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[Display omitted] Aconitum pendulum , a member of the Aconitum genus within the Ranunculaceae family, is known for its remarkable anti-inflammatory, anti-tumor, and analgesic properties. However, the application of Aconitum pendulum in traditional medicine is often restricted by its inherent toxicity, necessitating specific processing methods to ensure safe usage. Tibetan medicine utilizes distinctive processing techniques such as the barley wine, Hezitang, and zanba frying systems to render the herb safe for medicinal use. Despite the known pharmacological importance, scant research exists on how these processing methods affect the phytochemical profile of Aconitum pendulum , indicating a necessity for comparative analysis of the resulting concoctions. In this study, we employed 1H nuclear magnetic resonance (1H NMR) spectroscopy and ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) to explore the metabolomic variations among different processed products of Aconitum pendulum. Multivariate data analysis techniques, including pattern recognition, allowed us to investigate the intricacies of the compound profiles. To discover signature chemical markers that can differentiate the various processed products, we conducted paired t-tests and generated heat maps highlighting the detected differences. Our integrated analysis of the 1H NMR and UPLC-Q-TOF-MS data revealed distinct chemical signatures unique to each method of Aconitum pendulum processing. By employing chemometric analysis with variable importance in projection (VIP) scores greater than 1.0, and coupled with the statistical rigor of paired t-tests (P < 0.05), we successfully identified significant chemical markers in various processed products, including ferulic acid (FA), caffeic acid (CA), 3-acetylaconitine (AAC) and benzoylaconitine (BAC). Our findings provide a rapid and robust analysis of the chemical constituencies within raw and processed Aconitum pendulum. The discovery of potential chemical markers through an array of advanced pattern recognition techniques offers a substantial contribution to the pharmaceutical analysis. The results of this research pave the way for future comparative studies and facilitate the recognition of distinctively processed Aconitum pendulum products in traditional medicine. [ABSTRACT FROM AUTHOR]

This study explores efficient bioactive compounds extraction from Fucus vesiculosus (FV) seaweed using Ultrasound-assisted extraction (UAE) and Solid Liquid Extraction (SLE). Varied ultrasound intensities (UI) (58.8, 103.1 and 164.5 kW m−2 for U1, U2 and U3, respectively) were employed, and Peleg's model simulated extraction kinetics, revealing UAE's remarkable 10-min equilibrium contrasted with SLE's 3 h, showcasing UAE's time efficiency. UAE, particularly at U3, yielded significantly higher Total Phenolic Content (TPC) and Uronic Acid Content (UAC) compared to SLE, reaching maximum concentrations of 2.26 ± 0.01 g PGE 100 g−1 DFV and 7.87 ± 0.11 g GAE 100 g−1, respectively. Increased UI enhanced DPPH and ABTS antioxidant activities, while low UI resulted in higher FRAP values. After 20 min of extraction, U3 demonstrated superior DPPH scavenging activity (5.75 ± 0.23 μM TE g−1 DFV), surpassing that of SLE after 20 h of extraction (4.76 ± 0.11 μM TE g−1 DFV). Additionally, U3 displayed elevated ABTS values (8.92 ± 0.33 μM TE g−1 DFV) compared to 6.46 ± 0.41 μM TE g−1 DFV for SLE, with no significant difference observed in FRAP values. These results highlight U3's enhanced antioxidant potential in comparison to SLE. The chromatographic analysis identified six main compounds through UPLC-Q-TOF-MS and HPLC. Higher concentrations of phloroglucinol, gallic acid, catechin, protocatechuic acid, and chlorogenic acid were observed in U3. However, SLE exhibited a higher ferulic acid content. Future research aims to explore phloroglucinol derivatives and FC, contributing to FV' potential applications. [Display omitted] • Fucus vesiculosus emerges as a promising reservoir for diverse bioactive compounds. • UAE swiftly extracts bioactive compounds, exceeding SLE in TPC, FC, and UAC. • UAE delivers potent antioxidants (DPPH, ABTS), comparable FRAP values to SLE. • Peleg's model predicts kinetics, with equilibrium at 3 h (SLE) and 10 min (UAE). • Chromatographic analysis confirms six polyphenols via UPLC-Q-TOF-MS and HPLC. [ABSTRACT FROM AUTHOR]

Zhimu-Huangbo (ZB) herb pair is a common prescription drug used by physicians of all dynasties, and has significant neuroprotective effect, such as the ZB can significantly promote neuronal cell regeneration, repair neuronal damage, and improve cognitive disorders. However, its ingredients are urgently needed to be identified and mechanisms is remained unclear. Using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS), the study of neuroprotective mechanism of Zhimu-Huangbo extract (ZBE) is investigated, and the network pharmacology technology and experimental validation is also performed. Firstly, UPLC-Q-TOF-MS technology was used to characterize the chemical components contained in the ZBE. After that, the TCMSP database and the Swiss Target Prediction method were used to search for potential target genes for ZBE compounds. At the same time, the OMIM and GeneCards disease databases were used to search for Alzheimer's disease (AD) targets and expanded with the GEO database. Then, GO and KEGG enrichment analysis was performed using OECloud tools. Subsequently, the potential mechanism of ZBE therapeutic AD predicted by network pharmacological analysis was experimentally studied and verified in vitro. In the UPLC-Q-TOF-MS analysis of the ZBE, a total of 39 compounds were characterized including Neomangiferin, Oxyberberine, Timosaponin D, Berberine, Timosaponin A-III, Anemarsaponin E, Timosaponin A-I, Smilagenin and so on. A total of 831 potential targets and 13995 AD-related target genes were screened. A further analysis revealed the number of common targets between ZBE and AD is 698. Through GO and KEGG enrichment analysis, we found that ZBE's anti-AD targets were significantly enriched in autophagy and mitochondrial autophagy related pathways. The results of cell experiments also confirmed that ZBE can promote mitochondrial autophagy induced by D-galactose (D-gal) HT22 cells through the PTEN-induced kinase 1/Parkin (PINK1/Parkin) pathway. ZBE can promote autophagy of mitochondria and play a protective role on damaged neurons. [Display omitted] [ABSTRACT FROM AUTHOR]

Radix Ginseng Rubra (RGR), a well-known edible-medicinal herb, has been widely used to attenuate heart failure (HF). However, the active ingredients and mechanism of RGR for attenuating HF have not been illuminated. Thus, the metabolic profile in vivo of RGR was investigated by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and further the compounds identified in serum and heart were employed to search for the potential active compounds and targets via network pharmacology and molecular docking. 41 chemical compounds were identified in RGR aqueous extract. 10 prototypes and 8 metabolites were identified or tentatively characterized in vivo. Additionally, two compounds with 51 corresponding targets had been speculated to improve HF, and the role of ginsenoside Rh 4 (P8) in RGR for attenuating HF by interfering with MAP2K1 and SRC targets was verified by molecular docking. Therefore, the potential active ingredients and targets were expected to be the basis of RGR therapy for HF. [ABSTRACT FROM AUTHOR]

