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Existing approaches for predicting total water storage (TWS) rely on land surface or hydrological models using meteorological forcing data. Yet, such models are more adept at predicting specific water compartments, such as soil moisture, rather than others, which consequently impedes accurately forecasting of TWS. Here we show that machine learning can be used to uncover relations between nonseasonal terms of Gravity Recovery and Climate Experiment (GRACE) derived total water storage and the preceding hydrometeorological drivers, and these relations can subsequently be used to predict water storage up to 12 months ahead, and even exceptional droughts on the basis of near real‐time observational forcing data. Validation by actual GRACE observations suggests that the method developed here has the capability to forecast trends in global land water storage for the following year. If applied in early warning systems, these predictions would better inform decision‐makers to improve current drought and water resource management. Plain Language Summary: Traditional methods for predicting short‐term/seasonal variations in land total water storages rely on hydrological models. However, these models have a drawback—they are better at predicting water stored in specific parts of the land system like soil moisture than giving an accurate forecast for the overall integrated land total water storage. In this study, we demonstrate the applicability of machine learning in uncovering relationships between the de‐season and de‐linearized terms of global water storage variability as observed by the Gravity Recovery and Climate Experiment (GRACE) satellites, and the preceding hydrometeorological variables such as sea surface temperature. These relationships can then be utilized to forecast monthly changes in land total water storage up to 1 year ahead, and even to predict exceptional drought events based on near real‐time observational forcing data. The validation by actual GRACE observations, lends further credence to the effectiveness of the method developed here, showcasing its potential to forecast trends in global land total water storage for the upcoming year. The potential applications of these predictions in early warning systems are highly promising, and we anticipate that they can assist decision‐makers in enhancing current drought and water resource management practices. Key Points: We identify a stable lag relationship between hydrometeorological variables and the GRACE derived total water storage change (TWSC)Using this stable lag relationship, we are able to forecast the global TWSC up to 1 year ahead with solely observational data as inputsOur forecasts exhibit high consistency with actual GRACE data in terms of global mean land water storage trends for the following year [ABSTRACT FROM AUTHOR]

Background: Natural medicines present a considerable analytical challenge due to their diverse botanical origins and complex multi‐species composition. This inherent complexity complicates their rapid identification and analysis. Tangerine peel, a product of the Citrus species from the Rutaceae family, is widely used both as a culinary ingredient and in traditional Chinese medicine. It is classified into two primary types in China: Citri Reticulatae Pericarpium (CP) and Citri Reticulatae Pericarpium Viride (QP), differentiated by harvest time. A notable price disparity exists between CP and another variety, Citri reticulatae "Chachi" (GCP), with differences being based on the original variety. Methods: This study introduces an innovative method using portable miniature mass spectrometry for swift on‐site analysis of QP, CP, and GCP, requiring less than a minute per sample. And combined with machine learning to differentiate the three types on site, the method was used to try to distinguish GCP from different storage years. Results: This novel method using portable miniature mass spectrometry for swift on‐site analysis of tangerine peels enabled the characterization of 22 compounds in less than one minute per sample. The method simplifies sample processing and integrates machine learning to distinguish between the CP, QP, and GCP varieties. Moreover, a multiple‐perceptron neural network model is further employed to specifically differentiate between CP and GCP, addressing the significant price gap between them. Conclusions: The entire analytical time of the method is about 1 minute, and samples can be analyzed on site, greatly reducing the cost of testing. Besides, this approach is versatile, operates independently of location and environmental conditions, and offers a valuable tool for assessing the quality of natural medicines. [ABSTRACT FROM AUTHOR]

Groundwater potential maps are crucial tools for effectively managing water resources, particularly in agriculturally focused countries such as Vietnam. However, creating these maps is a challenging task that requires reliable data and methods. In this study, we integrated the Split‐Point Sampling and Node Attribute Subsampling Classifier (SPAARC) with the Bagging (B), MultiBoostAB (MBAB), and Random Subspace (RSS) ensemble learning techniques and developed three ensemble models: B‐SPAARC, MBAB‐SPAARC, and RSS‐SPAARC. We selected 13 geoenvironmental factors based on their availability, relevance, and association with groundwater potential in the Sesan River basin of Vietnam. We assessed the models' performance using various metrics such as area under the curve (AUC), accuracy, sensitivity, specificity, and RMSE. The findings indicated that the ensemble models performed better than the single SPAARC model in mapping groundwater potential. The MBAB‐SPAARC model demonstrated the highest accuracy with an AUC value of 0.891, followed by B‐SPAARC (AUC = 0.844), RSS‐SPAARC (AUC = 0.871), and the single SPAARC (AUC = 0.853) models. The results also highlighted that elevation, rainfall, land use/cover, and altitude were the most significant factors for mapping groundwater potential in the Sesan River basin. The innovative ensemble models and reliable potential maps developed in this study assist water resource managers in planning water usage based on the benefits and costs for various users and in devising sustainable strategies for using, protecting, and managing groundwater. Key Points: Groundwater potential mapping was carried out at the Central Highlands of VietnamHybrid Machine learning Models based on Naïve Bayes Tree were developed and usedResults showed that the proposal models are potential and accurate tools [ABSTRACT FROM AUTHOR]

This study systematically analyzed the molecular mechanism and function of nuclear factor kappa B subunit 2 (NFKB2) in colorectal cancer (CRC) to investigate the potential of NFKB2 as a therapeutic target for CRC. Various experimental techniques, including RNA sequencing, proteome chip assays, and small molecule analysis, were used to obtain a deeper understanding of the regulation of NFKB2 in CRC. The results revealed that NFKB2 was upregulated in a significant proportion of patients with advanced hepatic metastasis of CRC. NFKB2 played an important role in promoting tumor growth through CD8+ T‐cell exhaustion. Moreover, NFKB2 directly interacted with signal transducer and activator of transcription 2 (STAT2), leading to increased phosphorylation of STAT2 and the upregulation of programmed death ligand 1 (PD‐L1). Applying a small molecule inhibitor of NFKB2 (Rg5) led to a reduction in PD‐L1 expression and improved response to programmed death‐1 blockade‐based immunotherapy. In conclusion, the facilitated NFKB2‐STAT2/PD‐L1 axis may suppress immune surveillance in CRC and targeting NFKB2 may enhance the efficacy of immunotherapeutic strategies. Our results provide novel insights into the molecular mechanisms underlying the contribution of NFKB2 in CRC immune escape. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic value of musculoskeletal ultrasound measurements of subacromial bursa (SAB) thickness, supraspinatus tendon (SUP) thickness, acromiohumeral distance (AHD), and SUP‐to‐AHD ratio (AHD%) in patients with shoulder impingement syndrome (SIS). Methods: This was a prospective cross‐sectional observational study. Thirty patients with SIS (60 shoulders) admitted between January 2019 and January 2020 were enrolled. The SUP thickness, SAB thickness, AHD, and AHD% (calculated as AHD% = [(SUP / AHD) × 100%]) were measured in 60 shoulders using musculoskeletal ultrasound. Results: The affected shoulder displayed thicker SUP and SAB (t = 7.838), narrower AHD (t = 2.324), and larger AHD% (t = 6.875) than the unaffected shoulder (P <.05). The SUP thickness showed a linear positive correlation with AHD (r =.503) and AHD% (r =.792) in the affected shoulder (P <.05). On receiver operating characteristic analysis, AHD*AHD% showed the best diagnostic performance in both measurements (area under the curve: 0.877). Conclusion: This study revealed that SIS symptoms may be related to a larger AHD% with SUP thickening. As diagnostic criteria, the cut‐off values of AHD% (65.6%) and AHD*AHD% (0.504) have good sensitivity and specificity and can help improve the differential diagnosis of patients with SIS. [ABSTRACT FROM AUTHOR]

