Identification Markers Responsible for Differentially Processed Polygonatum cyrtonema Hua by Ultra-Performance Liquid Chromatography with Quadruple-Time-of-Flight Mass Spectrometry.

The rhizome of Polygonatum cyrtonema Hua has been used as a traditional Chinese medicine for over 2000 years. The fresh Chinese herb possesses micro toxicity and is thus traditionally alternately steamed and basked nine times to alleviate the toxicity and enhance the pharmaceutical efficacy. Different processing cycles usually result in variable therapeutic effects in the processed Polygonatum cyrtonema Hua (P-PCH). However, it can be hard to tell these various P-PCHs apart at present. To identify the P-PCHs that had undergone repeated steaming one to nine times, the chemical constituents were profiled based on Ultra-Performance Liquid Chromatography with Quadruple-Time-of-Flight Mass Spectrometry, and the Principal Component Analysis and Cluster Analysis methods were adopted to discriminate different cycles of P-PCH. A total of 44 characteristic markers were identified, which allowed the P-PCHs to be discriminated exactly.

Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species.

The aerial parts of Mosla chinensis Maxim. and Mosla chinensis cv. 'Jiangxiangru' (MCJ) are widely utilized in traditional Chinese medicine (TCM), known collectively as Xiang-ru. However, due to clinical effectiveness concerns and frequent misidentification, the original plants have increasingly been substituted by various species within the genera Elsholtzia and Mosla. The challenge in distinguishing between these genera arises from their similar morphological and metabolic profiles. To address this issue, our study introduced a rapid method for metabolic characterization, employing high-resolution mass spectrometry-based metabolomics. Through detailed biosynthetic and chemometric analyses, we pinpointed five phenolic compounds-salviaflaside, cynaroside, scutellarein-7-O-D-glucoside, rutin, and vicenin-2-among 203 identified compounds, as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia species. This methodology holds promise for broad application in the analysis of plant aerial parts, especially in verifying the authenticity of aromatic traditional medicinal plants. Our findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.

Python workflow for the selection and identification of marker peptides-proof-of-principle study with heated milk.

The analysis of almost holistic food profiles has developed considerably over the last years. This has also led to larger amounts of data and the ability to obtain more information about health-beneficial and adverse constituents in food than ever before. Especially in the field of proteomics, software is used for evaluation, and these do not provide specific approaches for unique monitoring questions. An additional and more comprehensive way of evaluation can be done with the programming language Python. It offers broad possibilities by a large ecosystem for mass spectrometric data analysis, but needs to be tailored for specific sets of features, the research questions behind. It also offers the applicability of various machine-learning approaches. The aim of the present study was to develop an algorithm for selecting and identifying potential marker peptides from mass spectrometric data. The workflow is divided into three steps: (I) feature engineering, (II) chemometric data analysis, and (III) feature identification. The first step is the transformation of the mass spectrometric data into a structure, which enables the application of existing data analysis packages in Python. The second step is the data analysis for selecting single features. These features are further processed in the third step, which is the feature identification. The data used exemplarily in this proof-of-principle approach was from a study on the influence of a heat treatment on the milk proteome/peptidome.

Screening for Forensically Relevant Drugs Using Data-Independent High-Resolution Mass Spectrometry.