As soluble microbial products (SMPs) can serve as precursors for disinfection by-products (DBPs), the release of SMPs from municipal secondary effluent has the potential to increase the health hazards associated with reused water. Nontargeted identification of DBPs precursors from SMPs in municipal secondary effluent was explored in the present research. The hydrophobic (HPO) fraction that constituted the major portion of the SMPs was 48.0%, and the majority of organic SMPs were composed of low molecular weight (LMW) compounds. The results showed that the HPO fraction with MW < 1 kDa component has the highest disinfection by-product formation potentials (DBPFPs). X-ray photoelectron spectroscopy (XPS) results showed that the HPO fraction with MW < 1 kDa component was mainly composed of O C–OH (40.2%) and amide/peptide N (46.7%) functional groups. This finding was in line with the results showing the highest yields of DBPFPs in terms of HAAs (haloacetic acids) and trichloroacetamide (TCAcAm). Ultra-performance liquid chromatography coupled with tandem quadrupole-time-of-flight mass spectrometry (UPLC-Q-ToF-MS) data revealed that phospholipids, fatty acids, fatty acyls-fatty amides, phosphatidylcholine, glycosides, fatty acid esters, glycolipid, and steroids were the main chemical classes in SMPs. Among these chemical classes, phospholipids containing amino acids structures and fatty acids containing carboxyl functional groups with the maximum abundance could promote the formation of HAAs. This research offers a thorough characterization of SMPs derived from municipal secondary effluent. These results enable the implementation of targeted methods to decrease the formation of DBPs by identifying potential precursors of DBPs. [Display omitted] • AAO-MBR effluent derived SMPs were investigated to identify DBPs precursors. • The HPO fraction with the MW < 1 kDa component has the highest DBPFPs. • O=C-OH and aromatic C were major chemical structures to form C-DBPs. • Amide/peptide N and aromatic N were major chemical structures to form N-DBPs. • Amino acid structure compounds and fatty acids were the major DBPs precursors. [ABSTRACT FROM AUTHOR]

Houttuynia cordata (Thunb.), an important medicinal plant of Northeast India, Korea, and China, is used to treat various ailments and for anticancer research. Knowing its traditional practices, we are interested in the mode-of-action of HCT on HepG2 to co-relate the traditional practice with modern drug therapeutics. UPLC-Q-ToF-Ms analysis of HCT reveals identification of 14 metabolites. Network pharmacology analysis of the 14 compounds showed interaction with 232 different targets with their potential involvement in hepatocellular carcinoma. Whole extracts impart cytotoxicity on variety of cell lines including HepG2. There was a significant morphological alteration in treated HepG2 cells due to impairment of cytoskeletal components like β and γ- tubulin. Arrest at G 1 -S checkpoint was clearly indicated downregulation of Cyclin D1. The root extracts actuated apoptosis in HepG2 as evident from altered mitochondrial membrane potential, Annexin V- FITC, BrdU-PI, AO/EtBr assays, and modulations of apoptotic protein expression but without ROS generation. Whole extracts caused abrogation of epithelial to mesenchymal transition with repression of Snail, N-Cadherin, Vimentin, MMP-9, and upregulation of Pan-Cadherin. Pathway analysis found GSK-3β in Wnt/β-Catenin signaling cascade to be involved through Hepatocellular carcinoma (hsa05225) pathway. The GSK-3β/β-Catenin/PDL-1 signaling was found to be inhibited with the downregulation of pathway components. This was further confirmed by application of EGF, an inducer of the GSK-3β/β-Catenin pathway that neutralized the effect of Houttuynia cordata (Thunb.) root extract on the said pathway. Network pharmacology analysis also confirms the synergy network with botanical-bioactive-target-disease which showed Kaempferol to have the highest degree of association with the said pathway. [Display omitted] • Houttuynia cordata (Thunb.), exerts anti-cancer activity towards hepatic cancer. • UPLC-QTOF-MS/MS analysis identified 14 active compounds. • HepG2 shows anti-apoptotic and proliferative activity with HCT treatment. • HCT exercise apoptosis via GSK-3β/β-Catenin/PDL-1 pathway without ROS production. • Network Pharmacology analysis co-validate the biological outcome. [ABSTRACT FROM AUTHOR]

• Fifteen compounds were identified as chemical markers of LH. • The markers had the best affinity with PTGS2, MAPK1. • LH effectively improved hepatic fibrosis induced in HSC-T6. • LH effectively inhibited the ECM deposition of hepatocytes. • LH could reduce the levels of Fibronectin, Col1a1, Col3a1, etc. Lamiophlomis Herba (LH) is a valuable traditional medicinal plant found on the Qinghai-Tibetan Plateau that promotes blood circulation, removes blood stasis, and has antibacterial and anti-inflammatory properties. The main components of LH are iridoid glycosides, phenethyl alcohol glycosides, flavonoids, and polysaccharides. To investigate the mechanism of the anti-liver fibrosis effects of LH and screen for its bioactive compounds. Screening LH marker components and validating the LH anti-liver fibrosis mechanism. The active ingredients of LH were identified using UPLC-Q-TOF-MS, and HotMap combined with principal components analysis (PCA) was used to screen for marker components. Network pharmacology and molecular docking techniques were used to predict the potential anti-fibrotic targets of LH. Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting were used for experimental validation and mechanistic studies. Fifteen compounds that actively contributed to the cluster were identified as marker compounds. Acteoside, 8-O-acetyl shanzhiside methyl ester (8-O-ASME), Luteolin, Shanzhiside Methyl ester (SME), Loganin, Loganate were the main active components. Network pharmacology and molecular docking studies have shown that LH might improve liver fibrosis, inflammation, and oxidative stress, which might be related to key targets such as PTGS2, MAPK, EGFR, AKT1, SRC, Fn1, Col3a1, Col1a1, and PC-III. The results of ELISA, RT-PCR and western blot experiments showed that Acteoside, 8-O-ASME, Luteolin, SME, Loganin, Loganate, and the LH group could reduce the levels of fibronectin, Col1a1, Col3a1, α-SMA, Col-Ⅳ, LN, and PC-Ⅲ. LH improves liver fibrosis induced by HSC-T6 cells and inhibits the deposition of extracellular matrix (ECM) in hepatocytes, resulting in a decrease in the degree of liver fibrosis and a good anti-liver fibrosis effect. [Display omitted] [ABSTRACT FROM AUTHOR]

Sea buckthorn berries are rich in bioactive compounds and can be used for medicine and food. The variety and drying method used have an important influence on quality. In this study, different sea buckthorn varieties from China were selected and dried with four common drying methods. The total phenolic content (TPC), total flavonoids content (TFC), contents of 12 phenolic compounds and antioxidant capacity in vitro were analyzed. The results showed that the TPC, TFC and antioxidant activity of two wild sea buckthorn berries were higher than those of three cultivated berries, and for the same varieties, measured chemical contents and antioxidant activity of the freeze-dried fruit were significantly higher than those obtained with three conventional drying methods. In addition, forty-one compounds in sea buckthorn berry were identified by UPLC-PDA-Q/TOF-MS, most of which were isorhamnetin derivatives. Multivariate statistical analysis revealed narcissin and isorhamnetin-3-O-glucoside varied significantly in sea buckthorn berries of different varieties and with different drying methods; they were potential quality markers. Strong correlations were found between TPC, gallic acid and antioxidant capacity (p < 0.05). The results revealed how components and antioxidant activity varied in different sea buckthorn, which provides a valuable reference for quality control and further development and utilization of sea buckthorn.

Prepared rhubarb is obtained by steaming raw rhubarb with glutinous rice wine. To explore the chemical material basis and functional mechanism of prepared rhubarb, an ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry coupled with gray correlation analysis statistical method was developed. Finally, 19 compounds in rat plasma were detected after oral administration of prepared rhubarb decoction. It was found that 9 of them were the original form of compounds in prepared rhubarb, and the other 10 were the relative metabolites. Taking bioeffects-time curves into consideration as well, gray correlation analysis were performed. The ranking of these 19 compounds was given out basing on their respective contribution to the drug bioeffect. Rhein glucuronide was eventually found possessing the highest possibility to be the main active ingredient for treatment of noxious heat with blood stasis syndrome.

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.