Background: The renin–angiotensin system produces a series of biologically active angiotensin (Ang) peptides. These Ang peptides are the major regulators of blood pressure and Na homeostasis, and play a critical role in maintaining cardiovascular and fluid homeostasis. The concentration of Ang peptides in the body is at trace levels, making their detection and quantification a challenge. In this study, a rapid and sensitive analytical method using mass spectrometry coupled with ultrahigh‐performance liquid chromatography (UHPLC/MS) was developed to simultaneously quantify 14 Ang peptides. Methods: UHPLC/MS was employed to quantify 14 Ang peptides in mouse and human plasma. An HSS T3 column (2.1 × 100 mm, 1.8 μm) with an HSS T3 precolumn and triple‐quadrupole mass spectrometer combined with an electrospray ionization source were utilized. Sample pretreatment involved a one‐step protein precipitation using methanol. The total analysis time was within 7.5 min and the target peptides were detected in positive ion mode and quantified by selected reaction monitoring mode. Results: The method was validated for linearity, detection and quantification limits, precision, stability, recovery and matrix effect. The limits of detection of Ang II, Ang III, Ang‐(1–7), Ang‐(2–7), Ang‐(3–7), Ang‐(1–9), bradykinin, Asn1 and Val5‐Ang II are all less than 1 pg mL−1, indicating high sensitivity. The intra‐day and inter‐day precision was within 15%, and the accuracy was between 85% and 115%. Meanwhile, the sample and reference solution were stable within 48 h, and the recovery and matrix effect met the quantitative requirements. Conclusions: The method is currently reported to allow the largest number of Ang peptide species to be detected at one time. In addition, the proposed method offers a fast and reliable approach for comprehensive analysis of Ang metabolism in biological samples, facilitating research on the physiological and pathological states of cardiovascular, kidney and respiratory diseases. [ABSTRACT FROM AUTHOR]

Safety issues caused by pharmaceuticals have frequently occurred worldwide, posing a tremendous threat to human health. As an essential part of drug development, the toxicological analysis and safety evaluation is of great significance. In addition, the risk of pharmaceuticals accumulation in the environment and the monitoring of the toxicity from natural medicines have also received ongoing concerns. Due to a lack of spatial distribution information provided by common analytical methods, analyses that provide spatial dimensions could serve as complementary safety evaluation methods for better prediction and evaluation of drug toxicity. With advances in technical solutions and software algorithms, mass spectrometry imaging (MSI) has received increasing attention as a popular analytical tool that enables the simultaneous implementation of qualitative, quantitative, and localization without complex sample pretreatment and labeling steps. In recent years, MSI has become more attractive, powerful, and sensitive and has been applied in several scientific fields that can meet the safety assessment requirements. This review aims to cover a detailed summary of the various MSI technologies utilized in the biomedical and pharmaceutical area, including technical principles, advantages, current status, and future trends. Representative applications and developments in the safety‐related issues of different pharmaceuticals and natural medicines are also described to provide a reference for pharmaceutical research, improve rational clinical medicine use, and ensure public safety. [ABSTRACT FROM AUTHOR]

The Amundsen Sea (AS) sector in West Antarctica accounts for a significant proportion of Earth's ice losses and is the largest contributor of Antarctica's mass loss. To evaluate its contribution to global sea‐level rise, we reconstruct the long‐term continuous surface elevation changes (CSEC) record of the AS sector by an improved least‐squares plane fitting method (ILSPFM), which merged the relative surface elevation change (SEC) series instead of height from Envisat, ICESat, CryoSat‐2, and ICESat‐2 missions during 2003–2021. The accuracy of CSEC is improved by 25.9% using ILSPFM. The average rate of CSEC in the AS sector was −24.25 ± 0.48 cm yr−1 during 2003–2021. The largest signals of SEC are found over Pine Island, Thwaites, and Pope Glaciers, with the largest decline of SEC over Pope Glacier with a total SEC of −82.44 ± 7.21 m and an annual change rate of −4.34 ± 0.38 m yr−1. The ridge between Pine Island and Thwaites Glaciers is found in the AS sector, indicating that the change of ice sheet is dynamic thinning and closely related to the topography and the distance from the grounding line. Compared with meteorological data sets, we find that the codirectional fluctuation in CSEC is delayed by 3 months with surface temperature, and the precipitation leading SEC series as the phase arrow points straight down from the cross wavelet transform. Our new record shows that the AS sector thinned rapidly from 2003 to 2021 but decelerated from 2019 to 2021, and it was clearly correlated to the surface temperature, precipitation, and local terrain. Plain Language Summary: With the intensification of global climate change, the melting of glaciers and ice shelves around the Amundsen Sea (AS) sector in Antarctica has caused a large amount of glacial meltwater to flow into the ocean, directly leading to the rapid rise of global sea levels. Therefore, it is of great scientific and practical significance to determine the high‐precision, high‐resolution, and long‐term continuous ice sheet surface elevation change (SEC) to predict future global sea‐level changes. Considering the different characteristics and abilities of different altimeter missions, we developed an improved least‐squares plane fitting method (ILSPFM) to merge radar and laser multi‐mission satellite altimetry. The ILSPFM is applied to reconstruct the 2003–2021 ice sheet continuous SEC (CSEC) record in the AS sector using Envisat, ICESat, ICESat‐2, and CryoSat‐2 observations, and it is compared to IceBridge and GRACE Mascon products. The root mean square errors of CSEC is improved by 25.9% compared with the simple combination of individual SEC series from Envisat/ICESat/CryoSat‐2/ICESat‐2. This study highlights the potential of the CSEC multi‐mission series determined by the ILSPFM as a reliable data set to support our understanding of the response mechanism of glaciers to climate change and for predicting global sea‐level changes. Key Points: An improved least‐squares plane fitting method is proposed to merge radar and laser multi‐altimeter data in the Amundsen Sea (AS) sectorContinuous surface elevation change data set (2003–2021) in AS sector is reconstructed with the average rate −24.25 ± 0.48 cm/yrOur new record shows that the AS sector thinned rapidly from 2003 to 2021 but decelerated from 2019 to 2021 [ABSTRACT FROM AUTHOR]

Organohalogens play an important role in the drug discovery and functional materials. However, the convenient preparation of organohalogens still remains a challenging task. Herein, we report a metal‐free cascade dihalogenation‐cyclization of cyclohexadienone‐containing 1,6‐enynes in a biodegradable solvent to generate the dibrominated cis‐tetrahydrobenzofuran‐5(4H)‐ones and cis‐dihydrobenzopyran‐6(5H)‐ones respectively bearing 1,4‐dibromobut‐1‐enyl subunit in trans‐trans and trans‐cis form. A subgram‐scale experiment and several downstream transformations are presented for elaborating the synthetic utility. Moreover, the potent anticancer activity is observed against MDA‐MB‐468 cells for the corresponding products. [ABSTRACT FROM AUTHOR]

Owing to increasing demand for Panax notoginseng‐based medicines and health products, establishing a fast, simple, and reliable assay to analyze the chemical differences between its root and rhizome is important. Although previous studies showed that the chemical and biological differences between the root and rhizome of P. notoginseng seem to be small, efforts should be taken to investigate such differences to ensure the safety and efficacy of the products. This work describes a holistic approach that combines characteristic fingerprinting using ultra‐high performance liquid chromatography‐tandem mass spectrometry parent ion scanning with charged aerosol detection and targeted separation by online heart‐cutting two‐dimensional liquid chromatography, to identify and evaluate characteristic markers allowing differentiation of the root and rhizome. A total of five potential markers chikusetsusaponin L5, ginsenoside Rb2, stipuleanoside R2, malonyl‐ginsenoside Rb1, and malonyl‐ginsenoside Rd, were identified and confirmed by comparing chromatographic retention time, the accurate mass of molecular weight, and the fragments of secondary MS with the available reference materials. The results showed that all five markers were 2.8–7 times higher in content in the rhizome than in the root. [ABSTRACT FROM AUTHOR]