Forensic and clinical laboratories are expected to provide a rapid screening of samples for a wide range of analytes; however, the ever-changing landscape of illicit substances makes analysis complicated. There is a great need for untargeted methods that can aid these laboratories in broad-scope drug screening. Liquid chromatography hyphenated with high-resolution mass spectrometry (LC-HRMS) has become a popular technique for untargeted screening and presumptive identification of drugs of abuse due to its superior sensitivity and detection capabilities in complex matrices. An untargeted extraction and data acquisition method was evaluated for the broad screening of high-priority drugs of abuse in whole blood. A total of 35 forensically relevant target analytes were identified and extracted at biologically relevant low and high (10× low) concentrations from whole blood using supported liquid extraction. Data-independent acquisition was accomplished using ultraperformance liquid chromatography and a quadrupole time-of-flight mass spectrometry. Results were acceptable for screening assays, with limits of detection at or below the recommended low-concentration cutoffs for most analytes. Analyte ionization varied from 30.1 to 267.6% (average: 110.5%) at low concentrations and from 8.6 to 383.5% (average: 93.6%) at high concentrations. Extraction recovery ranged from 8.5 to 330.5% (average: 105.3%) at low concentrations and from 9.4 to 127.5% (average: 82.7%) at high concentrations. This variability was also captured as precision, ranging from 4.7 to 135.2% (average: 36.5%) at low concentrations and from 0.9 to 59.0% (average: 21.7%) at high concentrations. The method described in this work is efficient and effective for qualitative forensic toxicology screening, as demonstrated by analysis of 166 authentic suspected impaired driver and postmortem specimens. That said, it is critical that laboratories establishing untargeted LC-HRMS screening assays be aware of the strengths and limitations across diverse drug categories and chemical structures.

Integrated metabolomics and network pharmacology study on the mechanism of herbal pair of danggui-kushen for treating ischemia heart disease.

DangGui-KuShen (DK) is a well-known classic traditional Chinese medicine recipe that improves blood circulation, eliminates moisture, and detoxifies, and is frequently used in the treatment of cardiovascular problems. Some protective effects of DK on cardiovascular disease have previously been identified, but its precise mechanism remains unknown. The goal of this study is to combine metabolomics and network pharmacology to investigate DK's protective mechanism in Ischemic Heart Disease(IHD) rat models. A combination of metabolomics and network pharmacology based on UPLC-Q-TOF/MS technology was used in this study to verify the effect of DK on IHD through enzyme-linked immunosorbent assay, HE staining, and electrocardiogram, and it was determined that DK improves the synergistic mechanism of IHD. In total, 22 serum differential metabolites and 26 urine differential metabolites were discovered, with the majority of them involved in phenylalanine, tyrosine, and tryptophan biosynthesis, glycine, serine, and threonine metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, purine metabolism, and other metabolic pathways. Furthermore, using network pharmacology, a composite target pathway network of DangGui and KuShen for treating IHD was created, which is primarily associated to the tumor necrosis factor (TNF) signaling pathway, P53 signaling, and HIF-1 signaling pathways. The combined research indicated that the NF-B signaling pathway and the HIF-1 signaling pathway are critical in DK treatment of IHD. This study clearly confirms and expands on current knowledge of the synergistic effects of DG and KS in IHD.

LC-MS based metabonomics study on protective mechanism of ESWW in cerebral ischemia via CYTC/Apaf-1/NDRG4 pathway.

BACKGROUND: Ershiwuwei Zhenzhu pills was originally recorded in the Tibetan medical book Si Bu Yi Dian in the 8th century AD and is now included in the Pharmacopoeia of the People's Republic of China (2020). The pills can calm the nerves and open the mind as well as treat cerebral ischemia reperfusion injury, stroke, hemiplegia. However, its quality standards have not yet been established, and the therapeutic effect on cerebral ischemia by regulating the mitochondrial apoptosis pathway has not been elucidated. STUDY DESIGN AND METHODS: LC-MS was used to establish quality standards for Ershiwuwei Zhenzhu pills. Metabonomics, molecular docking, neuroethology, cerebral infarction ratio, pathological detection of diencephalon, cortex, and hippocampus, and molecular biology techniques were used to reveal the mechanism of the pills in regulating the mitochondrial apoptosis pathway to treat cerebral ischemia. RESULTS: The contents of 20 chemical components in Ershiwuwei Zhenzhu pills from 12 batches and 8 manufacturers was determined for the first time. Eleven differential metabolites and three metabolic pathways, namely, fructose and mannose metabolism, glycerophospholipid metabolism, and purine metabolism, were identified by metabonomics. The pills improved the neuroethology abnormalities of MCAO rats and the pathological damage in the diencephalon and decreased the ratio of cerebral infarction. It also significantly reduced the mRNA expression of AIF, Apaf-1, cleared caspase8, CytC, and P53 mRNA in the brain tissue and the protein expression of Apaf-1 and CYTC and increased the protein expression of NDRG4. CONCLUSION: In vitro quantitative analysis of the in vitro chemical components of Ershiwuwei Zhenzhu pills has laid the foundation for improving its quality control. The potential mechanism of the pills in treating cerebral ischemia may be related to the Apaf-1/CYTC/NDRG4 apoptosis pathway. This work provides guidance for clinical drug use for patients.