This study aimed at investigating the mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus(GX) in treating cardiovascular diseases in rats with the syndrome of combined phlegm and stasis. The rat model was established by a high-fat diet, ice-water bath combined with subcutaneous injection of adrenalin hydrochloride, and the syndrome score was determined. The serum samples of rats in the control, model, and GX groups were collected. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to analyze the metabolic profiles of the serum samples. The differential metabolites were screened and identified by partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). The intervention targets of GX-regulated metabolites and their metabolic pathways were searched against MetaboAnalyst. Gene Ontology enrichment was carried out to predict the biological pathways associated with the intervention targets of metabolic pathways. A total of 129 potential biomarkers were detected in the rat model with the syndrome of combined phlegm and stasis via metabolomics, and GX regulated 54 metabolites in several metabolic pathways such as linoleic acid metabolism, sphingolipid metabolism, and tricarboxylic acid cycle. The further screening against MetaboAnalyst showed that GX recovered the levels of nine metabolites associated with cardiovascular diseases with the syndrome of combined phlegm and stasis, which involved 69 targets in the pathways regarding cholesterol metabolism, fatty acid metabolism, inflammatory response, and glucose homeostasis and metabolism. The above-mentioned results suggested that GX can alleviate the symptoms of the rat model of cardiovascular diseases with the syndrome of combined phlegm and stasis by regulating the metabolism of linoleic acid, sphingosine, docosahexaenoic acid, rosemary acid, succinic acid, adenine, L-phenylalanine, L-valine and modulating the biological pathways such as cholesterol metabolism, fatty acid metabolism, inflammatory response, and glucose homeostasis and metabolism.

Febrile seizures (FS) are the most common type of seizures for children. As a commonly used representative cold formula for resuscitation, Zixue Powder (ZP) has shown great efficacy for the treatment of FS in clinic, while its active ingredients and underlying mechanism remain largely unclear. This study aimed to preliminarily elucidate the material basis of ZP and the potential mechanism for the treatment of FS through ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), network pharmacology, and molecular docking. UPLC-Q-TOF-MS was firstly applied to characterize the ingredients in ZP, followed by network pharmacology to explore the potential bioactive ingredients and pathways of ZP against FS. Furthermore, molecular docking technique was employed to verify the binding affinity between the screened active ingredients and targets. As a result, 75 ingredients were identified, containing flavonoids, chromogenic ketones, triterpenes and their saponins, organic acids, etc. Through the current study, we focused on 13 potential active ingredients and 14 key potential anti-FS targets of ZP, such as IL6, STAT3, TNF, and MMP9. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that inflammatory response, EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, and neuroactive ligand-receptor interaction were the main anti-FS signaling pathways. Licochalcones A and B, 26-deoxycimicifugoside, and hederagenin were screened as the main potential active ingredients by molecular docking. In conclusion, this study provides an effective in-depth investigation of the chemical composition, potential bioactive components, and possible anti-FS mechanism of ZP, which lays the foundation for pharmacodynamic studies and clinical applications of ZP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

In this study, based on network pharmacology and molecular docking method, the mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering components was explored, and the efficacy and key targets of Xihuang Pills blood-entering components were experimentally verified by MCF-10A proliferation model of human mammary epithelial cells. In order to clarify the material basis and mechanism of Xihuang Pills in realizing anti-hyperplasia of mammary glands, the blood-entering components of Xihuang Pills were qualitatively analyzed by UPLC-Q-TOF-MS, and 22 blood-entering components were identified. By taking the blood-entering components as the research object, the network pharmacology prediction and molecular docking verification were carried out, and finally, three key targets were screened out, namely JAK1, SRC, and CDK1. In vitro experiments show that Xihuang Pills can inhibit the proliferation of MCF-10A cells, promote the apoptosis of MCF-10A cells, and reduce the expression of JAK1, SRC, and CDK1 targets in cells. To sum up, Xihuang Pills can promote the apoptosis of mammary epithelial cells by regulating the expression of JAK1, SRC, and CDK1 and then play an anti-hyperplasia role, which provides an experimental basis for clarifying the material basis of Xihuang Pills for anti-hyperplasia effect.

Objective To study the prototype components and metabolites of Saposhnikoviae Radixin 9 rats' plasma. Methods UPLC-Q-TOF-MS method was used to identify the components and metabolites of rat plasma. The Eclipse Plus Ci8 column(150 mm ×2. 1.8 μm, Agilent) was used. Themobile phasewas 0.1% acetic acid solution (A)-0.1% acetic acidacetonitrile (B). The gradient elution was used. The flowing rate was 0. 3 ml/min. The injection volume was 3 μl. Results An analytical method for the determination of metabolites of Saposhnikoviae Radix in plasma samples after oral administration. A total of 21 compounds, including 10 prototype components and 11 metabolites, were identified by comparison of their retention time, ion fragmentation information with that of the control plasma, herb extract, and reference compound.. Conclusion The metabolic pathway of the main components of Saposhnikoviae Radixin in rats mainly include hydroxylation, demethylation and glucuonidation,etz. This established method is simple and reliable and provide research basis for revealing the bioactive components of Saposhnikoviae Radix. [ABSTRACT FROM AUTHOR]

Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine (TCM), is mainly used to treat rheumatism and headache diseases. Angelol B is one of the bioactive constituents of APR with significant anti-inflammatory activity. This paper is aimed to illustrate the metabolites of angelol B in vivo. To achieve this objective, a metabolomics approach based on a rapid and accurate UPLC-Q-TOF-MS method was used to detect the metabolites of Angelol B in rat. A gradient elution system (ACN and 0.1% formic acid water) equipped with an Agilent SB-C 18 column (1.8 μm, 2.1 mm × 50 mm) to complete the separation. Scanning area at m/z 100.800 operated on an electrospray ionization (ESI). The data were collected in both positive and negative ion mode and analyzed by the Masslynx 4.1 and SIMCA 13.0 software. A total of 31 metabolites including 20 phase I and 11 phase II. metabolites were identified. Their structure and fragmentation process were deduced based on the MS and MS/MS data. All of thirty-one metabolites are new compounds based on the search of SCI-Finder database. [ABSTRACT FROM AUTHOR]

Qi Bai Granule (QBG), a traditional Chinese medicine formula for the treatment of idiopathic thrombocytopenic purpura, is composed of seven herbs. It is necessary to learn its chemical composition for quality control. In this study, a method for rapid separation and structural identification of the constituents in QBG was established by UPLC-ESI-Q-TOF-MS in negative and positive ion mode. As a result, 112 compounds, such as triterpenoids, flavonoids and monoterpenes were detected. Based on the retention times, accurate masses, fragment ions, related literatures, and/or authentic standards, 107 compounds were unambiguously identified or tentatively characterized. Additionally, 20% monarch, 50% minister, 5% assistant and 24% guide drugs of 112 compounds were detected, which on the whole was consistent with the compatibility of QBG. The results would provide a scientific basis for the quality control, quantitative analysis and further study in vivo or vitro of QBG. [ABSTRACT FROM AUTHOR]

Purpose: Forensic toxicological analyses of drugs and their metabolites in human specimens usually require extractive pretreatment for successful analysis of substances from the matrix. In the present study, a high-throughput method was developed to analyze flunitrazepam, 7-aminoflunitrazepam, 7-acetamidoflunitrazepam, 7-acetamido-3-hydroxyflunitrazepam, and 3-hydroxyflunitrazepam in human plasma and urine samples using a new Monolithic C18 gel-packed SpinTip and ultra-performance liquid chromatography (UPLC)–quadrupole time-of-flight (Q-ToF) mass spectrometry (MS). Methods: Plasma (20 µL) or urine (100 µL) samples spiked with each component were extracted using a Monolithic C18 SPE SpinTip and quantified by UPLC–Q-Tof–MS with positive-ion electrospray ionization (ESI). Results: Good separation, with clear peak shapes of flunitrazepam and its metabolites, was achieved within an analysis time of 6 min, including the extraction time. Recoveries of flunitrazepam and 7-aminoflunitrazepam for plasma and urine samples were 93.5–118% and 97.7–109%, respectively. The regression equations for flunitrazepam and 7-aminoflunitrazepam showed excellent linearity in the range of 0.5–250 ng/mL for plasma and 0.4–500 ng/mL for urine, with detection limits of 0.2–0.5 ng/mL. Intra- and inter-day coefficients of variations for two drugs are smaller than 13.5%. The accuracy of quantitation was 89–110%. Conclusions: The method was successfully applied to determine the level of flunitrazepam and its metabolites in human plasma and urine, respectively, after oral administration to a volunteer. [ABSTRACT FROM AUTHOR]