Rationale: Bear bile powder (BBP) is a widely used traditional Chinese medicine (TCM), and bile acids (BAs) are the main active components in BBP. Due to the scarcity of BBP resources, adulterations often occur in the market. Conventional methods to distinguish them are usually complicated and time‐consuming. To enhance effectiveness and accuracy, a rapid and rough analytical method is desperately needed. Methods: In this study, a rapid strategy using chip‐based nano‐electrospray ionization tandem mass spectrometry (nano‐ESI‐MS/MS) was established to distinguish BBP from other sources of bile powder (BP). In addition, the results were further verified by ultra‐high‐performance liquid chromatography combined with high‐resolution mass spectrometry (UPLC/MS). Results: The precision of the chip‐based nano‐ESI‐MS/MS method was validated to be acceptable with relative standard deviation (RSD) <15%. The distinction between BBP and other sources of BP, including common adulterants of pig bile powder (PBP), cattle bile powder (CBP), sheep bile powder (SBP), and chicken bile powder (CkBP), can be observed in the spectra. By using orthogonal partial least‐squares discriminant analysis (OPLS‐DA), more potential m/z markers were investigated. A BAs‐related m/z marker of 498.3 was discovered as a typical differential molecular ion peak and was identified as tauroursodeoxycholic acid (TUDCA) and taurochenodeoxycholic acid (TCDCA) in BBP. Conclusions: The proposed strategy has simple sample pretreatment steps and significantly shortened analysis time. As an emerging technology, chip‐based nano‐ESI‐MS not only provides a reference for the rapid distinction of adulterated Chinese medicines, but also provides some insights into the identification of other chemicals and foods. [ABSTRACT FROM AUTHOR]

As one of the major diabetic microvascular complications, diabetic retinopathy (DR) is mainly initiated by the blood‐retinal barrier (BRB) dysfunction. Chlorogenic acid (CGA) is a natural polyphenolic compound in Lonicerae Japonicae Flos, which traditionally has the beneficial function for eyes and is commonly included in many anti‐diabetic formulas. In this study, the potential protective mechanism of CGA against DR was investigated. Streptozotocin (STZ) was used to induce diabetes in mice. CGA attenuated BRB dysfunction and reversed endothelial‐mesenchymal transition (EndoMT) and epithelial‐mesenchymal transition (EMT) in retinas in vivo. CGA inhibited microglia activation and reduced tumor necrosis factor (TNF)α release both in vivo and in vitro. CGA promoted nuclear factor erythroid 2‐related factor 2 (Nrf2) activation and prevented EndoMT/EMT in TNFα‐treated human retinal endothelial cells (HRECs) or retinal pigment epithelial APRE19 cells. CGA alleviated endothelial/epithelial barrier oxidative injury in HRECs or APRE19 cells stimulated with TNFα, but this effect was disappeared in cells co‐incubated with Nrf2 inhibitor. Additionally, the CGA‐supplied alleviation on BRB damage and EndoMT/EMT was markedly weakened in retinas from STZ‐treated Nrf2 knock‐out mice. All results suggest that CGA improves DR through attenuating BRB injury by reducing microglia‐initiated inflammation and preventing TNFα‐induced EndoMT/EMT and oxidative injury via inducing Nrf2 activation. [ABSTRACT FROM AUTHOR]

The Gravity Recovery and Climate Experiment (GRACE) mission has monitored global total water storage anomalies (TWSA) with an unprecedented accuracy since 2002. Yet, many applications require a longer record, that is, extending prior to the GRACE period. Here, we present a new global reconstruction of long‐term (1979–2020) TWSA fields by combining machine learning with time series decomposition and statistical decomposition techniques. We find that the long‐term TWSA reconstructed from GRACE fits well with the GRACE‐FO observation over most grids (0.5° resolution) of the global land and successfully reproduces the strong El Niño signal. Comparisons to Satellite Laser Ranging solutions and to observed global mean sea level change suggest our reconstruction (doi: https://doi.org/10.5061/dryad.z612jm6bt) is more reliable than previously published products. This study provides a viable approach for both reconstructing past TWSA and filling the GRACE data gap at the global scale. Plain Language Summary: Since 2002, temporal changes of vertically integrated water storage have been detected globally with unprecedented accuracy via satellite gravimetry, as first implemented with the Gravity Recovery and Climate Experiment (GRACE) satellites. However, no similar observation system has been in place before 2002, that could have used to measure the total water storage anomalies (TWSA) with an accuracy comparable to GRACE. Several approaches, such as machine learning, have been proposed in previous studies to reconstruct past TWSA based on their empirical relationships with the climatic/hydrological drivers (e.g., precipitation and soil moisture). Different from traditional approaches, we here combine machine learning with statistical decomposition techniques to reconstruct GRACE‐like TWSA (0.5° resolution) for the period 1979–2020 over the global land. We find that the reconstructed TWSA shows strong abnormal signals during El Niño years. In addition, we compare our reconstruction to recent TWSA data obtained using Satellite Laser Ranging analysis to five satellites, that is, Lageos‐1, Lageos‐2, Ajisai, Stella, and Starlette, in the period since 1993, and to the observed global mean sea level change as validations. The comparison suggests that our reconstruction is more accurate than previously published products. We suggest our method provides a viable alternative for reconstructing long‐term TWSA. Key Points: We reconstruct Gravity Recovery and Climate Experiment‐like (GRACE) total water storage anomaly (TWSA) fields over the global land surface for the period 1979–2020TWSA reconstructed from GRACE fit well with GRACE Follow‐On data and correctly reproduce strong El Niño signalsOutside the GRACE period, our reconstruction fits better with satellite laser ranging solutions and global mean sea level than previous reconstruction [ABSTRACT FROM AUTHOR]

Notoginsenoside Ft1 (NGFt1), a dammarane triterpene glycoside isolated from Panax notoginseng, showed potent effective in stimulating platelet aggregation in our previous assay, yet its pharmacokinetic behavior is still unclear. This study describes a rapid and sensitive ultra‐high‐pressure LC–tandem mass spectrometry assay for determining of NGFt1 in rat plasma. Methanol‐mediated precipitation was used for sample pre‐treatment. Chromatographic separation was achieved on a C18 column with gradient elution using water and acetonitrile as mobile phase. Determination was obtained using an electrospray ionization source in negative selected reaction monitoring (SRM) mode at the transitions of m/z 915.9 → m/z 783.8 and m/z 799.8 → m/z 637.8 for NGFt1 and internal standard, respectively. The assay was linear over the concentration range 0.25–2500 ng/mL (r > 0.995) with the lower limit of quantification of 0.25 ng/mL. The intra‐ and inter‐day precisions (relative standard deviation, %) ranged 1.65%–9.84% and 2.46%–13.49%, respectively, whereas accuracy (relative recovery, %) ranged from 96.21% to 99.45%, respectively. The recovery ranged from 95.09% to 102.22% and the matrix effect from 98.29% to 100.13%. The analyte was stable under tested storage conditions. The method has been successfully applied to a preclinical pharmacokinetic study in rats after a single intravenous (2 mg/kg) and oral (50 mg/kg) administration. [ABSTRACT FROM AUTHOR]

Deep eutectic solvents have received increasing attention over the past decade, and the green and versatile nature makes them important media for developing environmentally friendly and sustainable technologies. In addition to act as green alternatives to traditional organic solvents, deep eutectic solvents offer tremendous opportunities to produce different kinds of emerging functional materials. The present review highlights the recent development and applications of deep functional materials based on deep eutectic solvents as novel adsorbents for diverse analytes in complex matrices. The type, preparation, and unique properties of deep eutectic solvents, the synthesis of deep eutectic solvent derived materials, as well as their applications in chromatographic separation are described. We aim to demonstrate that deep eutectic solvents not only allow the design of eco‐friendly extraction processes but also open straightforward access to advanced materials in sample preparation. [ABSTRACT FROM AUTHOR]

