Role of ferroptosis in chronic kidney disease.

Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment. Video Abstract.

Pipette-tip solid-phase extraction coupled with matrix-assisted laser desorption/ionization mass spectrometry enables rapid and high-throughput analysis of antidepressants in rat serum.

Therapeutic drug monitoring is essential for ensuring the efficacy and safety of medications. This study introduces a streamlined approach that combines pipette-tip solid-phase extraction (PT-SPE) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), facilitating rapid and high-throughput monitoring of drug concentrations. As a demonstration, this method was applied to the extraction and quantification of antidepressants in serum. Utilizing Zip-Tip C18, the method enabled the extraction of antidepressants from complex biological matrices in less than 2 min, with the subsequent MALDI-MS analysis yielding results in just 1 min. Optimal extraction recoveries were achieved using a sampling solution at pH 9.0 and a 10 µL ethanol desorption solution containing 0.1% phosphoric acid. For MALDI analysis, 2,5-dihydroxybenzoic acid was identified as the most effective matrix for producing the highest signal intensity. The quantification strategy exhibited robust linearities (R2 ≥ 0.997) and satisfactory limits of quantification, ranging from 0.05 to 0.5 µg/mL for a suite of antidepressants. The application for monitoring dynamic concentration changes of antidepressants in rat serum emphasized the method's efficacy. This strategy offers the advantages of high throughput, minimal sample usage, environmental sustainability, and simplicity, providing ideas and a reference basis for the subsequent development of methods for therapeutic drug monitoring.

Rapid qualitative profiling and quantitative analysis of Juglandis Mandshuricae Cortex and seven flavonoids by ultra-high performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry.

Juglandis Mandshuricae Cortex is the bark of Juglans mandshurica Maxim., which has been used as a folk medicine plant in China and India. In this study, an ultra-high performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry method was developed to clarify and quantify the chemical profiling of Juglandis Mandshuricae Cortex rapidly. A total of 113 compounds were characterized. Among them, seven flavonoids were simultaneously quantified in 15 min, including myricetin, myricetrin, taxifolin, kaempferol, quercetin, quercitrin, and naringenin. The method was validated for accuracy, precision, and the limits of detection and quantification. All calibration curves showed a good linear relationship (r > 0.9990) within test ranges. The intra- and inter-day relative standard deviations were less than 2.16%. Accuracy validation showed that the recovery was between 95.6 and 101.3% with relative standard deviation values below 2.85%. The validated method was successfully applied to determine the contents of seven flavones in Juglandis Mandshuricae Cortex from seven sources and the contents of these places were calculated respectively. This method provides a theoretical basis for further developing the medicinal value of Juglandis Mandshuricae Cortex.

Integrative Analysis of Metabolomic and Transcriptomic Data Reveals Metabolic Alterations in Glioma Patients.

Glioma is a malignant brain tumor. There is growing evidence that its progression involves altered metabolism. This study's objective was to understand how those metabolic perturbations were manifested in plasma and urine. Metabolic signatures in blood and urine were characterized by liquid chromatography-tandem mass spectrometry. The results were linked to gene expression using data from the Gene Expression Omnibus database. Genes and pathways associated with the disease were thus identified. Forty metabolites were identified, which were differentially expressed in the plasma of glioma patients, and 61 were identified in their urine. Twenty-two metabolites and five disturbed pathways were found both in plasma and urine. Twelve metabolites in plasma and three in urine exhibited good diagnostic potential for glioma. Transcriptomic analyses revealed specific changes in the expression of 1437 genes associated with glioma. Seventeen differentially expressed genes were found to be correlated with four of the metabolites. Enrichment analysis indicated that dysregulation of glutamatergic synapse pathway might affect the pathology of glioma. Integration of metabolomics with transcriptomics can provide both a broad picture of novel cancer signatures and preliminary information about the molecular perturbations underlying glioma. These results may suggest promising targets for developing effective therapies.

Chemical profiling of Zilong Jin tablets using ultra high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry.