Hydrolysis and photolysis of bentazone in abiotic aqueous solutions were examined under laboratory conditions. Hydrolysis was studied in different buffer solutions (pH 4.0 ± 0.1, 7.0 ± 0.1, and 9.0 ± 0.1), at different temperatures (15 °C ± 2 °C, 25 °C ± 2 °C, 35 °C ± 2 °C, and 45 °C ± 2 °C), and at different Fe3+ concentrations (1, 5, and 10 mg/L). Photolysis was assessed in different buffer solutions and at different solvent (methanol and ethyl acetate) concentrations (10%, 20%, and 30%) or Fe3+ (1, 5, and 10 mg/L) concentrations and under mercury or xenon light irradiation. Hydrolysis half-lives ranged 46–99 days at three different conditions. Photolysis half-lives ranged 2.3–7.5 h in three different conditions under mercury and xenon irradiation. Hydrolysis and photolysis of bentazone were accelerated by both alkaline conditions and elevated temperatures, and solvents and Fe3+ strongly enhanced bentazone degradation. Photodecomposition was much faster under a mercury lamp than under a xenon lamp. N-methyl bentazone and 6-OH bentazone/8-OH bentazone were identified as degradation products using UPLC-Q-TOF-MS. The data generated from this study could be useful for risk assessment of pesticides in the environment. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Rhizoma Curcumae and Rhizoma Sparganii (RCRS), a celebrated traditional Chinese medicine drug pair, has been used to treat hysteromyoma (HY). Aim of the study We aimed to identify the endogenous biomarkers of RCRS against HY. Materials and methods HY rat model was established by injecting intramuscularly estradiol benzoate and progesterone injection from inner thigh in sequence. Body weight, uterus morphological indexes, immunohistochemistry (IHC) and hematoxylin and eosin (HE) staining experiments were used to evaluate the efficacy of RCRS (The rats were treated with RCRS extract, which was made by soxhlet reflux method. The rats were administrated intragastrically with 2 mL of RCRS extract). UPLC-Q-TOF-MS based metabonomics was adopted to analyze the serum and urine biomarkers from HY rats before and after RCRS treatment. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in rats among the four groups. Results 16 potential biomarkers from serum and 18 potential biomarkers from urine in both positive and negative mass spectrometry detection modes were identified, primarily related to Linoleic acid metabolism and Glyoxylate and dicarboxylate metabolism. RCRS drug pair has therapeutic effects on rats with HY via the regulation of multiple metabolic pathways. Conclusions This study provides a useful method to get insight into the integrated metabonomic mechanism of RCRS drug pair on HY rats. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract The determination of aminopolycarboxylate chelators in environmental samples has remained an analytical challenge due to the structural similarities of these species and their minute concentrations in such matrices. Herein, we report a fast and sensitive technique for the determination of multiple chelator complexes in an aqueous matrix using ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Eight chelators, including non-biodegradable (EDTA, EDTAOH, GEDTA, DPTAOH and DTPA) and biodegradable (EDDS, GLDA, and MGDA) variants were examined after complexation with CuII. The detection of these species using reverse-phase chromatography was compared with that achieved with hydrophilic interaction chromatography based on the corresponding peak resolution and retention time. The effect of varying the composition and pH of the mobile phase on the corresponding peak profiles and intensities for the chelator complexes was also evaluated. The CuII-derivatives of the chelators were individually detected under the optimized operating conditions. Relative to high-performance liquid chromatography equipped with a photodiode array detector, the developed UPLC-Q-TOF-MS technique provides rapid determination of chelator complexes in aqueous matrices with high sensitivity and superior peak resolution. The limit of detection ranged from 1.7–36 nmol L–1, and the limit of quantification ranged from 5.7–120 nmol L–1 for the eight chelator complexes in solution. The coefficients of determination (R 2 ) were 0.962–0.999 for the chelators with an average relative uncertainty of 2.2%. The method was validated using a simulated mixed matrix and river water by standard addition (recovery: 83−100%). Graphical abstract fx1 Highlights • A new technique for the determination of metal-chelator complexes by UPLC-Q-TOF-MS. • Fast separation and better retention achieved using HILIC amide column. • Direct measurement of CuII-chelator complexes without pretreatment steps. • UPLC-Q-TOF-MS method has high sensitivity and peak quality over conventional HPLC-PDA. [ABSTRACT FROM AUTHOR]

Summary: Purpose: To analyze and compare differences in facial skin surface lipids (SSL) between 18‐ to 25‐year‐old males and females. Methods: Ultra‐performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC‐Q‐TOF‐MS) technology was used to measure the facial SSL composition of 18‐ to 25‐year‐old males and females. Measurement results were combined with the orthogonal projections to latent structures discriminant analysis (OPLS‐DA) model for analysis and comparisons, and differences in lipids with significance were selected. Results: There were significant differences in facial SSL composition between 18‐ to 25‐year‐old males and females. Under selected conditions, 37 types of lipids with significant differences were obtained (P ≤ .05). All of them had higher content in females, and primarily included ceramides (Cers), glucosylceramide (GlcCer), phosphatidylserine (PS), phosphatidylcholine (PC), and others. Conclusions: There are significant differences in facial SSL between 18‐ to 25‐year‐old males and females. [ABSTRACT FROM AUTHOR]

Juglans mandshurica Maxim. (JM) is cultivated for timber production, food, and the pharmaceutical industry. Although its leaves (JML) are usually discarded as agricultural waste, they have attracted researchers' attention for reutilization. The present research was therefore carried out to investigate the crop protection potential of JML. First, phenoloxidase-related insecticidal effects were predicted according to in vitro tyrosinase-potentiating property of JML extracts using its 70% and 90% ethanolic extracts from different collection dates (June, July, and August). This was subsequently verified by using diverse bioassay experiments to evaluate its in vivo bioactivity against Plutella xylostella Linnaeus, Aphis gossypii Glover, and Pieris rapae Linne. The results showed that, 90% ethanolic JML extract (20 mg/mL) had the strongest selective anti-feeding activity, with 87.74% and 79.35% deterrence against A. gossypii and P. rapae , respectively. After four days of oral administration, the 70% ethanolic JML extract (50 mg/mL) showed ∼100% corrected mortality in all test insects. Furthermore, regarding contact toxicities, the JML extracts (25 mg/mL) induced ∼71%, 56%, and 82% corrected mortalities against P. xylostella , P. rapae , and A. gossypii , respectively. Among them, JML extracts showed the strongest growth inhibition against P. xylostella (34.12%) and P. rapae (41.23%) after 24 h treatment. Second, the insecticidal mechanism of JML was investigated by targeting the phenoloxidase (PO) of P. xylostella. The insect's PO activity was promoted in vitro with the maximum efficacy of 35.09% from 9 mg/mL of JML extract, and this increasing potential could also be observed in the in vivo evaluation. For instance, after the administration of LC 70 of JML extract till the 4th instar of the insect, stronger PO activity was detected compared to the control group (77.3% vs. 58.0%). The level of L -Dopa, a key intermediate of PO, significantly increased (31.11 μg/mL) in the hemolymph of insects when treated with the LC 70 of JML extract compared with the control group (4.29 μg/mL). The qRT-PCR-mediated mRNA expression analysis confirmed increased PO expression in P. xylostella compared to the control group after JML extract administration. Finally, UPLC-Q-TOF-MS coupled with partial least squared discriminant analysis (PLS-DA) was used to rapidly profile and characterize the 18 compounds as the index ingredients that were related to PO enzymatic activity potentiation or insecticidal effects in the JML extracts. Therefore, our research highlights the potential of J. mandshurica for insecticide development and demonstrates that JML's abnormal promotion of insect PO activity contributes to its toxicity against pests. [Display omitted] • The insecticidal efficacy and abnormal phnoloxidase promotion mechanism of Juglans mandshurica leaves was clarified. • 18 compounds were rapidly and precisely identified as PO targeting insecticidal ingredients in Juglans mandshurica leaves. • The effectiveness of using insect's PO as selective target in botanical insecticide screening was demonstrated. • An effective strategy for rapid exploring and characterization of nature origin insecticidal components was established. [ABSTRACT FROM AUTHOR]