Lusianthridin, a bioactive component isolated from Dendrobium venustum, has been demonstrated to have many biological properties such as antioxidant and anticancer activities. However, the metabolic profiles remain unknown. This study was carried out to investigate the metabolic profiles of lusianthridin in liver microsomes. Lusianthridin was co‐incubated with liver microsomes in the presence of nicotinamide adenine dinucleotide phosphate and UDP‐glucuronic acid or glutathione at 37°C for 1 h. The incubation samples were analyzed by liquid chromatography combined with electrospray ionization high‐resolution mass spectrometry. The data were acquired and processed. The structures of the metabolites were proposed by comparing their accurate mass and MS2 spectra with those of the parent compound. A total of 15 metabolites were detected in vitro, including two phase I and 13 phase II metabolites. The phase I metabolic pathways were oxidation, demethylation and dehydrogenation. The phase II metabolic pathways referred to glucuronidation and glutathione conjugation. The present study provides an overview pertaining to the metabolic profiles of lusianthridin in vitro, which is indispensable for understanding the efficacy and safety of lusianthridin, as well as the herbal medicine D. venustum. [ABSTRACT FROM AUTHOR]

Introduction: Agarwood is a highly valuable fragrant resinous wood which is widely used as traditional Chinese medicines, perfumes, incense and decorations. Due to its high economic value and excessive demand, this leads to a rising price and proliferation of fake commodities. Thus, strict authenticity identification and quality evaluation of agarwood are of great significance. Objective: To establish a simple, rapid and non‐destructive technique for identifying the authenticity of agarwood. Methods: Liquid extraction surface analysis mass spectrometry (LESA‐MS) was firstly proposed to identify the authenticity of 62 agarwood samples without sample preparation. In addition, multivariate statistical models and thin‐layer chromatography (TLC) method were used to analyse and verify the results of LESA‐MS. Results: Representative compounds of agarwood were detected by LESA‐MS. A characteristic 2‐(2‐phenylethyl)chromone compound (m/z 319.1) was treated as a key chemical marker to identify agarwood and its counterfeits rapidly. Several other chromones ions were identified and used as additional evidence for authentic samples. A total of 62 samples were visually discriminated as two groups by principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS‐DA), and the specific characteristic marker was highlighted. Moreover, the qualitative results of the conventional TLC method were in agreement with the LESA‐MS approach. Conclusion: The proposed LESA‐MS method was successfully applied in the direct qualitative analysis of agarwood from different sources. This study indicated great feasibility and practicality of LESA‐MS in the rapid identification of agarwood, and provided a non‐destructive and meaningful preliminary screening tool for the agarwood industry. Agarwood is a highly valuable fragrant resinous wood and has been listed as endangered species in recent years. A new LESA‐MS method was established to rapidly identify authenticity of agarwood without sample preparation, some 2‐(2‐phenylethyl)chromone derivatives were detected and the characteristic 5,6,7,8‐tetrahydro‐2‐(2‐phenylethyl)chromone (m/z 319.1) was the most important compound to differentiate authentic agarwood from counterfeits. The developed LESA‐MS approach was demonstrated to be a simple, automated and non‐destructive technique for direct qualitative determination of agarwood. [ABSTRACT FROM AUTHOR]

Herbal drug‐induced liver injury has been reported worldwide and gained global attention. Thousands of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of herbal medicines and preparations containing pyrrolizidine alkaloids (PAs), which are natural phytotoxins globally distributed. And herbal medicines, such as Gynura japonica, are the current leading cause of PA‐induced HSOS. The present study aimed to reveal the mechanism underlying the hepatotoxicity of seneciphylline (Seph), a main PA in G. japonica. Results showed that Seph induced severe liver injury through apoptosis in mice (70 mg/kg Seph, orally) and primary mouse and human hepatocytes (5–50 μM Seph). Further research uncovered that Seph induced apoptosis by disrupting mitochondrial homeostasis, inducing mitochondrial depolarization, mitochondrial membrane potential (MMP) loss, and cytochrome c (Cyt c) release and activating c‐Jun N‐terminal kinase (JNK). The Seph‐induced apoptosis in hepatocytes could be alleviated by Mdivi‐1 (50 μM, a dynamin‐related protein 1 inhibitor), as well as SP600125 (25 μM, a specific JNK inhibitor) and ZVAD‐fmk (50 μM, a general caspase inhibitor). Moreover, the Seph‐induced MMP loss in hepatocytes was also rescued by Mdivi‐1. In conclusion, Seph induced liver toxicity via activating mitochondrial‐mediated apoptosis in mice and primary hepatocytes. Our results provide further information on Seph detoxification and herbal medicines containing Seph such as G. japonica. Seneciphylline (Seph), a main toxic pyrrolizidine alkaloid in Gynura japonica, induced severe liver injury via activating mitochondrial‐mediated apoptosis in mice and primary hepatocytes. Seph induced apoptosis by disrupting mitochondrial homeostasis, inducing mitochondrial depolarization, MMP loss, Cyt c release etc. The Seph‐induced apoptosis and MMP loss in hepatocytes could be alleviated by Mdivi‐1, a dynamin‐related protein 1 inhibitor, providing further information on Seph detoxification and herbal medicines containing Seph such as G. japonica. [ABSTRACT FROM AUTHOR]

Groundwater plays a major role in the hydrological processes driven by climate change and human activities, particularly in upper mountainous basins. The Jinsha River Basin (JRB) is the uppermost region of the Yangtze River and the largest hydropower production region in China. With the construction of artificial cascade reservoirs increasing in this region, the annual and seasonal flows are changing and affecting the water cycles. Here, we first infer the groundwater storage changes (GWSC), accounting for sediment transport in JRB, by combining the Gravity Recovery and Climate Experiment mission, hydrologic models and in situ data. The results indicate: (1) the average estimation of the GWSC trend, accounting for sediment transport in JRB, is 0.76 ± 0.10 cm/year during the period 2003 to 2015, and the contribution of sediment transport accounts for 15%; (2) precipitation (P), evapotranspiration (ET), soil moisture change, GWSC, and land water storage changes (LWSC) show clear seasonal cycles; the interannual trends of LWSC and GWSC increase, but P, runoff (R), surface water storage change and SMC decrease, and ET remains basically unchanged; (3) the main contributor to the increase in LWSC in JRB is GWSC, and the increased GWSC may be dominated by human activities, such as cascade damming and climate variations (such as snow and glacier melt due to increased temperatures). This study can provide valuable information regarding JRB in China for understanding GWSC patterns and exploring their implications for regional water management. Article impact statement: Changes in groundwater storage when accounting for sediment transport in the Jinsha River Basin are increasing. [ABSTRACT FROM AUTHOR]

Clarification of the quality and biological effect equivalence of traditional Chinese medicines containing multi‐origin species is essential to improve their current quality standards, and also is the core problem to clarify the origins of single herbs with multi‐species in Chinese formulas that will guarantee their clinical application. Huangqin decoction is the typical one of multi‐origin formulas frequently used in traditional Chinese medicine and Kampo medicine. An ultra high performance liquid chromatography with electrospray ionization–tandem mass spectrometry was developed for chemical profiling and marker quantification of Huangqin decoction prepared with two different original types of peony root, white and red peony root. Forty‐seven main peaks in chemical profiling of Huangqin decoction prepared with white and red peony root were identified: nine were from peony root, 20 from baical skullcap root, 17 from licorice root, and one from jujubae fruit. The markers characteristics of the respective types of peony root in Huangqin decoction differ from that in single herbs, especially in terms of monoterpenoids and hydrolysable tannins. Subsequently, 17 representative markers in Huangqin decoction prepared with three types of peony root and their chemical characteristics and content distribution were carried out. [ABSTRACT FROM AUTHOR]

