Effect of Stewing Time on the Small Molecular Metabolites, Free Fatty Acids, and Volatile Flavor Compounds in Chicken Broth.

Chicken broth has a taste of umami, and the stewing time has an important effect on the quality of chicken broth, but there are fewer studies on the control of the stewing time. Based on this, the study was conducted to analyze the effects of different stewing times on the sensory, small molecular metabolites, free fatty acids, and volatile flavor compounds contents in chicken broths by liquid chromatography-quadrupole/time-of-flight mass spectrometry, gas chromatography-mass spectrometry, headspace solid-phase microextraction, and gas chromatography-mass spectrometry. Eighty-nine small molecular metabolites, 15 free fatty acids, and 86 volatile flavor compounds were detected. Palmitic and stearic acids were the more abundant fatty acids, and aldehydes were the main volatile flavor compounds. The study found that chicken broth had the best sensory evaluation, the highest content of taste components, and the richest content of volatile flavor components when the stewing time was 2.5 h. This study investigated the effect of stewing time on the quality of chicken broth to provide scientific and theoretical guidance for developing and utilizing local chicken.

Identification of Biotransformation Products of T-2 Toxin in HepG2 Cells Using LC-Q-TOF MS.

The T-2 toxin (T-2) is a type A trichothecene found in cereals. The formation of metabolites is a frequent cause of mycotoxin-induced toxicity. In this work, the conversion of T-2 during biotransformation reactions in HepG2 cells was evaluated. For this, HepG2 cells were exposed to 30 (IC50/2) and 60 (IC50) nM of T-2 for 0, 1, 2, 3, 6, 8 and 24 h, and the concentrations of T-2 and its metabolites HT-2, T2-triol, T2-tetraol and neosolaniol were determined in both the cell fraction and culture medium through liquid chromatography coupled to high-resolution mass spectrometry-time of flight (LC-Q-TOF MS). Results showed a fast metabolization of T-2 (>90%) during the first 2 h, with HT-2 as its main (>95%) biotransformation product. The cell fraction showed higher levels (p < 0.05) of HT-2 (39.9 ± 2.1 nM) compared to the culture medium (12.53 ± 2.4 nM). This trend was also observed for the identified metabolites. T2-triol reached its maximum concentration (1.7 ± 0.4 nM) at 2 h, and at later times a time-dependent increase in the T2-tetraol and neosolaniol concentrations was observed. The identification of T-2 metabolites shows the need to continue combined toxicity studies of mycotoxins for a correct risk characterization of these natural contaminants.

Effect of different salt additions on the taste and flavor-related compounds in chicken soup.

Chicken soup is popular among consumers because of its delicious taste, strong flavor, and abundant nutritional value. Twenty-four Yunnan local hens were stewed by adding different amounts of NaCl [1.5, 2, 2.5, 3%, m/m, calculated based on chicken carcass weight; chicken: water = 1:2 (m/m)] to study the effect of salt addition on taste- and flavor-related compounds in chicken soup. Sensory evaluation results showed that the 2 and 2.5% NaCl treatment groups had higher scores. Water-soluble small molecule compounds were detected by LC-Q/TOF-MS based metabolomics approach, among which amino acids and their derivatives, nucleic acids, and small peptides were the main components. The concentration of Water-soluble small molecule substances in chicken soup samples with different salt additions showed a clear trend of separation and reached the highest in the 2.5% NaCl treatment group. Volatile flavor compounds in the chicken soup were analyzed by HS-SPME-GC-MS, including aldehydes, and alcohols, and the relative concentration of flavor compounds in the 2.5% salt treatment group was the highest. In summary, the addition of salt could improve the overall flavor of chicken broth, and the optimal salt addition of NaCl in chicken soup is 2.5%.

Identification and Structural Characterization of Degradation Products of Linagliptin by Mass Spectrometry Techniques.