Metapanax delavayi (Franch.) J.Wen & Frodin (Araliaceae), known as "liang wang cha" in China, has been used to treat prostatitis as herbal tea in folk. Recent research suggested that aqueous extract of Metapanax delavayi leaves showed an advantage in anti–benign prostate hyperplasia (BPH) activity, and liangwanoside II was the main component of the active fraction. However, the anti–BPH effect of liangwanosdie II remains to be revealed. This study aims to decipher anti–BPH potential of liangwanoside II. The anti–BPH effect was evaluated by testosterone propionate–induced BPH rats after oral administration of liangwanoside II at the doses of 30, 60 and 120 mg/kg in vivo. Then, the metabolites of liangwanoside II in rats were identified using ultra–performance liquid chromatography coupled with quadrupole tandem time–of–flight mass spectrometry (UPLC–Q–TOF–MS). Finally, the targeted network pharmacology combined with experimental verification were explored for the mechanism elucidation in vivo. Liangwanoside II exhibited an anti–BPH effect through reducing the weight of the prostate, prostate index and serum prostatic acid phosphatase level, and improving the prostate tissue morphology in BPH rats. Further, 16 metabolites of liangwanoside II in vivo were identified by UPLC–Q–TOF–MS analysis, in which the prototype compound and 4 metabolites, such as liangwanoside I and serratagenic acid could be absorbed in the plasma and then penetrate the blood–prostate barrier. Then, followed by the targeted network pharmacology and experimental verification, we found that liangwanoside II and its metabolites could jointly involve in the inhibition of the inflammation reaction and hormone imbalance, thus reducing oxidative stress damage, and restoring the balance between cell proliferation and apoptosis, which contributed to the anti–BPH effect of liangwanoside II. The anti–BPH potential of liangwanoside II was revealed using metabolite profile characterization combined with targeted network pharmacology, providing new insight into the development and utilization of liangwanoside II. [Display omitted] • The advantaged anti–BPH effect of liangwanoside II was first reported. • A total of 16 metabolites of liangwanoside II in the plasma, feces, urines and prostate were firstly identified. • First network pharmacology to predict the anti–BPH mechanism of liangwanoside II and validated by pharmacology. [ABSTRACT FROM AUTHOR]

Although the secondary packing materials do not directly contact the finished drug products, compound migration may still happen between them. To ensure drug quality and safety, extractables and leachables of the packing materials should be analyzed. In this study, 2,6-di-tert-butyl-4-methylphenol (BHT) was first found in the labels for pharmaceutical packaging. For the identification of the compound, a strategy combining high performance liquid chromatography (HPLC), ultra-performance liquid chromatography-quadrupole time-of-flight mass (UPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy was utilized. Afterwards, a effective and sensitive HPLC method for quantification of BHT was developed and validated. Finally, a toxicological risk assessment of BHT was performed to ensure the safety of drugs. • Study on secondary packaging materials for medicine. • Qualitative and quantitative analysis of BHT. • Effects of extracts from secondary packaging materials on drug quality. [ABSTRACT FROM AUTHOR]

[Display omitted] • High-throughput peptidomics was used to identify photooxidation marker peptides in milk. • The peptide m / z + 529.2783 is closely related to milk photooxidation. • Cow breeds, oxygen content and light intensity affected milk photooxidation. Photooxidation is one of the main causes of the deterioration of milk quality during processing and marketing. This study aimed to investigate the variation in peptides after photooxidation using peptidomic techniques, and how cow species, oxygen content, and light intensity affect photooxidation. The different peptides were identified and quantified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Eighteen milk samples were subjected to light treatment. Seven types of peptides were identified as photooxidation markers. Subsequently, the effects of milk variety, oxygen content, and light intensity on photooxidation were studied, and sensory evaluations were performed. Dairy cow breed, oxygen content, and light intensity all affect photooxidation. Sensory evaluation verified that light and oxygen are necessary for the photooxidation of milk. The peptide m / z + 529.2783 (LLDEIKEVV), both in different varieties of milk and in different brands of commercially available milk, showed a large variation in multiplicity, and its content was closely related to oxygen and light. This peptide was not produced in the absence of oxygen and light, and its relative content increased with the duration of light exposure. These results suggest that the peptidomics method is an effective tool for distinguishing between normal and photooxidized milk. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease, characterized by progressive cognitive dysfunction and memory loss. However, the disease-modifying treatments for AD are still lacking. Traditional Chinese herbs, have shown their potentials as novel treatments for complex diseases, such as AD. This study was aimed at investigating the mechanism of action (MOA) of Acanthopanax senticosusin (AS) for treatment of AD. In this study, we firstly identified the chemical constituents in Acanthopanax senticosusin (AS) utilizing ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MS), and next built the drug-target network of these compounds. We also performed the systems pharmacology-based analysis to preliminary explore the MOA of AS against AD. Moreover, we applied the network proximity approach to identify the potential anti-AD components in AS. Finally, experimental validations, including animal behavior test, ELISA and TUNEL staining, were conducted to verify our systems pharmacology-based analysis. 60 chemical constituents in AS were identified via the UPLC-Q-TOF-MS approach. The systems pharmacology-based analysis indicated that AS might exert its therapeutic effects on AD via acetylcholinesterase and apoptosis signaling pathway. To explore the material basis of AS against AD, we further identified 15 potential anti-AD components in AS. Consistently, in vivo experiments demonstrated that AS could protect cholinergic nervous system damage and decrease neuronal apoptosis caused by scopolamine. Overall, this study applied systems pharmacology approach, UPLC-Q-TOF-MS, network analysis, and experimental validation to decipher the potential molecular mechanism of AS against AD. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, a new network pharmacology approach based on the components absorbed into the blood was used to investigate the pharmacodynamic material basis and the pharmacologic mechanism of the Fufang-Xialian-Capsule (FXL) in treating chronic atrophic gastritis (CAG). Initially, we confirmed the components absorbed into the blood by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Then, the network approach, which was based on the results of components absorbed into the blood, was used to analyse the pharmacodynamic material basis and the pharmacologic mechanism of FXL on treating CAG. As a result, 22 absorbed components were found in rat plasma. Given the results of the absorption analysis of the components, eight pathways associated with CAG development were found. The targets linked to these pathways are the drug targets of FXL in CAG treatment. The components associated with these targets are the potential pharmacodynamic material basis and exert synergy in regulating pathways during CAG treatment.

Zingiber species are members of the Zingiberaceae family, and are widely used for medicinal and food purposes. In this study aboveground and root parts of Zingiber mioga and Zingiber officinale were subjected to metabolite profiling by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) in order to characterize them by species and parts and also to measure bioactivities. Both primary and secondary metabolites showed clear discrimination in the PCA score plot and PLS-DA by species and parts. Tetrahydrocurcumin, diarylheptanoid, 8-gingerol, and 8-paradol were discriminating metabolites between Z. mioga and Z. officinale that were present in different quantities. Eleven flavonoids, six amino acids, six organic acids, four fatty acids, and gingerenone A were higher in the aboveground parts than the root parts. Antioxidant activities were measured and were highest in the root part of Z. officinale. The relatively high contents of tetrahydrocurcumin, diarylheptanoid, and galanganol C in the root part of Z. officinale showed highly positive correlation with bioactivities based on correlation assay. On the basis of these results, we can suggest different usages of structurally different parts of Zingiber species as food plants.