Zilongjin tablets as a traditional Chinese medicine are widely used for primary lung cancer patients with deficiency of "qi " and "blood " syndrome undergoing chemotherapy. It is a compound preparation that consists of eight herbs. To clarify the chemical profiling of Zilong Jin tablets rapidly, a feasible and accurate strategy was developed by the ultra high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry. According to the accurate mass and fragment ion information provided by high resolution mass spectrometry, the compounds were reasonably identified. In total, 74 compounds were characterized, including 20 flavonoids, 14 quinones, 15 organic acids, 6 phthalide compounds, and 19 other compounds. Among them, 34 major compounds were unambiguously confirmed by comparing with reference standards. This study could provide an important scientific basis for further research on quality control, pharmacokinetics and pharmacodynamics, and clinical application of Zilong Jin tablets.

Combination of high-resolution accurate mass spectrometry and network pharmacology provides a new method for the chemical constituents' study and target prediction in vivo of Garcinia multiflora.

Garcinia multiflora is a kind of evergreen tree which is widely distributed in the south of China. However, few researches focused on the constituents in different parts of G. multiflora as well as their potential targets and pathways in vivo. To clarify the chemical constituents of G. multiflora rapidly and predict the potential targets as well as pathways in vivo that this plant may have effects on, a feasible and accurate strategy was developed to identify the chemical constituents in fruits, leaves, and branches of G. multiflora by ultra-high performance liquid chromatography with Q-Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry. Network pharmacology was then employed and a "compounds-targets-diseases" network was established. Sixty-one compounds including polycyclic polyprenylated acylphloroglucinols, xanthones, and flavonoids were finally identified in different parts of G. multiflora, and the contents of seven constituents were quantified, respectively. On the basis of the network pharmacology analysis results, compounds in this plant were speculated to have potential pharmacodynamic effect on cancer, inflammatory, respiratory diseases, cardiovascular diseases, and metabolic diseases. This research will provide a new method for the advanced study on the pharmacodynamic materials basis of G. multiflora, and offer valuable evidences for medicinal purpose of this plant.

Is the presence of HCMV components in CNS tumors a glioma-specific phenomenon?

BACKGROUND: Human cytomegalovirus (HCMV) has been associated with malignant gliomas. The purpose of the present study was to investigate the presence of HCMV in common non-glial tumors of the central nervous system (CNS) and to determine whether it is a glioma-specific phenomenon. METHODS: Using HCMV-specific immunohistochemical staining, HCMV proteins IE1-72 and pp65 were examined in 65 meningiomas (benign, atypical and malignant), 45 pituitary adenomas, 20 cavernous hemangiomas, and 30 metastatic carcinomas specimens. HCMV DNA was also measured in these tumor tissues and the peripheral blood from patients using nested PCR. RESULTS: In meningioma, IE1-72 was detected in 3.1% (2/65) and pp65 was detected in 4.6% (3/65), whereas no IE1-72 and pp65 were detected in atypical and malignant meningioma. A low level of IE1-72 immunoreactivity 6.7% (2/30) was detected in metastatic carcinoma; pp65 was not detected. No HCMV components were detected in pituitary adenoma and cavernous hemangioma. The results of immunohistochemical staining were confirmed by HCMV-specific PCR. HCMV DNA was not detected in the peripheral blood of the non-glial CNS tumors patients. CONCLUSIONS: Our results demonstrate that the presence of HCMV components is not an entirely glioma-specific phenomenon, and that HCMV is present in a low percentage in some non-glioma CNS tumors. Comparing HCMV-positive non-glial CNS tumors with HCMV-positive gliomas may cast light on the mechanism and role of HCMV in CNS tumors.

Comprehensive characterization and quantification of multiple components in Dan-Huang-Qu-Yu capsule using a multivariate data processing approach based on microwave-assisted extraction with UHPLC and Q Exactive quadrupole-orbitrap high-resolution mass spectrometry.