As part of the development and production of pharmaceuticals, the purity of Active Pharmaceutical Ingredients stands as a fundamental parameter that significantly influences the quality, safety, and efficacy of the final drug product. Impurities in Active Pharmaceutical Ingredients are various unwanted substances that can appear during the whole manufacturing process, from raw materials to the final product. These impurities can stem from multiple sources, including starting materials, intermediates, reagents, solvents, and even degradation products resulting from exposure to environmental factors such as heat, light, or moisture. Their presence can potentially compromise the therapeutic effect of the drug, introduce unexpected side effects, or even pose safety risks to patients. This study aims to conduct the forced degradation of linagliptin and subsequently attempt to identify the resulting degradants. The degradation procedures were carried out in accordance with the guidelines of the International Committee for Harmonization. The degradation profile of linagliptin was investigated under various conditions, including acid hydrolysis, alkaline hydrolysis, oxidation, heat, and light exposure, utilizing ultra-performance liquid chromatography connected to a photo array detector. Identification and characterization of the degradation products were achieved using an ultra-performance liquid chromatography coupled with a single quadrupole detector mass spectrometer and also a liquid chromatography coupled with a high-resolution mass spectrometry. The identified degradation products demonstrate that linagliptin is particularly susceptible to degradation when exposed to acid and peroxide. Whereas, no significant degradation effects were observed under alkali, thermolytic, and photolytic conditions.

Uncovering the effect and mechanism of Jiawei Xiaoyao Wan in treating breast cancer complicated with depression based on network pharmacology and experimental analysis.

BACKGROUND: Depression is a clinically common co-morbidity in breast cancer cases that brings negative outcomes on quality of life and potentially survival. Jiawei Xiaoyao Wan (JXW) is widely used in treating breast cancer and depressive disorder, but its potential pharmacological mechanisms remain elusive. PURPOSE: We aimed to explore the dual therapeutic effects and mechanisms of JXW acting on breast cancer complicated with depression (BCCD) by network pharmacology and in vivo experimental verification. METHODS: The chemical constituents of JXW were characterized using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-Q-TOF/MS). The targets related to constituents of JXW were predicted by the TCMSP and Swiss Target Prediction databases, and targets of breast cancer and depression were screened by the GeneCards and OMIM databases. Gene Ontology annotation and KEGG enrichment analysis were performed with the DAVID database. Ultimately, a BCCD mouse model induced by chronic restraint stress (CRS) was used to explore therapeutic effects and mechanisms of JXW against BCCD. The efficacy of JXW in the treatment of BCCD was evaluated based on behavioral tests, tumor volume and weight, and pathological examination. Additionally, the underlying mechanisms were explored by measuring the levels of neurotransmitter and inflammatory factors, as well as detecting the expression of genes or proteins associated with candidate targets and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway through RT-PCR, western blotting, and immunohistochemistry. RESULTS: Totals of 108 components were identified in JXW using LC-Q-TOF/MS. By network pharmacology analysis, 714 compound targets of JXW, 2114 breast cancer targets, 1122 depression targets, and 98 overlapping proteins were obtained. PPI network and KEGG analysis implied that TP53, ESR1, VEGFA, AKT1, IL6, TNF, EGFR and the JAK/STAT pathway might be the potential targets of JXW in treating BCCD. In vivo experiments indicated that JXW significantly ameliorated depressive symptoms and tumor progression in BCCD mice. Further mechanistic studies showed that JXW could reduce the levels of inflammatory factors, increase 5-HT level, and regulate mRNA expression levels of TP53, VEGFA, AKT1, IL6, TNF, and EGFR targets. Moreover, the expression levels of proteins related to the JAK2/STAT3 signaling pathway in BCCD mice were effectively regulated by JXW. CONCLUSION: JXW exerts dual therapeutic effects in a BCCD mouse via multiple targets. The underlying mechanisms might be associated with regulating the levels of neurotransmitter and inflammatory factors; more importantly, the JAK2/STAT3 pathway plays a significant role in this process.

In vivo and in vitro metabolite profiling of nirmatrelvir using LC-Q-ToF-MS/MS along with the in silico approaches for prediction of metabolites and their toxicity.

Nirmatrelvir (NRV), a 3C-like protease or Mpro inhibitor of SARS-CoV-2, is used for the treatment of COVID-19 in adult and paediatric patients. The present study was accomplished to investigate the comprehensive metabolic fate of NRV using in vitro and in vivo models. The in vitro models used for the study were microsomes (human liver microsomes, rat liver microsomes, mouse liver microsomes) and S9 fractions (human liver S9 fractions and rat liver S9 fractions) with the appropriate cofactors, whereas Sprague-Dawley rats were used as the in vivo models. Nirmatrelvir was administered orally to Sprague-Dawley rats, which was followed by the collection of urine, faeces and blood at pre-determined time intervals. Protein precipitation was used as the sample preparation method for all the samples. The samples were then analysed by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-Q-ToF-MS/MS) using an Acquity BEH C18 column with 0.1% formic acid and acetonitrile as the mobile phase. Four metabolites were found to be novel, which were formed via amide hydrolysis, oxidation and hydroxylation. Furthermore, an in silico analysis was performed using Meteor Nexus software to predict the probable metabolic changes of NRV. The toxicity and mutagenicity of NRV and its metabolites were also determined using DEREK Nexus and SARAH Nexus.