[Two new benzoyl-sesquiterpenes from Mesona chinensis].

Mesona chinensis is a common medicinal and edible plant in the Lingnan region of China, which has extensive pharmacological activity. However, the study of its chemical constituents is not sufficient. In this study, a variety of modern chromatographic separation techniques were used to isolate two compounds from 95% ethanol extract of the grass parts of M. chinensis. Their absolute configurations were determined by ultraviolet spectroscopy(UV), infrared spectroscopy(IR), high resolution mass spectrometry(HR-ESI-MS), 1D and 2D nuclear magnetic resonance(1D NMR and 2D NMR), and single-crystal X-ray diffraction(SC-XRD). Specifically, they were two new benzoyl-sesquiterpenes and named mesonanol A and mesonanol B, respectively. The results of the pharmacological activity evaluation showed that neither of the two new compounds showed obvious antiviral and anti-inflammatory activities.

Preliminary investigation on the analysis of the whole components of Pogejiuxin decoction and its formulation pattern based on ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

RATIONAL: Pogejiuxin decoction (PGJXD) is one of the most important formulas for the treatment of heart failure. However, there is a great lack of research on the material basis of this formula, especially research on its compatibility laws, which restricts its clinical use. Studying the complete ingredients and compatibility rules of PGJXD has great significance for guiding clinical medication. METHODS: The entire formula, the major single herbs, the drug pairs and the disassembled formula were analyzed by ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS/MS), matching the chemical composition database and global natural product social molecular networking to explain the chemical composition as well as the combination pattern of PGJXD. RESULTS: A total of 1048 chemical constituents were fully analyzed from the major single herbs, the drug pairs and the disassembled formula and 188 chemical constituents, including 13 potential novel compounds, were firstly identified from the whole formula. We found that the chemical compositions were reduced after the single herbs were matched to the other herbs, especially the significant reduction of highly toxic diester alkaloids after compatibility, indicating that the medicines of PGJXD were interdependent and controlled by each other. CONCLUSION: This study innovatively researches and compares the compositional differences between the entire formula of PGJXD, the single, paired and separated formulas, greatly extending our understanding of the chemical substance basis of these compounds, and preliminarily explores the compatibility laws of PGJXD, providing some theoretical guidance for clinical medication.

Direct elemental analysis of plant oils by inductively coupled plasma mass spectrometry: Simple sample dilution combined with oxygen introduction into the plasma.

Assessment of trace metal concentrations in plant oils has been considered a crucial quality control marker for potential health risks, oil flavour, and oxidative stability. A straightforward inductively coupled plasma mass spectrometry (ICP-MS) methodology was developed and validated through introduction of argon:oxygen gas mixture into plasma, allowing for a direct elemental analysis of organic matrices. This approach offers the advantage of a simple one-step preparation of plant oil samples with negligible contamination risks. The complete solubilization of the oil matrix enables the determination of total metal content from a single test tube with low dilution factor of 5. The modified plasma conditions resulted in the development of a robust and accurate ICP-MS method providing limits of detection at sub ng·g-1 levels. The ICP-MS method allowed the determination of trace levels of Ba, Cd, Cu, Fe, Mn, Pb, Sn, V, and Zn in olive, sunflower and rapeseed oils.

Comparative analysis and evaluation of wild and cultivated Radix Fici Simplicissimae using an UHPLC-Q-Orbitrap mass spectrometry-based metabolomics approach.