To reveal the structural stabilities and transformation mechanism of rhynchophylline (RIN) and isorhynchophylline (IRN), HPLC and UPLC-Q-TOF-MS method were developed for the qualitative and quantitative analysis of the conversion rate. The method was validated for linearity, inter- and intra-day precisions, repeatability and stability. All the quantitative determination method validation results were satisfactory. Under the optimized chromatographic conditions, the effect of various heat temperatures, retention time, and solvent polarities on conversion rate and equilibrium were systematically investigated for the first time. Besides, a model relating the retention yield value and time-temperature was built to predict the t0.5 and Ea of the conversion rate by the Arrhenius equation. The experimental results proved to be in good accordance with the predicted values. Furthermore, UPLC-Q-TOF-MS analysis was performed to verify the transformation mechanism and provide valuable information for stability analysis of the conversion products.

This report presents the application of ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry with positive electrospray ionization, to determine ramipril in human plasma. First, the proteins in human plasma were precipitated using acetonitrile, then the supernatant was extracted by ethyl acetate at pH 3 and finally, the extract was analyzed using a UPLC-QTOF- MS system. The method was validated and the coefficient of determination (R2) was > 0.999, the lower limit of quantification (LLOQ) was 0.5 ng mL-1. Precision, recovery and stability were determined for three different concentrations of ramipril. RSD for this method ranged from 3.3 to 8.6 %. The intra-day mean recovery was from 65.3 to 97.3 %. In addition, the fragmentation of ramipril was studied. Due to high resolution of the spectrometer, it was possible to measure fragment masses accurately and determine their molecular and chemical formulas with high accuracy.

In this study, we analyzed the chemical compositions of Alangium platanifolium (Sieb. et Zucc.) Harms (AP) using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) non-targeted plant metabolomics integration MolNetEnhancer strategy. A total of 75 compounds, including flavonoids, alkaloids, terpenes, C 21 steroids, among others, were identified by comparing accurate mass-to-charge ratios, MS 2 cleavage fragments, retention times, and MolNetenhancer-integrated analytical data, and the cleavage rules of the characteristic compounds were analyzed. A total of 125 potential cervical cancer (CC) therapeutic targets were obtained through Gene Expression Omnibus (GEO) data mining, differential analysis, and database screening. Hub targets were obtained by constructing protein-protein interaction (PPI) networks and CytoNCA topology analysis, including SRC, STAT3, TP53, PIK3R1, MAPK3, and PIK3CA. According to Gene ontology (GO) analysis, AP was primarily against CC by influencing gland development, oxidative stress processes, serine/threonine kinase, and tyrosine kinase activity. Enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the PI3K/AKT and MAPK signaling pathways play a crucial role in AP treatment for CC. The compound-target-pathway (C-T-P) network revealed that quercetin, methylprednisolone, and caudatin may play key roles in the treatment of CC. The results of molecular docking revealed that the core compound could bind significantly to the core target. In this study, the compounds in AP were systematically analyzed qualitatively, and the core components, core targets, and mechanisms of action of AP in the treatment of CC were screened through a combination of network pharmacology tools. Providing a scientific reference for the therapeutic material basis and quality control of AP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 μg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P&lt;0.05) and significant decreases in the levels of 11 substances(P&lt;0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P&lt;0.05) and up-regulated 10 biomarkers(P&lt;0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.

Inflammatory bowel disease is a relapsing inflammatory disease seriously endanger human health. Wedelolactone (WED) is a major active ingredient from Eclipta prostrata (L.) L. and has shown anti-inflammatory effects. However, the mechanism of WED in treating inflammatory colitis remains unknown. We aimed to investigate the mechanisms of WED in treating ulcerative colitis through lipidomic study. Sixty male C57BL/6 mice were exposed to DSS to induce acute colitis. Disease progression was judged by the disease activity index (DAI) and pathological changes of colon tissue. An ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method was performed for colon and plasma lipidomics analyses. Differential metabolites in the three groups were distinguished by univariate and multivariate analysis. WED exerted anti-inflammatory effects representing by body weight and DAI score. Three metabolites were identified in plasma and 20 in colon. According to pathway analysis, the effects of WED on colitis were associated with seven pathways. The glycerophospholipid metabolism and ether lipid metabolism were the primary pathways. The findings provide important insight of the mechanism of WED in treating DSS induced colitis through lipidomic perspective., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Object: This research intended to probe the antibacterial effect and pharmacodynamic substances of Tea-Seed Oil (TSO) through the use of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) analysis, network analysis, and molecular docking. Methods: The major chemical components in the methanol-extracted fractions of TSO were subjected to UPLC-Q-TOF-MS. Network pharmacology and molecular docking techniques were integrated to investigate the core components, targets, and potential mechanisms of action through which the TSO exert their antibacterial properties. To evaluate the inhibitory effects, the minimum inhibitory concentration and diameter of the bacteriostatic circle were calculated for the potential active ingredients and their equal ratios of combinatorial components (ERCC) against Escherichia coli , Staphylococcus aureus , Pseudomonas aeruginosa , and Candida albicans . Moreover, the quantification of the active constituents within TSO was achieved through the utilization of high-performance liquid chromatography (HPLC). Results: The methanol-extracted fractions contained a total of 47 chemical components, predominantly consisting of unsaturated fatty acids and phenolic compounds. The network pharmacology analysis and molecular docking analysis revealed that various components, including gallocatechin, gallic acid, epigallocatechin, theophylline, chlorogenic acid, puerarin, and phlorizin, have the ability to interact with critical core targets such as serine/threonine protein kinase 1 (AKT1), epidermal growth factor receptor (EGFR), a monoclonal antibody to mitogen-activated protein kinase 14 (MAPK14), HSP90AA1, and estrogen receptor 1 (ESR1). Furthermore, these components can modulate the phosphatidylinositol-3-kinase protein kinase B (PI3K-AKT), estrogen, MAPK and interleukin 17 (IL-17) signaling pathways, hereby exerting antibacterial effects. In vitro validation trials have found that seven components, namely gallocatechin, gallic acid, epigallocatechin, theophylline, chlorogenic acid, puerarin, and phloretin, displayed substantial inhibitory effects on E. coli, S. aureus , P. aeruginosa , and C. albicans , and are typically present in tea oil, with a total content ranging from 15.87∼24.91 μg·g -1 . Conclusion: The outcomes of this investigation possess the possibility to expand our knowledge base concerning the utilization of TSO, furnish a theoretical framework for the exploration of antibacterial drugs and cosmetics derived from inherently occurring TSO, and establish a robust groundwork for the advancement and implementations of TOS products within clinical settings., Competing Interests: Y-HZ and Q-ZZ were employed by company Hunan Amazing Grace Biotechnology Co, Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Duan, Zhao, Zhou, Zhou, Fang, Huang, Ma, Wang, Lu, Dai, Li and Li.)