Betaine is an essential nutrient for humans and a source of methyl donors for methionine and S‐adenosylmethionine formation, and it is used as a biomarker for pharmacological activities and to evaluate the quality of Lycium species and common foods. However, because of its special structural features, poor ultraviolet‐chromophore, and high polarity, the existing methods for betaine extraction and quantification cannot provide higher extraction efficiency, better sensitivity, or resolution degree. A simple, fast, and efficient high‐performance liquid chromatography–diode array detector coupled with solid‐phase extraction was adopted for simultaneous separation and quantification of betaine in four types of Lycium species. The results revealed that after degreasing with dichloromethane, extraction with 80% ethanol (pH adjusted to 1.0 with hydrochloric acid), and elution with aluminum oxide (OH− form), the improvement in the average yield rate of betaine was thrice of that of the existing methods. In addition, trigonelline was identified as the interfering substance of betaine for the first time in Lycium species, and betaine and trigonelline were simultaneously separated and quantified. Furthermore, their chemical characteristics and content distribution in different Lycium species were carried out. [ABSTRACT FROM AUTHOR]

The Gravity Recovery and Climate Experiment (GRACE) mission ended its operation in October 2017, and the GRACE Follow‐On mission was launched only in May 2018, leading to approximately 1 year of data gap. Given that GRACE‐type observations are exclusively providing direct estimates of total water storage change (TWSC), it would be very important to bridge the gap between these two missions. Furthermore, for many climate‐related applications, it is also desirable to reconstruct TWSC prior to the GRACE period. In this study, we aim at comparing different data‐driven methods and identifying the more robust alternatives for predicting GRACE‐like gridded TWSC during the gap and reconstructing them to 1992 using climate inputs. To this end, we first develop a methodological framework to compare different methods such as the multiple linear regression (MLR), artificial neural network (ANN), and autoregressive exogenous (ARX) approaches. Second, metrics are developed to measure the robustness of the predictions. Finally, gridded TWSC within 26 regions are predicted and reconstructed using the identified methods. Test computations suggest that the correlation of predicted TWSC maps with observed ones is more than 0.3 higher than TWSC simulated by hydrological models, at the grid scale of 1° resolution. Furthermore, the reconstructed TWSC correctly reproduce the El Nino‐Southern Oscillation (ENSO) signals. In general, while MLR does not perform best in the training process, it is more robust and could thus be a viable approach both for filling the GRACE gap and for reconstructing long‐period TWSC fields globally when combined with statistical decomposition techniques. Key Points: We develop a unified methodological framework to compare viable approaches for reconstructing and predicting globally gridded GRACE fieldsPredicted total water storage change fields fit better to the observations than those simulated by hydrological modelsReconstructed total water storage change correctly reproduces a strong abnormal signal in the tropical river basin during the El Niño period [ABSTRACT FROM AUTHOR]

Notoginsenoside Fc, which is a protopanaxdiol‐type saponin isolated from the leaves of Panax notoginseng, exhibits an exceptional antiplatelet aggregatory effect. To study the modulating effect of gastrointestinal contents on the metabolic profile and pharmacokinetics, pseudo germ‐free rats were used to study the influence of the bacterial community structure on the metabolic profile. Glycosidase activities were measured using the spectrophotometric method. Biotransformations of notoginsenoside Fc in normal and pseudo germ‐free rat intestinal microflora were systematically investigated using ultra high performance liquid chromatography with tandem quadrupole/time‐of‐flight mass spectrometry. Moreover, a liquid chromatography with tandem mass spectrometry method was established for simultaneous determination of the notoginsenoside Fc prototype and its degradation products. Through an in vivo pharmacokinetic study, the pharmacokinetic characteristics were compared between normal rats and pseudo germ‐free rats. During the in vitro biotransformation, seven deglycosylated products were detected and identified after incubation in the intestinal bacteria of normal rats. In pseudo germ‐free rats, glycosidase activities were significantly decreased, and no obvious degradation occurred. In an in vivo study, the systemic exposure was significantly increased 40%, as evidenced by the area under the blood concentration–time curve from time zero to infinity value and half‐life value, which were prolonged more in the pseudo germ‐free group than in normal rats. The results demonstrate that patients who use intestinal bacteria‐metabolized herbs, such as panax notoginseng, should understand the profile of intestinal bacteria to ensure therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Sleep deprivation compromises learning and memory in both humans and animals, and can be reversed by administration of modafinil, a drug promoting wakefulness. Dysfunctional autophagy increases activation of apoptotic cascades, ultimately leading to increased neuronal death, which can be alleviated by autophagy inhibitors. This study aimed to investigate the alleviative effect and mechanism of modafinil on the excessive autophagy occurring in the hippocampus of mice with deficiency of learning and memory induced by sleep deprivation.Experimental Approach: The Morris water maze was used to assess the effects of modafinil on male C57BL/6Slac mice after 48-hr sleep deprivation. The HT-22 hippocampal neuronal cell line was also used. Nissl staining, transmission electron microscope, immunofluorescence, Western blot, transient transfection, and autophagy inducer were used to study the effect and mechanism of modafinil on hippocampal neurons with excessive autophagy and apoptosis.Key Results: Modafinil improved learning and memory in sleep-deprived mice, associated with the inhibition of excessive autophage and apoptosis and an enhanced activation of the PI3K/Akt/mTOR/P70S6K signalling pathway in hippocampal neurons. These effects of modafinil were abolished by rapamycin. In addition, modafinil suppressed the aberrant autophagy and apoptosis induced by rapamycin and reactivated PI3K/Akt/mTOR/P70S6K signals in HT-22 cells.Conclusions and Implications: These results suggested that modafinil alleviated impaired learning and memory of sleep-deprived mice potentially by suppressing excessive autophagy and apoptosis of hippocampal neurons. This novel mechanism may add to our knowledge of modafinil in the clinical treatment of impaired memory caused by sleep loss. [ABSTRACT FROM AUTHOR]

Notoginsenoside Fc, a protopanaxadiol‐type saponin, shows multi‐pharmacological activities. Chemical stability evaluation plays a crucial role in drug development. In this study, the forced degradation behavior of Notoginsenoside Fc was investigated under hydrolytic and oxidative conditions. A specific ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry was developed for the separation, identification, and characterization of the degradation products of Notoginsenoside Fc. Fifty potential degradation products were formed via deglycosylation, dehydration, hydration, isomerization, side‐chain cleaving, oxidation, and superoxidation. Notoginsenoside Fc was subjected to different pH solutions, temperatures, and time periods to assess its stability. A sensitive ultra high performance liquid chromatography‐tandem mass spectrometry was developed for the quantification of Notoginsenoside Fc, notoginsenoside ST‐4, notoginsenoside Ft1, and relative quantification of notoginsenoside Ft2, 20(R)‐notoginsenoside Ft2, notoginsenoside SFt3, and notoginsenoside SFt4. The assay was linear over the concentration range (R2 > 0.997) with the lowest limit of quantification of 0.02 μg/mL for Notoginsenoside Fc, Notoginsenoside ST‐4, and Notoginsenoside Ft1. The intra‐day precision, inter‐day precision, and accuracy of the three analytes were within accepted levels. The degradation kinetics of Notoginsenoside Fc in pH 1 and 3 solutions fits to first‐ and second‐order kinetics, respectively. The degradation of Notoginsenoside Fc is pH‐, temperature‐, and time‐dependent. [ABSTRACT FROM AUTHOR]

Abstract: Quantitative estimates of the groundwater depletion and droughts in the Tigris‐Euphrates Basin (TEB) can be useful for sustainably managing its water resources. Here, data from the Gravity Recovery and Climate Experiment (GRACE) satellite mission are used to infer the monthly changes in the total water storage of the TEB from January 2003 to December 2015. Additionally, the data of altimetry and output from land surface models are used to remove the contributions from lake water changes and other hydrological factors to obtain the total groundwater depletion (TGWD), human‐driven groundwater depletion (HGWD), and climate‐driven groundwater depletion. We conclude that an alarming rate of decrease in the total water storage and the loss of TGWD have an “accelerating” trend, as the trend during 2007 to 2015 was 3.6 times that during 2003 to 2006. Moreover, the HGWD is 116.09 Gt, which accounts for 98% of the TGWD. Finally, the total storage deficit index (TSDI) is derived from the GRACE data to characterize the drought of the TEB. The results show that TSDI agrees well with the actual drought rather than the Palmer drought severity index (PDSI) and that the TEB has been undergoing a severe drought since September 2007 according to both the TSDI and PDSI. The research in this study provides an effective and unique method for understanding the hydrological processes and sustainable use of water resources in regions or countries with little data, which is essential for more efficient, sustainable, and cross‐boundary cooperative water resource management. [ABSTRACT FROM AUTHOR]