Radix Fici Simplicissimae (RFS) is widely studied, and is in demand for its value in medicines and food products, with increased scientific focus on its cultivation and breeding. We used ultra-high-performance liquid chromatography quadrupole-orbitrap mass spectrometry-based metabolomics to elucidate the similarities and differences in phytochemical compositions of wild Radix Fici Simplicissimae (WRFS) and cultivated Radix Fici Simplicissimae (CRFS). Untargeted metabolomic analysis was performed with multivariate statistical analysis and heat maps to identify the differences. Eighty one compounds were identified from WRFS and CRFS samples. Principal component analysis and orthogonal partial least squares discrimination analysis indicated that mass spectrometry could effectively distinguish WRFS from CRFS. Among these, 17 potential biomarkers with high metabolic contents could distinguish between the two varieties, including seven phenylpropanoids, three flavonoids, one flavonol, one alkaloid, one glycoside, and four organic acids. Notably, psoralen, apigenin, and bergapten, essential metabolites that play a substantial pharmacological role in RFS, are upregulated in WRFS. WRFS and CRFS are rich in phytochemicals and are similar in terms of the compounds they contain. These findings highlight the effects of different growth environments and drug varieties on secondary metabolite compositions and provide support for targeted breeding for improved CRFS varieties.

Comprehensive Characterization of Triterpene Saponins in Rhizoma Panacis Japonici by Offline Two-Dimensional Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry.

Rhizoma Panacis Japonici (RPJ) is an ancient herbal medicine from China that has long been employed for its medicinal benefits in relieving arthritis physical debility and diverse afflictions. The primary bioactive constituents found in RPJ are triterpene saponins, which exhibit numerous pharmacological actions, including anti-inflammatory, antioxidant, and immunomodulating effects. The present study established a straightforward and effective approach for characterizing triterpene saponins in RPJ. An offline HILIC × RP LC/QTOF-MS method was developed, along with a self-constructed in-house database containing 612 saponins reported in the Panax genus and 228 predicted metabolites. The approach achieved good chromatographic performance in isolating triterpene saponins of RPJ, with the HILIC column as the first dimension (1D) and the BEH C18 column as the second dimension (2D). The developed two-dimensional liquid chromatography system exhibited an orthogonality of 0.61 and a peak capacity of 1249. Detection was performed using a QTOF mass spectrometer in a data-independent manner (MSE) in a negative ion mode. Using the in-house database, the collected MS data were processed by an automatic workflow on UNIFI 1.8.2 software, which included data correction, matching of precursor and product ions, and peak annotation. In this study, 307 saponins were characterized from RPJ and 76 saponins were identified for the first time in Panax japonicus. This research not only enhances our understanding of the chemical characteristics of RPJ but also offers a simple and efficient method for analyzing the complex composition of herbal medicine.

Multiple-matrices metabolomics combined with serum pharmacochemistry for discovering the potential targets and active constituents of Qifu decoction against heart failure.

Qifu decoction (QFD) is an ancient traditional Chinese medicine (TCM) prescription for the treatment of heart failure. However, the mechanisms and active constituents of QFD are poorly understood. In this study, multi-matrices metabolomics (serum, urine, and myocardial mitochondria) based on ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOFMS), were employed for exploring the mechanisms of QFD against heart failure in rat model. Twenty-one, seventeen, and fifteen endogenous metabolite biomarkers associated with heart failure were identified from serum, urine, and myocardial mitochondria datasets, respectively. Fourteen, twelve, and ten of the identified serum, urine, and mitochondria biomarkers were significantly reversed by QFD, respectively. QFD-targeted pathways were involved in TCA cycle, branched chain amino acids metabolism, fatty acid ß-oxidation, sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, tryptophan metabolism, purine metabolism. In addition, QFD-derived constituents in serum were fully analyzed by UHPLC-Q-TOFMS and SUS-plot, and 24 QFD-derived components were identified in serum. Then, the correlation analysis between the QFD-reversed serum biomarkers and QFD-derived constituents in serum was employed to dissect the active constituents of QFD. It was found that eight prototypical components and three metabolites were highly correlated with efficacy and could serve as the active constituents of QFD against heart failure. Finally, neoline and calycosin, which highly correlated with branched-chain amino acid metabolism and fatty acid ß-oxidation, were selected to validate in Na2S2O4-induced cell model. It was found that neoline and calycosin provided a significant protective effect against Na2S2O4-induced cell death in a low dose-dependent manner and increased the expressions of the pathway-related protein CPT1B and BCAT2 in the cell model. In conclusions, these findings provided light on the mechanisms and active constituents of QFD against heart failure. Neoline and calycosin could be selected as potential quality-markers of QFD against heart failure.