Dan-Huang-Qu-Yu capsule, a Chinese herbal medicine compound preparation, is widely used for chronic pelvic inflammatory disease. In this study, a rapid, selective, and sensitive microwave-assisted extraction ultra-high-performance liquid chromatography-Q Exactive quadrupole-orbitrap high-resolution mass spectrometry method was developed for analyzing its chemical compositions. A total of 85 compounds, including 22 flavonoids, 8 terpenoids, 5 quinones, 5 phthaleolactone, 23 organic acids, and 22 other compounds were identified from Dan-Huang-Qu-Yu capsule. Among them, 35 major compounds were unambiguously detected by comparing them with reference standards and selected as quality control markers, which were simultaneously determined in Dan-Huang-Qu-Yu capsule. The established method was successfully validated and applied for simultaneous determination of 35 bioactive compounds in Dan-Huang-Qu-Yu capsule from ten sample batches. The quantitative data of the analytes were analyzed by principal component analysis for quality assessment of Dan-Huang-Qu-Yu capsule. Six compounds (e.g., astragaloside IV, salvianolic acid B, ellagic acid, chlorogenic acid, N-butylidenephthalide, and luteolin) were screened out and regarded as chemical markers for quality control of Dan-Huang-Qu-Yu capsule. The established method has been proved to be a novel and useful tool for rapid research of Dan-Huang-Qu-Yu capsule. This research will provide reference for the scientific research of traditional Chinese medicines.

Tissue distribution profiles of multiple major bioactive components in rats after intravenous administration of Xuebijing injection by UHPLC-Q-Orbitrap HRMS.

Xuebijing injection (XBJI) is a traditional Chinese medicine prescription extracted from five Chinese herbs. Hydroxysafflor yellow A, oxypaeoniflorin, ferulic acid and benzoylpaeoniflorin are the main bioactive ingredients of XBJI. This paper presents an application of ultra-high-performance liquid chromatography-Q-exactive hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) to quantify four compounds of XBJI in rats various tissues for tissue distribution studies. The analytes were separated on a Waters Acquity UHPLC® BEH C18 column with a gradient mobile phase consisting of acetonitrile-water (containing 0.1% formic acid) at a flow rate of 0.2 mL/min. Mass spectrometric detection was performed by parallel reaction monitoring via a heated electrospray ionization source under the negative ionization mode. The method was validated in various tissue samples, and has demonstrated great performance for rapidity, accuracy, high sensitivity and selectivity. It was successfully applied to the tissue distribution studies of XBJI after intravenous administration to rats. It was also the first study to investigate the tissue distribution of XBJI in rats and we found that the concentrations of four compounds were high in kidney, liver, stomach and intestine. The clinical use of XBJI should focus on its pharmacodynamics and safety studies in these tissues.

[Quality control of Dandeng Tongnao Ruanjiaonang based on UPLC fingerprint combined with chemical pattern recognition].

To establish the ultra performance liquid chromatography (UPLC) fingerprint of Dandeng Tongnao Ruanjiaonang and conduct a systemic, comprehensive quality evaluation of the drug by combining with a chemical pattern recognition method. In this study, Waters UPLC ultra-high performance liquid chromatography instrument and ACQUITY UPLCHSS T3 chromatographic colum n were employed to perform the separation with acetonitrile-0.1% formic acid aqueous solution as the mobile phase for gradient elution; and the detection wavelength was set at 256 nm to establish the UPLC fingerprint of 10 batches of Dandeng Tongnao Ruanjiaonang. Then, the further quality assessment of the drug was carried out by similarity evaluation, Cluster Analysis(CA), Principal Component Analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Finally, 77 peaks were recognised as common peaks in the fingerprint, and 15 peaks of them were identified using standard references. The similarity value of these 10 batches of drugs was all above 0.960, indicating a relatively stable quality. But minor differences were still discovered between the batches of the drug by CA and PCA. Finally, 6 common peaks were recognised as the quality makers using OPLS-DA method. The analysis method established in this study was scientific, accurate, reliable and simple; fingerprint combined with chemical pattern recognition technique can be used to systematically and comprehensively evaluate the drug quality of Dandeng Tongnao Ruanjiaonang; what's more, it could also provide a reference for the quality control of traditional Chinese medicine and its preparations at the same time.

Qualitative and quantitative determination of YiXinShu Tablet using ultra high performance liquid chromatography with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry.

To clarify and quantify the chemical profile of YiXinShu Tablet rapidly, a feasible and accurate strategy was developed by applying ultra high performance liquid chromatography with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry. A total of 105 components were identified, including 25 phenanthraquinones, 11 lactones, 19 lignans, 24 acids, and 26 other compounds. Among them, 26 major compounds were unambiguously detected by comparing with reference standards. And 19 of these compounds in three batches of YiXinShu Tablet were selected for quantitative determination. (Z)-Ligustilide, salvianic acid A, salvianolic acid A, salvianolic acid B, and rosmarinic acid were abundant in these three batches with contents over 1 mg/g. The established analysis methods were examined to be accurate and feasible. The results show that the ultra high performance liquid chromatography with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry method has a powerful qualitative ability and promising quantitative application.