Abstract: Picrasma quassioides (D. Don) Benn. is a widely used traditional Chinese medicine for anti‐inflammation and antibiosis. Canthinone and β‐carboline alkaloids are the main characteristic constituents that possess diverse pharmacological effects, such as anti‐inflammatory and anti‐infectious properties. In this study, bioautography in thin‐layer chromatography indicated that the antiradical activity compound may be alkaloids. Then, a simple, fast, and efficient method was established for the separation and purification of two types of alkaloids from P. quassioides by mass‐spectrometry‐directed autopurification system. Eight alkaloids were isolated and purified in this one‐step methodology. Among them, five compounds (3, 95.1%, 58.8 mg; 4, 98.4%, 71.7 mg; 6, 97.8%, 365.4 mg; 7, 97.7%, 172.7 mg; 8, 98.2%, 180.3 mg) were obtained in large amounts with extremely high purities. Then, the antiradical activities of the isolates showed that 4‐methoxy‐5‐hydroxycanthin‐6‐one (6) exhibited obvious 1,1‐diphenyl‐2‐picryl‐hydrazyl free radical scavenging activity with an IC50 value of 84.037 μM. This study offers a new method for the preparation of targeted bioactive alkaloids in P. quassioides. This work also provides a reference for the separation of other targeted chemical components with potential activities from traditional Chinese herbal medicines. [ABSTRACT FROM AUTHOR]

Abstract: In this study, simple ultra‐high performance liquid chromatography coupled with quadrupole time‐of‐flight mass tandem mass spectrometry is used to characterize the absorbed components in rat plasma after the oral administration of saponins from the leaves of Panax notoginseng. Seventeen prototype compounds are structurally characterized. Furthermore, a simple and sensitive liquid chromatography with tandem mass spectrometry method is also used for the simultaneous determination of notoginsenoside Fc, ginsenoside Rb1, ginsenoside Rc, ginsenoside Rb3, ginsenoside Rd, and notoginsenoside Fe in rat plasma within 5 min. After n‐butanol mediated liquid–liquid extraction, all analytes were separated on a C18 column and monitored in negative ion mode. Linearity, sensitivity, intra‐ and inter‐assay precision, accuracy, recovery, matrix effect, and stability were all within acceptable ranges. The validated liquid chromatography with tandem mass spectrometry method is successfully applied to the pharmacokinetic study of saponins from the leaves of Panax notoginseng in rats after oral administration. The results suggest that notoginsenoside Fc and ginsenoside Rb3 showed relatively higher exposure compared with other saponins. All saponins showed a long duration in plasma with a t1/2 longer than 15 h, except notoginsenoside Fe (t1/2 = 2.78 h). This study provides important information about the metabolism of saponins from the leaves of Panax notoginseng, which is useful for completely understanding its mechanism of action. [ABSTRACT FROM AUTHOR]

Psoraleae Fructus is one of the most popular traditional Chinese medicines. Coumarins, flavonoids, and meroterpenes are the main contributors to the biological activity of Psoraleae Fructus. In this study, a new method for the quality control of Psoraleae Fructus was developed, through the quantitative analysis of multicomponents by single marker with diode array detector. Thirteen components, including psoralenoside, isopsoralenoside, psoralen, isopsoralen, psoralidin, neobavaisoflavone, bavachin, corylin, isobavachalcone, corylifol A, bavachinin, bavachalcone, and bakuchiol were rapidly separated and identified within 12 min by the newly developed method. The feasibility and reliability of this method were corroborated. The method was also compared to the external standard method and detection by corona charged aerosol detector. The results of percent difference (%) and cos (θ) have shown that there were no significant differences observed between the quantitative analysis of multicomponents by single marker and external standard method analyses; psoralen and isopsoralen were undetectable with the corona charged aerosol detector due to their but the sensitivity for all the compounds except bakuchiol detected by corona charged aerosol detector are higher than those obtained by diode array detector. In addition, the newly method developed was applied to the quality evaluation of Chinese patent medicines containing Psoraleae Fructus. [ABSTRACT FROM AUTHOR]

The β-carboline alkaloids harmaline and harmine are widely present in hallucinogenic plants with great potential for treating depression, Parkinson's disease, and Alzheimer's disease. The present study was to elucidate metabolic difference of harmaline and harmine in 11 mammalian liver microsomes in order to quantitate species-specific metabolic profiles. Using the probe substrate reaction, the enzymatic activities for 8 CYP450 isozymes of 11 liver microsomes were characterized. Combining ultra performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q/TOF-MS) and ultra performance liquid chromatography combined with electrospray ionization quadrupole tandem mass spectrometry (UPLC-ESI-MS/MS) methods, 18 metabolites for harmaline and 11 for harmine were identified. The metabolism patterns differences of them presented discrepancy in the quality and quantity of metabolites. It was notable that O-sulfate conjugation was detected in all species except sheep. The intrinsic clearance CL int, LM values for the metabolites harmine and harmol in rabbits (37.5 and 42.4 μL/min/mg) were higher than those in other animals, while dogs (16.2 and 16.7 μL/min/mg) and humans (16.0 and 16.3 μL/min/mg) exhibited similar in vitro metabolic clearance. These observations suggested that harmaline and harmine were rapidly metabolized in liver microsomes of rat, mouse, and rabbit; moderately metabolized in human and dog; while weakly metabolized in sheep. Comprehensive analysis of the metabolism indicated that dogs and humans showed considerable similarity in the elimination of parent drugs, metabolic profiles, and catalytic processes. To summarize, these findings illustrated that in vitro studies of harmaline and harmine metabolic profiles in different species are helpful for the proper selection and interpretation of animal models for pharmacological and toxicological evaluation, and will ultimately provide useful guidance for the development of β-carboline alkaloids. Copyright © 2016 John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

A liquid chromatography-electrospray ionization-ion-trap mass spectrometry (MS n) method was established and applied for authentication of Gentiana straminea from the four substitutes, G. tibetica, G. lhassica, G. waltonii and G. robusta, based on chemical profiling of the principal iridoid glucosides aided by a quadrupole time-of-flight mass spectrometry. The fragmentation pathways of the three representative iridoid glucosides, loganic acid, gentiopicroside and sweroside, were investigated by MS n analysis in negative ion mode, which assisted the characterization of analogs detected in the chromatographic profiling of the tested Gentiana species. In total, 25 iridoids were identified or tentatively characterized from G. straminea and four substitutes, in which 7- O-(4′′- O-glucosyl)coumaroyl-loganic acid and 7- O-coumaroyl-loganic acid are diagnostic in G. straminea and can serve as the proposed chemical markers to discriminate it from morphologically similar substitutes. [ABSTRACT FROM AUTHOR]

Plantaginis Semen is commonly used in traditional medicine to treat edema, hypertension, and diabetes. The commercially available Plantaginis Semen in China mainly comes from three species. To clarify the chemical composition and distinct different species of Plantaginis Semen, we established a metabolite profiling method based on ultra high performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry coupled with elevated energy technique. A total of 108 compounds, including phenylethanoid glycosides, flavonoids, guanidine derivatives, terpenoids, organic acids, and fatty acids, were identified from Plantago asiatica L., P. depressa Willd., and P. major L. Results showed significant differences in chemical components among the three species, particularly flavonoids. This study is the first to provide a comprehensive chemical profile of Plantaginis Semen, which could be involved into the quality control, medication guide, and developing new drug of Plantago seeds. [ABSTRACT FROM AUTHOR]