Resultant compound from sublimation test for Gentianae Radix in Japanese Pharmacopoeia was 5-(hydroxymethyl)furfural.

Gentianae Radix, an herbal medicine, has been used as a gastrointestinal drug in Japan. In the Japanese Pharmacopoeia 18th Revision, the sublimation test is specified as an identification test for Gentianae Radix. The compound obtained in this sublimation test was believed to be gentisin, a xanthone family compound. However, the compound we identified using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and 1H- and 13C-NMR was 5-(hydroxymethyl)furfural (5-HMF). The same compound was found to be a sublimate of Gentianae Scabrae Radix and Gentianae Macrophyllae Radix, belonging to the same genus as Gentianae Radix. These results indicate the necessity to revise the identification test for Gentianae Radix to a more unique method.

Native Mass Spectrometry Dissects the Structural Dynamics of an Allosteric Heterodimer of SARS-CoV-2 Nonstructural Proteins.

Structure-based drug design, which relies on precise understanding of the target protein and its interaction with the drug candidate, is dramatically expedited by advances in computational methods for candidate prediction. Yet, the accuracy needs to be improved with more structural data from high throughput experiments, which are challenging to generate, especially for dynamic and weak associations. Herein, we applied native mass spectrometry (native MS) to rapidly characterize ligand binding of an allosteric heterodimeric complex of SARS-CoV-2 nonstructural proteins (nsp) nsp10 and nsp16 (nsp10/16), a complex essential for virus survival in the host and thus a desirable drug target. Native MS showed that the dimer is in equilibrium with monomeric states in solution. Consistent with the literature, well characterized small cosubstrate, RNA substrate, and product bind with high specificity and affinity to the dimer but not the free monomers. Unsuccessfully designed ligands bind indiscriminately to all forms. Using neutral gas collision, the nsp16 monomer with bound cosubstrate can be released from the holo dimer complex, confirming the binding to nsp16 as revealed by the crystal structure. However, we observed an unusual migration of the endogenous zinc ions bound to nsp10 to nsp16 after collisional dissociation. The metal migration can be suppressed by using surface collision with reduced precursor charge states, which presumably resulted in minimal gas-phase structural rearrangement and highlighted the importance of complementary techniques. With minimal sample input (∼µg), native MS can rapidly detect ligand binding affinities and locations in dynamic multisubunit protein complexes, demonstrating the potential of an "all-in-one" native MS assay for rapid structural profiling of protein-to-AI-based compound systems to expedite drug discovery.

A novel strategy for the quality control of carbonized Typhae pollen using colorimeter, liquid chromatography-mass spectrometry, and efficacy evaluation coupled with multivariate statistical analysis.

In this study, a novel quality control strategy was proposed, aiming to establish a multivariate specification for the processing step by exploring the correlation between colors, chemical components, and hemostatic effects of the carbonized Typhae pollen (CTP) using multivariate statistical analysis. The CTP samples were stir-fried at different durations. Afterward, the colorimeter and LC-MS techniques were applied to characterize the CTP samples, followed by the determination of bleeding time and clotting time using mice to evaluate their hemostatic effect. Then, principal component analysis, hierarchical cluster analysis, and multi-block partial least squares were used for data analysis on colors, chemical components, and their correlation with the hemostatic effect. Consequently, 13 critical quality attributes (CQAs) of CTP were identified via multivariate statistical analysis-L*, a*, b*, 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, 3-hydroxybenzoic acid, quercetin-3-O-glucoside, azelaic acid, kaempferol-3-O-glucoside, quercetin, naringenin, kaempferol, and isorhamnetin. The multivariate specification method involving the 13 CQAs was developed and visualized in the latent variable space of the partial least squares model, indicating that the proposed method was successfully applied to assess the quality of CTP and the degree of carbonization. Most importantly, this study offers a novel insight into the control of processing for carbonized Chinese herbal medicines.