Chemical profiling and quantification of ShenKang injection, a systematic quality control strategy using ultra high performance liquid chromatography with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry.

ShenKang injection is traditional Chinese medicine used to treat chronic renal failure in China. It is a compound preparation that consists of four herbs: Rhubarb, Salvia miltiorrhiza, Safflower and Radix Astragali. We developed an ultra high pressure liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high resolution accurate mass spectrometry tandem mass spectrometry method to analyze its chemical compositions, and a total of 90 compounds were identified from ShenKang injection. Among them, 19 major compounds were unambiguously detected by comparing with reference standards. Meanwhile, 13 representative compounds selected as quality control markers were simultaneously quantified in ShenKang injection samples. Chromatographic separation was accomplished on a Waters ACQUITY HPLC® HSS C18 column using gradient elution. The method was validated with respect to linearity, sensitivity, accuracy and precision, reproducibility and stability. And the validated method was successfully applied for simultaneous determination of 13 bioactive compounds in ShenKang injection from ten batches of samples by liquid chromatography with mass spectrometry. The results were analyzed by principal components analysis method, and three compounds had a significant relationship with the quality control of ShenKang injection. This research established a rapid and reliable method for the integrating quality control, including qualitation and quantification of ShenKang injection.

Regulation of aerobic glycolysis by long non-coding RNAs in cancer.

As with miRNAs a decade ago, long non-coding RNAs (lncRNAs) are emerging as a new class of RNAs involved in physiological and pathological processes. Recent evidences have shown that lncRNAs play a role in cancer metabolism. The relationship between lncRNAs and aerobic glycolysis provides new strategies for the treatment of cancer. Here we discuss recent findings on the role of lncRNAs in aerobic glycolysis and provide insights into their mechanisms of action. In addition, we explore the potential challenges in using lncRNAs as targets for cancer therapy.

Rapid extraction and determination of 25 bioactive constituents in Alpinia oxyphylla using microwave extraction with ultra high performance liquid chromatography with tandem mass spectrometry.

A novel and rapid microwave extraction and ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of 25 bioactive constituents (including two new constituents) in Fructus Alpinia oxyphylla. The optimized conditions of the microwave extraction was a microwave power of 300 W, extraction temperature of 80°C, solvent-to-solid ratio of 30 mL/g and extraction time of 8 min. Separation was achieved on a Waters ACQUITY UPLC(®) HSS C18 column (2.1 mm× 50 mm, 1.8 µm) using gradient elution with a mobile phase consisting of acetonitrile and 1 mM ammonium acetate at a flow rate of 0.2 mL/min. This is the first report of the simultaneous determination of 25 bioactive constituents in Fructus Alpinia oxyphylla by ultra high performance liquid chromatography with tandem mass spectrometry. The method was validated with good linearity, acceptable precision and accuracy. The validated method was successfully applied to determine the contents of 25 bioactive constituents in Fructus Alpinia oxyphylla from different sources and the analysis results were classified by hierarchical cluster analysis, which indicated the effect of different cultivation regions on the contents of constituents. This study provides powerful and practical guidance in the quality control of Alpinia oxyphylla and lays the foundation for further research of Alpinia oxyphylla.

Determination of the enantiomeric and diastereomeric impurities of RS-glycopyrrolate by capillary electrophoresis using sulfated-ß-cyclodextrin as chiral selectors.

A practical chiral CE method, using sulfated-ß-CD as chiral selector, was developed for the enantioseparation of glycopyrrolate containing two chiral centers. Several parameters affecting the separation were studied, including the nature and concentration of the chiral selectors, BGE pH, buffer type and concentration, separation voltage, and temperature. The separation was carried out in an uncoated fused-silica capillary of (effective length 40 cm) × 50 µm id with a separation voltage of 20 kV using 30 mM sodium phosphate buffer (pH 7.0, adjusted with 1 M sodium hydroxide) containing 2.0% w/v sulfated-ß-CD at 25°C. Finally, the method for determining the enantiomeric impurities of RS-glycopyrrolate was proposed. The method was further validated with respect to its specificity, linearity range, accuracy and precision, LODs, and quantification in the expected range of occurrence for the isomeric impurities (0.1%).