The potential anti-stroke active components in Taohong Siwu Decoction(THSWD) were identified by target cell trapping coupled with ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of active components in THSWD in the treatment of ischemic stroke(IS) was explored by network pharmacology, molecular docking, and experimental validation. The UPLC-Q-TOF-MS technology combined with the UNIFI data analysis platform was used to analyze the composition of the cellular fragmentation fluid after co-incubation of THSWD with target cells. The targets of potential active components and IS were collected by network pharmacology, and the common targets underwent protein-protein interaction(PPI), Gene Ontology(GO), and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analyses. The target cell trapping component-core target-signaling pathway network was constructed, and the active components were molecularly docked to the top targets in the PPI network, followed by pharmacodynamic validation in vitro. Fifteen active components were identified in the target cellular fragmentation fluid, including bicyclic monoterpenes, cyanoglycosides, flavonols, quinoid chalcones, phenylpropanoids, and tannins. As revealed by the analysis of network pharmacology, THSWD presumably regulated PI3K-AKT, FoxO, MAPK, Jak-STAT, VEGF, HIF-1, and other signaling pathways to affect inflammatory cascade reaction, angiogenesis, oxidative stress, pyroptosis, apoptosis, and other pathological processes via paeoniflorin, butylphthalide, dehydrated safflower yellow B, 3,4-dicaffeoylquinic acid, amygdalin, paeoniflorin, and ligusticolactone. Molecular docking and in vitro pharmacodynamic validation revealed that the target cell trapping active components could promote neovascularization in rat brain microvascular endothelial cells(rBMECs) in the oxygen-glucose deprivation/reoxygenation(OGD/R) model. The application of target cell trapping coupled with UPLC-Q-TOF-MS technology can rapidly screen out the potential active components in THSWD. The active components of THSWD can be predicted to intervene in the pathogenesis of IS through network pharmacology, and molecular docking combined with experimental validation can further clarify the efficacy, thus providing a theoretical basis for research ideas on the pharmacodynamic substance basis of traditional Chinese medicine compounds.

Physalis alkekengi L. var. franchetii (Mast.) Makino (PA) is a natural plant which is utilised as a traditional herbal medicine. It has properties that make it effective against inflammation and free radical damage. In the present study, the major constituents of four extraction parts of the fruits of PA (PAF) were investigated by combining ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The mice model of Alzheimer's disease (AD) induced by aluminum chloride (AlCl 3 ) combined with D-galactose (D-gal) was established to comprehend the mechanism behind PAF's anti-AD activity from both behavioural and pathological perspectives. The results showed that four extraction parts of PAF (PAFE) had favorable anti-AD effects and the ethyl acetate (EA) group showed the best activity. UPLC-Q-TOF-MS analysis identified Physalin B, Nobiletin and Caffeic acid as the main anti-AD active constituents in EA extract. This study reveals that PAF can reduce neuroinflammatory damage by inhibiting p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway, which is the theoretical basis for clinical development and utilization of PAF in AD therapy., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Phospholipid molecular species composition of Chinese traditional low-salt fermented fish (Suan yu) inoculated with different starter cultures was investigated. Fifty-six molecular species of phospholipid including 20 species of phosphatidylcholine (PC), 15 species of phosphatidylethanolamine (PE), 6 species of phosphatidylserine (PS), 9 species of lysophosphatidylcholine (LPC), and 6 species of lysophosphatidylethanolamine (LPE) were identified using ultra-performance liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). PC (C16:0–C18:1), PE (C16:0–C22:6), PS (C15:0–C22:6), LPC (C22:6) and LPE (C22:5) were the predominant species. Bioactive polyene phospholipids mainly existed in PE. Furthermore, starter cultures exhibited different influence on phospholipid molecular species. Compared to naturally fermented Suan yu, more molecular species of PE and PS as well as polyene phospholipids were detected in the samples inoculated with Saccharomyces cerevisiae 31 and mixed starter cultures. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic disease with pain, swelling, and limitation in the motion and function of multiple joints thus leading to high disability. Previous studies have shown that flavonoids and saponins are the most abundant and active constituents in Glycyrrhiza, which possess a wide range of pharmacological effects such as anti-inflammatory, antioxidant and anti-bacteria. But the mechanisms of those actions are not entirely clear. In order to clarify the mechanisms of those actions, the pharmacodynamical assessments of extraction of water-soluble components and flavonoids and saponins obtained from Glycyrrhiza were investigated. Combining the pharmacodynamical researches, we found that flavonoids obtained from Glycyrrhiza had more significant therapeutic effects on acute inflammation, chronic inflammation and inflammatory pain than that of extraction of water-soluble components and saponins obtained from Glycyrrhiza. The results indicated that flavonoids are the main medicinal ingredients in Glycyrrhiza. In order to further investigate the mechanism of the action of flavonoids in Glycyrrhiza on treating RA, a urine metabolomics method based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was established to observe the metabolic variations in adjuvant-induced arthritis (AIA) rats and investigate the therapeutic effect of flavonoids in Glycyrrhiza on RA. As a result, twenty potential biomarkers were found by comparison with the model group (MG) and flavonoid treated group (FG). We associated these compounds with related metabolic pathways, the results showed that these biomarkers were mainly associated with purine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism, phenylalanine metabolism, tricarboxylic acid cycle (TCA cycle), pantothenate and coenzyme A (CoA) biosynthesis. The results about the pharmacodynamics and metabolomics provided a theoretical basis for clarifying the mechanism of flavonoids in Glycyrrhiza in the treatment of RA. [ABSTRACT FROM AUTHOR]

Fufang-Xialian-Capsule ( FXL ) is a traditional Chinese medicine ( TCM ) formula which was utilized to treat chronic atrophic gastritis. Despite the chemical constituents have been clarifying by our previous studies, but the metabolism of FXL after oral was still unclear. In order to clarify the mechanism of these absorbed components, a target-group-change (TGC) strategy was utilized to analysis the collected data. This strategy include five steps: (1) acquired the mass spectra data and tandem mass spectra data simultaneously; (2) confirmed the prototype absorbed into blood and the tandem mass behavior of prototype; (3) clarified the potential group change of prototypes after metabolism by Metabolynx XS software; (4) confirmed the target group change acquired by compare the tandem mass behavior of metabolites with their prototypes; (5) inferred the position of group change occurred and metabolic pathways of each prototypes. Based on the TGC strategy, the structure of metabolites and the metabolic pathways of FXL were confirmed. The main group change behaviors on the prototypes after metabolism include demethylation, methylation, hydroxylation and glucuronide conjugation. As the results, there were 33 metabolites transformed from 11 prototypes confirmed, these 11 prototypes include 4 flavones, 5 alkaloids and 2 ginsenosides. All the metabolites could be identified or tentatively characterized according to the structure of metabolites and previous reports. [ABSTRACT FROM AUTHOR]

This study presents a screening strategy for unknown compounds by coupling UPLC-QqQ-MS and UPLC-Q-TOF-MS analyses. Amorfrutins, potential PPARγ agonists in Amorpha fruticosa, were selected as the research target. First, MS/MS analysis of three amorfrutin references (AA, AB, and AC) by Q-TOF revealed the mass-spectrometric fragmentation patterns of amorfrutins, and m/z 225 was recognized as a characteristic and common fragment ion of amorfrutins. Then, unknown amorfrutins were screened in the fruits of A. fruticosa by UPLC-QqQ-MS operating in precursor ion-scan mode, and the product ion was set as m/z 225 for screening potential amorfrutins. According to the high-resolution MS-MS spectral data provided by UPLC-Q-TOF-MS, the molecular formula of potential amorfrutins and their respective characteristic fragments were calculated. Finally, three unknown amorfrutins, namely, amorfrutin D and two new amorfrutins, were identified. As far as we know, this is the first study to rapidly identify unknown compounds by combined application of QqQ-MS precursor ion scan and Q-TOF-MS formula calculation. This research strategy will also be effective for the discovery of other trace natural products and metabolites. [ABSTRACT FROM AUTHOR]

