. Aim of the study: This paper was designed to explore the mechanisms of Fuzi's toxicity and find out potential tissue-specific biomarkers of toxic effects. Material and methods: A myocardial lipidomics based on ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC/Q-TOF MS) was developed to compare three cardiac lipid extraction methods and investigate the changes of lipids in mice heart of three different dosage groups. In addition, we concurrently inspected the biochemical parameters in plasma, observed the histology of the heart and recorded the electrocardiogram (ECG). Results: The cardiotoxicity of Fuzi was dose-dependent, and the high-dose group obviously manifested the heart damage in histology and a certain degree of arrhythmia. Significant changes of 14 lipid metabolites which primarily involved in phospholipid metabolism, sphingolipid metabolism, saturated fatty acid oxidation and unsaturated fatty acid peroxidation were identified and considered as the potential biomarkers of Fuzi toxicity. Conclusion: The lipidomics approach is helpful to search potential tissue-specific biomarkers and understand the underlying mechanisms of Fuzi toxicity on the heart. [Copyright &y& Elsevier]