Quantitative prediction of enantioseparation using ß-cyclodextrin derivatives as chiral selectors in capillary electrophoresis.

ß-Cyclodextrin derivatives as chiral selectors are becoming increasingly important for enantioseparations in capillary electrophoresis (CE). Nevertheless, there are some enormous challenges in choosing effective selectors from a variety of compounds, and up to now no systematic quantitative studies for predicting the possibility of enantiomeric separation before CE experiments have been reported. In this paper, in order to resolve previous confusions, we investigated the enantioseparations of ten chiral drugs using a method of combining experiments with theoretical calculations. MMFF, PM3, DFT and ONIOM2 methods were simultaneously utilized during the course of our computer simulations. The results indicated that a specific value of greater than or approximately equal to 6 kJ mol(-1) for the interaction energy difference (ΔΔE) between a pair of enantiomers with a selector is required in order to achieve enantiomeric separation. This discovery offers a meaningful reference to predict enantiomeric separations, so as to design and synthesize some more efficient chiral selectors.

Establishment of a multi-strategy platform for quality control and quality markers screen of Mailuoshutong pill.

Thromboangiitis obliterans (TAO) is a non-atherosclerotic segmental inflammatory occlusive disease with a high recurrence rate, high disability rate, difficulty to cure, and poor prognosis. It has been clinically proven that Mailuoshutong pill (MLSTP) is an effective traditional Chinese medicine for treating TAO. As MLSTP contains hundreds of chemical components, the quality control of which is a challenge in the development of reliable quality evaluation metrics. This study aimed to evaluate the quality uniformity of MLSTP by establishing a multi-strategy platform. In the present study, the key targets and signaling pathways of MLSTP treating TAO were predicted by network pharmacology. It was further shown by in vivo validation experiments that MLSTP exerted therapeutic effects on TAO by modulating the PI3K-AKT signaling pathway, VEGF signaling pathway, and HIF-1 signaling pathway. In addition, UPLC fingerprints of MLSTP were established and screened for potential Q-markers of MLSTP in combination with network pharmacology results. Six components, including chlorogenic acid, liquiritin, paeoniflorin, calycosin-7-glucoside, berberine, and formononetin, were selected as potential quality markers (Q-markers) in MLSTP. Finally, the quantitative analysis of multi-components by single marker (QAMS) method was established to quantitatively analyze the six potential Q-markers, and the results were consistent with those obtained by the external standard method (ESM). Taken together, the multi-strategy platform established in this study would be conducive to the Q-markers screening and quality control of MLSTP, improving the quality standard of MLSTP and providing favorable assurance for the clinical management of TAO.

Matrix-assisted laser desorption/ionization mass spectrometry for the rapid and high throughput analysis of betaine and trigonelline in Lycium chinense Mill. and trigonelline in coffee.

A rapid, simple, effective, and green method for the determination of betaine and trigonelline from Lycium chinense Mill. (LCM) and the quantification of the trigonelline in coffee was proposed and validated by matrix-assisted laser desorption ionization time-of-flight mass spectrometric (MALDI-TOF MS) detection. Due to without chromatographic separation, the method greatly shortened the detection time. The detection of betaine and trigonelline concentration showed good linearity in the range of 1-100 µg/mL and 0.01-100 µg/mL, with correlation coefficients r2 = 0.9962 and 0.9946, respectively. The good reproducibility and reliability of the method were demonstrated by excellent intraday and interday precisions with RSD <8.3%, and the recovery of betaine and trigonelline ranged from 92.2% to 116.0%. Analysis of LCM and coffee extracts (raw, light-roasted, and dark-roasted coffee beans) gave results in agreement with the literature. The method appeared as a fast and reliable alternative method for routine Lycium chinense and coffee analysis.