Amorfrutins with a 2-hydroxybenzoic acid core structure are promising natural PPARγ agonists with potent antidiabetic activity. Owing to the complex matrix and low concentration in botanical material, the identification of unknown amorfrutins remains a challenge. In the present study, a combined application of UPLC-Q-TOF-MS and UPLC-QqQ-MS was developed to discover unknown amorfrutins from fruits of Amorpha fruticosa. First, reference compounds of amorfrutin A (AA), amorfrutin B (AB), and 2-carboxy-3,5-dihydroxy-4-geranylbibenzyl (AC) were analyzed using UPLC-Q-TOF-MS to reveal the characteristic fragment ions and the possible neutral loss. Second, the extract of A. fruticosa was separated and screened by UPLC-QqQ-MS using neutral loss scan to find out suspect compounds associated with the specified neutral fragment Δm/z 44. Third, the extract was re-analyzed by UPLC-Q-TOF-MS to obtain the exact mass of quasi-molecular ion and fragment ions of each suspect compound, and to subsequently calculate their corresponding molecular formulas. Finally, according to the molecular formula of suspect compound and its fragment ions and comparing with literature data, structure elucidation of four unidentified amorfrutins was achieved. The results indicated that the combination of QqQ-MS neutral loss scan and Q-TOF-MS molecular formula calculation was proven to be a powerful tool for unknown natural product identification, and this strategy provides an effective solution to discover natural products or metabolites of trace content.ᅟ [ABSTRACT FROM AUTHOR]

Abstract: Xian‐Ling‐Gu‐Bao capsule (XLGB), a well‐known traditional Chinese medicine prescription, has been used for the prevention and treatment of osteoporosis. The safety and efficacy of XLGB have been confirmed based on the principle of evidence‐based medicine. XLGB is usually administered orally, after which its multiple components are brought into contact with intestinal microflora in the alimentary tract and biotransformed. However, investigations on the comprehensive metabolic profile of XLGB are absent. In this study, 12 representative compounds bearing different typical structures (including iridoid glycosides, prenylated flavonol glycosides, prenylated flavonoids, triterpenoid saponins, steroidal saponins, coumarins and monoterpene phenols) were selected and then investigated for their biotransformation in rat intestinal microflora. In addition, the metabolic profile of XLGB in rat intestinal microflora was investigated by ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry. As a result, a total of 87 biotransformation components were identified from incubated solutions of 12 representative compounds and XLGB, which underwent 16 metabolic reactions (including deglycosylation, glycosylation, dehydrogenation, hydrogenation, oxidation, epoxidation, hydroxylation, dehydration, hydration, hydrolysis, methylation, isomerization, cyclization, pyrolysis reaction, amino acid conjugation and nucleophilic addition reaction with NH3). This demonstrated that the deglycosylation reaction by cleavage of the sugar moieties is the main metabolic pathway of a variety of glycosides, including prenylated flavonol glycosides, coumarin glycosides, iridoid glycosides and saponins. In addition, compared with the biotransformation of 12 representative compounds, a different biotransformed fate was observed in the XLGB incubated samples of rat intestinal microflora. It is worth noting that the amino acid conjugation was first discovered in the metabolism of prenylated flavonol glycosides in rat intestinal microflora. [ABSTRACT FROM AUTHOR]

Investigation of flavonoids-rich extract from Scutellaria baicalensis shoots shows that 15 of the 19 flavonoids detected with UPLC-Q-TOF-MS were identified, and it exhibited high antioxidant abilities with IC 50 at 70.81, 35.34 and 33.27 μg/mL in DPPH, ABTS and CAA assays, respectively. An order of antioxidant abilities in scavenging DPPH and ABTS + of eight high content flavonoids in the extract was the same, and it could be well-explained by a preliminary assign-score method we created in structure-activity relationship analyses specific for flavonoids, revealing that double bonds and phenolic hydroxyls on rings A and B are augmentors, and sugar moiety is an attenuator influencing antioxidant capacity but might contribute positively in CAA assays. In addition, three of the eight flavonoids (baicalein, baicalin and scutellarin) made contributions of 58.33%, 60.36% and 51.41% to overall antioxidant activity of the flavonoids-rich extract in DPPH, ABTS and CAA assays, respectively, thus were determined as the primary or marker flavonoids of Scutellaria baicalensis shoots. [ABSTRACT FROM AUTHOR]

Berberrubine, an isoquinoline alkaloid isolated from many medicinal plants, possesses diverse pharmacological activities, including glucose-lowering, lipid-lowering, anti-inflammatory, and anti-tumor effects. This study aimed to investigate the metabolic profile of berberrubine in vivo . Therefore, a rapid and reliable method using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and metabolynx™ software with mass defect filter (MDF) technique was developed. Plasma, bile, urine and feces samples were collected from rats after oral administration of berberrubine with a dose of 30.0 mg/kg and analyzed to characterize the metabolites of berberrubine in vivo for the first time. A total of 57 metabolites were identified, including 54 metabolites in urine, 39 metabolites in plasma, 28 metabolites in bile and 18 metabolites in feces. The results indicated that demethylenation, reduction, hydroxylation, demethylation, glucuronidation, and sulfation were the major metabolic pathways of berberrubine in vivo . [ABSTRACT FROM AUTHOR]

Phospholipids (PLs), as natural additives and nutritional supplements, are recovered from the gum phase during the degumming process of crude vegetable oils. The molecular species of phospholipids recovered from crude soybean (SO), flaxseed (FO) and peanut oil (PO) by different degumming processes, including water (WD), acid (AD), PLA 1 (EDA), PLC (EDC) and PLA 1 -PLC (EDAC) were investigated. According to the PLS-DA model, a total of 30, 38 and 21 characteristic markers were identified using UPLC-Q-TOF-MS in the phospholipids recovered from SO, FO and PO by different degumming processes, respectively. PC (18:2/18:2) and PE (18:2/18:2) were the main phospholipids for WD and AD, LPC (18:2) and LPE (18:2) were the main phospholipids for EDA and EDAC, and PI (16:0/18:2) and PI (16:0/18:1) were served as characteristic phospholipids for EDC. In addition, a lamellar liquid-crystalline phase was observed in the recovered phospholipids, which indicated that the microstructure of phospholipids recovered from crude vegetable oils were significantly influenced by different degumming processes. These differential molecular species of phospholipid products provide useful information to facilitate the potential utilization of phospholipid products as emulsifiers in food and as ingredients in the pharmaceutical industries. [Display omitted] • Molecules of phospholipid were affected by different degumming processes. • Profile of phospholipids recovered from crude flaxseed oil was first reported. • Differential phospholipids were screened as markers by degumming processes. • Microstructures of phospholipids were affected by different degumming processes. [ABSTRACT FROM AUTHOR]

[Display omitted] Tiebangchui, which mainly originates from the dried root of Aconitum pendulum Busch, is an important traditional Tibetan medicine and has long been used for the treatment of various types of cold and pain. However, the excellent pharmacological activities of Tiebangchui are accompanied by high toxicity caused by Aconitum alkaloids. To ensure clinical medication safety, Tiebangchui is only used after processing. Stir-frying with Zanba is an effective and unique processing method in traditional Tibetan medicine, but chemical variations in raw and processed Tiebangchui are rarely reported. In this study, an integrated method combining ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was applied to explore chemical constituent variations, transformation mechanisms, and in situ spatial distributions of metabolites in raw Tiebangchui and its series of processed products. Three important diterpenoid alkaloids were quantified by HPLC. Results revealed visible differences between raw Tiebangchui and its Zanba stir-fried products, and 60 min was demonstrated to be the proper processing time. A total of 64 components were detected, and 32 of them were considered as metabolic markers to distinguish raw Tiebangchui and its processed products stir-fried for different time. Chemical changes were also visualized by DESI-MSI: the contents of aconitine and 3-deoxyaconitine significantly decreased, and those of benzoylaconine, benzoyldeoxyaconine, 16- epi -pyrodeoxyaconitine, and 16- epi -pyroaconitine markedly increased. Transformations from diester-diterpenoid alkaloids to monoester-diterpenoid alkaloids through hydrolysis and pyrolysis were found to be the major detoxication processes during Zanba stir-frying. In summary, UPLC-Q-TOF-MS based metabolomics, DESI-MSI, and quantitative combined approach could be an efficient method to characterize chemical variations in Tiebangchui and its Zanba processed products with different stir-frying time. The wide application of this method would contribute to the process monitoring and safe control of Tiebangchui and other toxic Aconitum medicine. [ABSTRACT FROM AUTHOR]