Delineation of prototypical degradation mechanism, characterization of unknown degradation impurities by liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry and stability-indicating analytical method of selumetinib.

Selumetinib (SELU) was recently approved by the US Food and Drug Administration (US FDA) in 2020. However, the degradation impurities of SELU have not been characterized or identified to date. The mechanism for impurity formation and the degradation behavior have not been previously studied. This study aims to elucidate the prototypical degradation mechanism of SELU. Furthermore, the degradation impurities have been identified using LC-quadrupole-time-of-flight tandem mass spectrometry and are reported in this article for the first time. In addition, a stability-indicating analytical method (SIAM) has been developed for this drug. Forced degradation studies revealed the degradation of SELU under various stress conditions, including hydrolytic stress (acid and base), oxidative stress, and photolytic stress (ultraviolet and visible). Three degradation impurities were identified. This article presents the first validated SIAM, capable of accurately quantifying SELU in the presence of its degradation impurities. Furthermore, we have proposed the degradation pathway for SELU and its degradation impurities, a first in the field. The developed SIAM can find applications in process development and quality assurance of SELU in both research laboratories and pharmaceutical industries. Moreover, the identified degradation impurities may serve as impurity standards for quality control testing in pharmaceutical industries.

Structural identification of the related substances in phloroglucinol injection by two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry / 药学学报

This study aimed to identify the related substances of phloroglucinol injection by two-dimensional liquid chromatography quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS). The first-dimensional separation was carried out on an HSS T3 (250 mm × 4.6 mm, 5 μm) column by gradient elution using 1.36 g·L-1 potassium dihydrogen phosphate buffer solution (pH adjusted to 3.0 with diluted phosphoric acid) and acetonitrile as the mobile phases. The separated components were then trapped in switch valve tube lines respectively and delivered to the second-dimensional desalting gradient elution which was performed with a BDS C18 (100 mm × 4.6 mm, 2.4 μm) column using 0.1% formic acid and methanol as the mobile phases. After rapid desalting, electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry was used for determining the accurate masses and elemental compositions of the parents and their product ions for both phloroglucinol and its related substance. Structures of the related substances were then figured out by mass spectrometry elucidation, organic reaction mechanism analysis, and/or comparison with reference substances. Under the established analytical conditions, phloroglucinol and its related substances were adequately separated, 17 main related substances were detected and identified in the injection and its stressed samples for the first time. The identification results can provide reference for the quality control of phloroglucinol injection.

Antibacterial activity of Hypericum perforatum L. (St. John's wort) extracts against Gram-positive bacteria and characterisation of its secondary metabolites.

This study aimed to determine the secondary metabolite profiles and antibacterial activity of H. perforatum L extracts against Gram-positive clinical isolates. The plant materials (Sample A and Sample B) were macerated with n-hexane, ethyl acetate and methanol (MeOH). The antibacterial activitiy of plant extracts and routinely used antibiotics were tested against Gram-positive bacteria. The secondary metabolite profiles of Sample A were determined by LC-Q-TOF-MS. The MIC values for n-hexane and ethyl acetate extracts of Sample A were lower than the susceptibility breakpoints of most broad-spectrum antibiotics (e.g. vancomycin, teicoplanin and linezolid) in a certain proportion of Gram-positive bacteria. The n-hexane extract of Sample A showed good antibacterial activity with MICs lower than the susceptibility breakpoint of teicoplanin in 58% of coagulase-negative staphylococci. The n-hexane and ethyl acetate extracts of Sample A had rich phloroglucinol constituents. The n-hexane and ethyl acetate extracts of Sample A could be alternative antibacterial agents against Gram-positive bacteria.

Assessment of Toxic Pyrrolizidine and Tropane Alkaloids in Herbal Teas and Culinary Herbs Using LC-Q-ToF/MS.