XueBiJing injection improves the symptoms of sepsis-induced acute lung injury by mitigating oxidative stress and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: XBJ injection is approved by the China Food and Drug Administration for the adjunctive treatment of sepsis, and it is derived from the traditional Chinese medicine (TCM) prescription XuefuZhuyu Decoction. It consists of five Chinese herbal extracts: Carthamus tinctorius, Paeonia lactiflora, Salvia miltiorrhiza, Conioselinum anthriscoides 'Chuanxiong' and Angelica sinensis. AIM OF THE STUDY: The purpose of this study was to explore the relationship between ferroptosis and acute septic lung injury, and to evaluate the improvement effect of XBJ injection on acute lung injury in sepsis. MATERIALS AND METHODS: Acute lung injury was induced in rats by cecum ligation and puncture, and these rats were treated with XBJ injection. Oxidative stress and inflammation levels were assessed in serum and lung tissue, and tissue samples were collected for histological and protein analyses. To illustrate the mechanism of the improvement effect of XBJ on acute lung injury in sepsis, serum lipidomics was carried out to investigate whether XBJ prevents oxidative stress-induced lipid metabolism disorders. Furthermore, protein expression of ferroptosis-related genes was also examined. RESULTS: XBJ was shown to be effective in alleviating sepsis-induced ALI. XBJ also improves sepsis-induced acute lung injury by reducing lipid peroxidation and inflammation and modulating ferroptosis pathways. Specifically, compared with the sham group, XBJ downregulated the levels of Fe2+, MDA and GSSG, and reversed the decrease in the levels of GSH and GSH/GSSH in lung tissue. Metabolic pathways such as glycerophospholipid metabolism, phospholipid metabolism, and lipid metabolism associated with ferroptosis were obtained by lipidomic analysis of differential lipid metabolite enrichment, suggesting that ferroptosis occurs in septic rats, and that XBJ inhibits ferroptosis and thereby improves sepsis-induced ALI. Furthermore, XBJ optimises iron metabolism and lipid oxide metabolism by regulating the expression of a series of proteins that are closely related to ferroptosis, such as GPX4, ACSL4, x-CT, and FTH1. CONCLUSIONS: Our findings, initially, indicated that XBJ ameliorates sepsis-induced ALI by reducing oxidative stress and ferroptosis, revealing a previously unrecognised mechanism by which XBJ ameliorates sepsis-induced ALI.

Unraveling spatial metabolome of the aerial and underground parts of Scutellaria baicalensis by matrix-assisted laser desorption/ionization mass spectrometry imaging.

BACKGROUND: Scutellaria baicalensis Georgi, a traditional Chinese medicine, is clinically applied mainly as the dried root of Scutellaria baicalensis, and the aerial parts of Scutellaria baicalensis, its stems and leaves, are often consumed as "Scutellaria baicalensis tea" to clear heat, dry dampness, reduce fire and detoxify, while few comparative analyses of the spatial metabolome of the aerial and underground parts of Scutellaria baicalensis have been carried out in current research. METHODS: In this work, Matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) was used to visualize the spatial imaging of the root, stem, and leaf of Scutellaria baicalensis at a high resolution of 10 µm, respectively, investigating the spatial distribution of the different secondary metabolites in the aerial and underground parts of Scutellaria baicalensis. RESULTS: In the present results, various metabolites, such as flavonoid glycosides, flavonoid metabolites, and phenolic acids, were systematically characterized in Scutellaria baicalensis root, stem, and leaf. Nine glycosides, 18 flavonoids, one organic acid, and four other metabolites in Scutellaria baicalensis root; nine glycosides, nine flavonoids, one organic acid in Scutellaria baicalensis stem; and seven flavonoids and seven glycosides in Scutellaria baicalensis leaf were visualized by MALDI-MSI. In the underground part of Scutellaria baicalensis, baicalein, wogonin, baicalin, wogonoside, and chrysin were widely distributed, while there was less spatial location in the aerial parts. Moreover, scutellarein, carthamidin/isocarthamidin, scutellarin, carthamidin/isocarthamidin-7-O-glucuronide had a high distribution in the aerial parts of Scutellaria baicalensis. In addition, the biosynthetic pathways involved in the biosynthesis of significant flavonoid metabolites in aerial and underground parts of Scutellaria baicalensis were successfully localized and visualized. CONCLUSIONS: MALDI-MSI offers a favorable approach for investigating the spatial distribution and effective utilization of metabolites of Scutellaria baicalensis. The detailed spatial chemical information can not only improve our understanding of the biosynthesis pathways of flavonoid metabolites, but more importantly, suggest that we need to fully exert the overall medicinal value of Scutellaria baicalensis, strengthening the reuse and development of the resources of Scutellaria baicalensis aboveground parts.