Plants of Erycibe are widely used in traditional Chinese medicine for the treatment of joint pain and rheumatoid arthritis. With the reduction of Erycibe resources in the wild, Porana sinensis has been widely used as a substitute. However, it is important to understand the chemical distinctions between the two kinds of plants and identify their individual chemical markers. In this study, multiwavelength chromatographic fingerprint and precursor ion fingerprint techniques were used in conjunction with chemometric tools to fingerprint and thus differentiate between plant samples. The similar results obtained from different fingerprints prove the reliability of the two fingerprints. Results obtained from principal component analysis and orthogonal projection to latent structures discriminant analysis identified similarities between the chemical components of P. sinensis and plants of Erycibe. However, concentrations of 4-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid were higher in P. sinensis than in plants of Erycibe, suggesting that P. sinensis may be more effective in medical treatments of some diseases than Erycibe. [ABSTRACT FROM AUTHOR]

ABSTRACT Gigantol is a typical bibenzyl compound isolated from Dendrobii Caulis that has been widely used as a medicinal herb in China for the treatment of diabetic cataract, cancer and arteriosclerosis obliterans and as a tonic for stomach nourishment, saliva secretion promotion and fever reduction. However, few studies have been carried out on its in vivo metabolism. In the present study, a rapid and sensitive method based on ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) in positive ion mode was developed and applied to identify the metabolites of gigantol in rat urine after a single oral dose (100 mg/kg). Chromatographic separation was performed on an Acquity UPLC HSS T3 column (100 × 2.1 mm i. d., 1.8 µm) using acetonitrile and 0.1% aqueous formic acid as mobile phases. A total of 11 metabolites were detected and identified as all phase II metabolites. The structures of the metabolites were identified based on the characteristics of their MS, MS2 data and chromatographic retention times. The results showed that glucuronidation is the principal metabolic pathway of gigantol in rats. The newly identified metabolites are useful to understand the mechanism of elimination of gigantol and, in turn, its effectiveness and toxicity. As far as we know, this is the first attempt to investigate the metabolic fate of gigantol in vivo. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT The aerial parts of genus Peganum are officially used in traditional Chinese medicine. The paper aims to establish a high-performance liquid chromatography (HPLC) method for fingerprint analysis and simultaneous determination of three alkaloids and two flavonoids in aerial parts of genus Peganum, and to analyze accumulative difference of secondary metabolites in inter-species, individuals of plants, inter-/intra-population and from different growing seasons. HPLC analysis was performed on a C18 column with gradient elution using 0.1% trifloroacetic acid and acetonitrile as mobile phase and detected at 265 nm, by conventional methodology validation. For fingerprint analysis, the RSDs of relative retention time and relative peak area of the characteristic peaks were within 0.07-0.78 and 0.94-9.09%, respectively. For simultaneous determination of vasicine, harmaline, harmine, deacetylpeganetin and peganetin, all calibration curves showed good linearity ( r > 0.9990) within the test range. The relative standard deviations of precision, repeatability and stability test did not exceed 2.37, 2.68 and 2.67%, respectively. The average recoveries for the five analytes were between 96.47 and 101.20%. HPLC fingerprints play a minor role in authenticating and differentiating the herbs of different species of genus Peganum. However, the secondary metabolites levels of alkaloids and flavonoids in aerial parts of genus Peganum rely on species-, habitat-, and growth season-dependent accumulation. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Sweroside, a major active iridoid in Swertia pseudochinensis Hara, is recognized as an effective agent in the treatment of liver injury. Based on previous reports, the relatively short half-life (64 min) and poor bioavailability (approximately 0.31%) in rats suggested that not only sweroside itself but also its metabolites could be responsible for the observed hepato-protective effect. However, few studies have been carried out on the metabolism of sweroside. Therefore, the present study aimed at identifying the metabolites of sweroside in rat urine after a single oral dose (100 mg/kg). With ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS), the metabolic profile revealed 11 metabolites in rat urine, including phase I, phase II and aglycone-related products. The chemical structures of metabolites were proposed based on accurate mass measurements of protonated or deprotonated molecules and their fragmentation patterns. Our findings showed that the aglycone of sweroside (M05) and its glucuronide conjugate (M06) were principal circulating metabolites in rats. While several other metabolic transformations, occurring via reduction, N-heterocyclization and N-acetylation after deglycosylation, were also observed. Two metabolites (M05 and M06) were isolated from the rat urine for structural elucidation and identifcation of reaction sites. Both M05 and M06 were characterized by 1H, 13C and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. UHPLC/Q-TOF-MS analysis has provided an important analytical platform to gather metabolic profile of sweroside. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

As a final step of the purine metabolism process, xanthine oxidase catalyzes the oxidation of hypoxanthine and xanthine into uric acid. Our research has demonstrated that Erycibe obtusifolia has xanthine oxidase inhibitory properties. The purpose of this paper is to describe a new strategy based on a combination of multiple mass spectrometric platforms and thin-layer chromatography bioautography for effectively screening the xanthine oxidase inhibitory and antioxidant properties of E. obtusifolia. This strategy was accomplished through the following steps. (i) Separate the extract of E. obtusifolia into fractions by an autopurification system controlled by liquid chromatography with mass spectrometry. (ii) Determine the active fractions of E. obtusifolia by thin-layer chromatography bioautography. (iii) Identify the structure of the main active compounds with the information provided by direct analysis in real time mass spectrometry. (iv) Calculate the IC50 value of each compound against xanthine oxidase using high-performance liquid chromatography. Using the caulis of E. obtusifolia as the experimental material, seven target peaks were screened out as xanthine oxidase inhibitors or antioxidants. Our screening strategy allows for rapid analysis of small molecules with almost no sample preparation and can be completed within a week, making it a useful assay to identify unstable compounds and provide the empirical foundation for E. obtusifolia as a natural remedy for gout and oxidative-stress-related diseases. [ABSTRACT FROM AUTHOR]

Pyrrolizidine alkaloids are highly hepatotoxic natural chemicals that produce irreversible chronic and acute hepatotoxic effects on human beings. Purification of large amounts of pyrrolizidine alkaloids is necessary for toxicity studies. In this study, an efficient method for targeted analysis and purification of pyrrolizidine alkaloid cis/ trans isomers from herbal materials was developed for the first time. Targeted analysis of the hepatotoxic pyrrolizidine alkaloids was performed by liquid chromatography with tandem mass spectrometry (precursor ion scan and daughter ion scan), and the purification of pyrrolizidine alkaloids was achieved with a mass-directed auto purification system. The extraction and preparative liquid chromatography conditions were optimized. The developed method was applied to analysis of Gynura japonica (Thunb.) Juel., a herbal medicine traditionally used for detumescence and relieving pain but is potentially hepatotoxic as it contains pyrrolizidine alkaloids. Twelve pyrrolizidine alkaloids (six cis/ trans isomer pairs) were identified with reference compounds or characterized by liquid chromatography with tandem mass spectrometry, and five individual pyrrolizidine alkaloids, including ( E)-seneciphylline, seneciphylline, integerrimine, senecionine, and seneciphyllinine, were prepared from G. japonica roots with high efficiency. The results of this work provide a new technique for the preparation of large amounts of pyrrolizidine alkaloid reference substances, which will also benefit toxicological studies of pyrrolizidine alkaloids and treatments for pyrrolizidine alkaloid-induced toxicity. [ABSTRACT FROM AUTHOR]