Chemical characterization, multivariate analysis and comparison of biological activities of different parts of Fraxinus mandshurica.

Fraxinus mandshurica (Oleaceae) is used as a traditional medicinal plant for the treatment of red eyes, menstrual disorders, excessive leucorrhea, chronic bronchitis and psoriasis. To perform chemical characterization of the secondary metabolites of F. mandshurica roots, bark, stems and leaves, 32 samples were collected from eight provinces in this study. A total of 64 chemical components were detected from four different parts of F. mandshurica by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Meanwhile, a total of nine secoiridoids were obtained by natural product chemical extraction, isolation and identification methods. Quantitative analysis by high-performance liquid chromatography-diode array detection-mass spectrometry showed the highest total content of secoiridoids in the bark, which is also consistent with the traditional medicinal parts. The results of methodological validation showed that the correlation coefficient (R2) values were all >0.9993, indicating a good linear range of the standard curve, while the relative standard deviations of precision, reproducibility and stability were <3%, and the spiked recoveries ranged from 98.22 to 102.27%, indicating that the experimental method was reliable and stable. In addition, fingerprinting and a heatmap were established to demonstrate the content trends of F. mandshurica more visually from different origins. Multivariate analysis, including principal component analysis and partial least squares discriminant analysis, was performed to determine the chemical characteristics of different parts of F. mandshurica, and six characteristic secoiridoids that could be used to distinguish different origins were screened. Finally, the inhibition of tyrosinase, α-glucosidase, acetylcholinesterase and pancreatic lipase activities by the nine characteristic compounds and extracts from different parts were investigated, and the results showed that they all exhibited different degrees of enzyme activity inhibition and thus have potential applications in whitening and blemish removal, hypoglycemia, anti-Alzheimer's disease and anti-obesity as a new source of natural enzyme activity inhibitors. This study establishes an identification and evaluation method applicable to phytochemistry of different origins, which is a guideline for quality control, origin evaluation and clinical application of traditional medicinal plants. This is also an unprecedented study on the identification of the chemical composition of different parts of F. mandshurica, characteristic compounds and the inhibition of enzyme activity of extracts from different parts.

Lipidomic changes in a novel sepsis outcome-based analysis reveals potent pro-inflammatory and pro-resolving signaling lipids.

The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of sepsis recognition. Patients meeting Sepsis-3 criteria were enrolled from the emergency department or intensive care unit and blood samples were obtained. Clinical data were collected and outcomes of rapid recovery, chronic critical illness (CCI), or early death were adjudicated by clinicians. Lipidomic analysis was performed on two platforms, the Sciex™ 5500 device to perform a lipidomic screen of 1450 lipid species and a targeted signaling lipid panel using liquid-chromatography tandem mass spectrometry. For the lipidomic screen, there were 274 patients with sepsis: 192 with rapid recovery, 47 with CCI, and 35 with early deaths. CCI and early death patients were grouped together for analysis. Fatty acid (FA) 12:0 was decreased in CCI/early death, whereas FA 17:0 and 20:1 were elevated in CCI/early death, compared to rapid recovery patients. For the signaling lipid panel analysis, there were 262 patients with sepsis: 189 with rapid recovery, 45 with CCI, and 28 with early death. Pro-inflammatory signaling lipids from ω-6 poly-unsaturated fatty acids (PUFAs), including 15-hydroxyeicosatetraenoic (HETE), 12-HETE, and 11-HETE (oxidation products of arachidonic acid [AA]) were elevated in CCI/early death patients compared to rapid recovery. The pro-resolving lipid mediator from ω-3 PUFAs, 14(S)-hydroxy docosahexaenoic acid (14S-HDHA), was also elevated in CCI/early death compared to rapid recovery. Signaling lipids of the AA pathway were elevated in poor-outcome patients with sepsis and may serve as targets for future therapies.

A quantitative chemomics strategy for the comprehensive comparison of Murraya paniculata and M. exotica using liquid chromatography coupled with mass spectrometry.

Murrayae Folium et Cacumen (MFC) is a traditional Chinese medicine (TCM) derived from two plant species, Murraya exotica L. and Murraya paniculata (L.) Jack, as recorded in the Chinese Pharmacopoeia. However, there is no research available on the comprehensive analysis and comparison of the chemical constituents of these two species. In the present study, an integrated LC-MS-based quantitative metabolome strategy was proposed to conduct a comprehensive and in-depth qualitative and quantitative analysis and comparison of the chemome of M. exotica and M. paniculata. Firstly, the universal chemical information of two plants was obtained by quadrupole-time-of-flight mass spectrometry (Q-TOF-MS) combined with hybrid triple quadrupole-linear ion trap mass spectrometry (Qtrap-MS). Subsequently, a UNIFI in house database, the proposed fragmentation patterns, and a quantitative structure chromatographic retention relationship (QSRR) model were integrated for the rapid, comprehensive, and accurate structural elucidation of the chemical constituents of these two species. Thirdly, a large-scale quantitation method was established using scheduled multiple reaction monitoring mode (sMRM) and 76 primary components were selected as quantitative markers for the method validation. The obtained dataset was then subjected for multivariate statistical analysis to comprehensive comparison of these two plants. As a result, a total of 209 and 212 compounds were identified from M. exotica and M. paniculata, respectively. Among them, 103 common constituents were disclosed in both plants. The multivariate statistical analysis and absolute quantitative analysis revealed noticeable differences in the contents of specific chemical constituents between these two plants. The higher quantity constituents in M. exotica are 7-methoxycoumarins, while polymethoxylated flavonoids are the major constituents in M. paniculata. The common compounds accounted for approximately 80 % of the quantitative components in both plants, which provides a theoretical basis for their common use as the official source of MFC. In sum, the established quantitative chemomics strategy supplies an effective means for comprehensive chemical comparison of multi-source TCMs.

Correlation between Selenium and Zinc Levels and Survival among Prostate Cancer Patients.

The most prevalent type of cancer among males is prostate cancer. Survival is considered quite good, but it can be further improved when risk factors are optimized. One of these factors is micronutrients, including Se and Zn. To our knowledge, the interaction between Se and Zn and prostate cancer remains undescribed. This study aimed to investigate the optimal levels of selenium (Se) and zinc (Zn) and their impact on the survival of individuals diagnosed with prostate cancer. A total of 338 prostate cancer patients were enrolled in this study, which was conducted in Poland between 2009 and 2015. Mass spectrometry, which uses inductively coupled plasma mass, was used to assess serum element levels before treatment. The study participants were categorized into quartiles (QI-QIV) based on the distributions of Se and Zn levels observed among surviving participants. Cox regression was used to assess the association between serum Se and Zn levels and the survival of prostate cancer patients. Our results reveal the effect of combined Se and Zn levels on survival in prostate cancer patients (SeQI-ZnQI vs. SeQIV-ZnQIV; HR = 20.9). These results need further research to establish Se/Zn norms for different populations.

Spatial metabolome of biosynthesis and metabolism in Cyclocarya paliurus leaves.

A large number of plant metabolites were discovered, but their biosynthetic and metabolic pathways are still largely unknown. However, the spatial distribution of metabolites and their changes in metabolic pathways can be supplemented by mass spectrometry imaging (MSI) techniques. For this purpose, the combination of desorption electrospray ionization (DESI)-MSI and non-targeted metabolomics was used to obtain the spatial distribution information of metabolites in the leaves of Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus). The sample pretreatment method was optimized to have higher detection sensitivity in DESI. The changes of metabolites in C. paliurus were analyzed in depth with the integration of the spatial distribution information of metabolites. The main pathways for biosynthesis of flavonoid precursor and the effect of changes in compound structure on the spatial distribution were found. Spatial metabolomics can provide more metabolite information and a platform for the in-depth understanding of the biosynthesis and metabolism in plants.