RATIONALE 20( S)-Protopanaxadiol (PPD), a dammarane-type triterpenoid sapogenin, acts as the pharmacophore of ginsenosides which are considered as the principal bioactive components in Chinese ginseng. To fully understand the mechanism of action of PPD, it is important to study its metabolic profiles in vivo. METHODS Plasma, urine, fece and bile were collected after administration of PPD formulated in 0.5% aqueous Tween-80 to rats (150 mg/kg). Samples were analyzed by using a sensitive and reliable method based on ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS/MS) in both positive and negative ion mode. The chemical structures of metabolites were elucidated by comparing the retention time, accurate molecular mass, and fragmentation patterns of analytes with those of PPD. RESULTS In total 29 metabolites, including 10 new metabolites (M20-M29), were tentatively identified and characterized. Among them, two metabolites (M3 and M4) were unambiguously identified by matching their retention times and fragmentation patterns with their standards. Principal metabolites, namely, 20, 24-oxide metabolites (M3 and M4), 26/27-carboxylic acid derivatives (M22 and M23) and a glucuronidated product (M28), were found in the rat plasma. CONCLUSIONS The results showed that phase I metabolites are monooxygenation, dioxygenation and oxidative dehydrogenation metabolites, and phase II metabolic pathways were demonstrated to be cysteine conjugation and glucuronidation. The newly identified metabolites are useful to understand the mechanism of elimination of PPD and, in turn, its effectiveness and toxicity. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Gentiopicroside (GPS), the main bioactive component in Gentiana scabra Bge., has attracted our attention owing to its high bioactivity, especially the treatment of hepatobiliary disorders. The aglycone form of GPS, a typical secoiridoid glycoside, is considered to be more readily absorbed than its parent drug. This study aimed to identify and characterize the metabolites after GPS incubated with β-glucosidase in buffer solution at 37°C. Samples of biotransformed solution were collected and analyzed by ultraperformance liquid chromatography (UPLC)/quadrupole-time-of-flight mass spectrometry (Q-TOF MS). A total of four metabolites were detected: two were isolated and elucidated by preparative-HPLC and NMR techniques, and one of those four is reported for the first time. The mass spectral fragmentation pattern and accurate masses of metabolites were established on the basis of UPLC/Q-TOF MS analysis. Structure elucidation of metabolites was achieved by comparing their fragmentation pattern with that of the parent drug. A fairly possible metabolic pathway of GPS by β-glucosidase was proposed. The hepatoprotective activities of metabolites M1 and M2 were investigated and the results showed that their hepatoprotective activities were higher than that of parent drug. Our results provided a meaningful basis for discovering lead compounds from biotransformation related to G. scabra Bge. in traditional Chinese medicine. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Toosendanin (TSN) is a major triterpenoid existing in Melia toosendan, which has been used as a digestive tract parasiticide and insecticide but with serious hepatotoxicity. An ultra-performance liquid chromatography-electrospray ionization-mass spectrometry method was developed for determination of TSN in rat plasma. Plasma samples were separated on Acquity UPLCTM BEH C18 column with acetonitrile and water as flow phase by gradient elution and determined by quadrupole mass spectrometer in negative selective ion monitoring mode. Usolic acid was used as internal standard. The calibration curves were linear over 0.02-3.0 µg/mL for TSN with a lower limit of quantification (LLOQ) of 20 ng/mL in rat plasma. The extraction recoveries of TSN were within 74.3-80.7% with an accuracy of 94.5-108.9%. The intra- and inter-day precision values of the assay at three quality control levels were 8.8-13.8% and <13.9% at LLOQ level, respectively. The method was successfully applied to a pharmacokinetic study of TSN in rats after a single intravenous and oral administration of 2 and 60 mg/kg. The shorter Tmax, higher Vd and Cl of TSN after oral administration indicated that TSN could be absorbed, distributed and eliminated quickly in rats in vivo. The absolute bioavailability of TSN after oral administration was 9.9%. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Phenylethanoid glycosides are a group of phenolic compounds with diverse biological activities such as hypotensive, diuretic, and hypoglycemic effects. In this study, a target profiling analysis approach using ultra-performance liquid chromatography coupled with tandem quadrupole mass spectrometry ( MS) was established on the basis of parent ion scanning for m/ z 161, the characteristic product ion for phenylethanoid glycosides. It was successfully employed to discriminate the chemical composition of phenylethanoid glycosides between Plantaginis Herba and Plantaginis Semen, two medicinal parts of Plantago plants, which are widely used as herbal medicine in China. Totally, 34 phenylethanoid glycosides were characterized and tentatively identified by their retention times, MS, and tandem quadrupole MS ( MS/ MS) data. Combined with chemometrics analysis of principal component analysis and orthogonal projection to latent structural discriminate analysis, eight of them, especially acteoside and plantamajoside, were picked out and contributed to the chemical distinction between Plantaginis Herba and Plantaginis Semen, which might be responsible for the differences in diuretic and hypotensive effects between the two medicinal parts. This new approach for target profiling provides not only a novel idea for specific analysis of active chemical constituents in the same type, but also a promising and reference method for quality evaluation of traditional Chinese medicines. [ABSTRACT FROM AUTHOR]

A rapid, selective and sensitive hydrophilic interaction liquid chromatography (HILIC) coupled with tandem mass spectrometry (MS/MS) method was developed to determine 1-13C- l-methionine in rat serum. Proteins in serum were precipitated using acetonitrile and the supernatant was separated after centrifugation. 1-13C- l-phenylalnine was used as the internal standard. HILIC-tandem mass spectrometry analysis was performed on a hydrophilic interaction silica column (TSK-GEL AMIDE-80) using a linear gradient elution system, acetonitrile−5 m m ammonium acetate containing 0.1% formic acid and multiple reaction monitoring mode for 1-13C- l-methionine and 1-13C- l-phenylalnine. The assay was validated with a linear range between 10 and 150 ng mL−1 ( r ≥ 0.99) and a lower limit of quantification of 10 ng mL−1, calculated with weighted (1/ x2) least squares linear regression. The RSD of intra-day precision was smaller than 3.6% and the inter-day RSD less than 6.5%, while the average recovery was 100.48% with an RSD of accuracy within 2.9%, determined from quality control samples. The HILIC-MS/MS method was fully validated and successfully applied to the in vivo pharmacokinetic study of stable-isotope 1-13C- l-methionine in rats. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Ethanolic extract of the seeds of Plantago asiatica L. showed significant inhibitory activity of angiotensin-converting enzyme (ACE) determined by monitoring the transformation from a substrate hippuryl-histidyl-leucine (HHL) to the product hippuric acid (HA) in vitro using an UPLC-MS method. The bioguided fractionation of the extract resulted in the isolation of four ACE inhibitory active phenylpropanoid glycosides acteoside, isoacteoside, plantainoside D, and plantamajoside with IC50 values of 2.69 mM, 2.46 mM, 2.17 mM, and 2.47 mM, respectively. Their structures were elucidated through the analysis of NMR, UV, IR and MS data. Our study is the first demonstration that Plantago asiatica L. and its major constituents have ACE inhibitory activity in vitro. It is assumed that the identified compounds contribute to the angiotensin-converting enzyme-inhibitory activity of the extract. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme (ACE) plays an important role in the renin-angiotensin system and ACE activity is usually assayed in vitro by monitoring the transformation from a substrate to the product catalyzed by ACE. A rapid and sensitive analysis method or ACE activity by quantifying simultaneously the substrate hippuryl-histidyl-leucine and its product hippuric acid using an ultra-performance liquid chromatography coupled with electrospray ionization-mass spectrometry (UPLC-MS) was first developed and applied to assay the inhibitory activities against ACE of several natural phenolic compounds. The established UPLC-MS method showed obvious advantages over the conventional HPLC analysis in shortened running time (3.5 min), lower limit of detection (5 pg) and limit of quantification (18 pg), and high selectivity aided by MS detection in selected ion monitoring (SIM) mode. Among the six natural products screened, five compounds, caffeic acid, caffeoyl acetate, ferulic acid, chlorogenic acid and resveratrol indicated potent in vitro ACE inhibitory activity with IC50 values of 2.527 ± 0.032, 3.129 ± 0.016, 10.898 ± 0.430, 15.076 ± 1.211 and 6.359 ± 0.086 m m, respectively. A structure-activity relationship estimation suggested that the number and the situation of the hydroxyls on the benzene rings and the acrylic acid groups may play the most predominant role in their ACE inhibitory activity. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]