Pyrrolizidine alkaloids are secondary metabolites produced by plants as a defense against insects. These can cause acute or chronic toxicity in humans. Therefore, avoiding potential poisoning from the consumption of tea and culinary plants contaminated with pyrrolizidine alkaloids (PAs), pyrrolizidine alkaloids N-oxides (PANOs), and tropane alkaloids (TAs) is important for human health and food safety. Therefore, it is important to determine the levels of these substances with reliable and highly accurate methods. In this study, the PAs, PANOs, and TAs in herbal teas and culinary herbs sold in Turkish markets were identified and their levels were determined. Thus, the general profiles of herbal teas and culinary herbs in Turkey were revealed, and the compliance of the total amounts of PA and TA with the regulations was examined. The identification and quantification of 25 PAs and N-oxides and 2 TAs (atropine and scopolamine) in the samples was performed with a liquid chromatography-quadrupole time-of-flight tandem mass spectrometer (LC-Q-ToF/MS). At least a few of these substances were detected in all of the tested herbal teas and culinary herbs. The total contents of the black tea, green tea, mixed tea, flavored tea, chamomile tea, sage tea, linden tea, fennel tea, rosehip tea, peppermint, and thyme samples ranged from 4.6 ng g-1 to 1054.5 ng g-1. The results obtained shed light on the importance of analyzing the total dehydro PA, PANO, and TA amounts in plant-based products consumed in diets with sensitive and accurate methods, and they highlight the necessity of performing these analyses routinely in terms of food safety.

Changes in bioactive compounds and antioxidant activity of three Amaranthus L. genotypes from a model to household processing.

Amaranthus L. leaves are consumed as vegetables and are a rich source of secondary plant metabolites. The phenolic profiles of the three analyzed genotypes by LC-Q-TOF-MS/MS and HPLC-DAD were characterized by high amounts of hydroxycinnamic glucaric and -isocitric acids. 'Gartenfuchsschwanz' (A. hybridus L.) and 'Red Callaloo' (A. tricolor L.) had similar profiles. 'Gemüse-Amaranth' (A. tricolor L.) had a high amount of caffeoylglucaric acid 4, which was isolated, and afterward identified by NMR. Its antioxidant activity, measured by TEAC, DPPH, and TPC, was similar to 5-caffeoylquinic acid, common in many plant species. The antioxidant activity of Amaranthus L. can be explained rather by their different phenolic- and ascorbic acid concentrations than by their species. Household cooking reduces antioxidant activity due to oxidation processes while leaching into cooking water could be neglected. Amaranthus L. baked into a wheat-dough-matrix showed lower phenolic concentrations, presumably due to the formation of phenol-protein-bounds and thermal degradation.

Anti-inflammatory effect and component analysis of Chaihu Qingwen granules.

ETHNOPHARMACOLOGICAL RELEVANCE: As prevalent acute respiratory condition in clinical practice, acute lung injury has a quick start and severe symptoms which can harm patients physically. Chaihu Qingwen granules (CHQW) is a classic formula for the treatment of respiratory diseases. Clinical observation shows that CHQW has good efficacy in treating colds, coughs, and fevers. AIM OF THE STUDY: The aim of this study was to investigate the anti-inflammatory effect of CHQW on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats and to explore its potential mechanism, as well as to clarify its substance composition. MATERIALS AND METHODS: Male SD rats were randomly divided into the blank group, the model group, the ibuprofen group, the Lianhua Qingwen capsule group and the CHQW group (2, 4 and 8 g/kg, respectively). The LPS-induced acute lung injury (ALI) model in rats was established after pre-administration. The histopathological changes in the lung and the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) and serum of ALI rats were observed. The inflammation-related proteins toll-like receptor 4 (TLR4), inhibitory kappa B alpha (IκBα), phospho-IκBα (p-IκBα), nuclear-factor-kappa B (NF-κB), and NLR family pyrin domain containing 3(NLRP3) expression levels were measured by western blotting analysis and immunohistochemical analysis. The chemical composition of CHQW was identified by liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-Q-TOF-MS). RESULTS: CHQW significantly ameliorated lung tissue pathological injury in LPS-induced ALI rats and decreased the release of inflammatory cytokines (interleukin-1ß, interleukin-17 and tumor necrosis factor-α) in BALF and serum. In addition, CHQW decreased the expression of TLR4, p-IκBα and NF-κB proteins, increased the level of IκBα, regulated the TLR4/NF-κB signaling pathway, and inhibited the activation of NLRP3. The chemical components of CHQW were analyzed by LC-Q-TOF-MS, and a total of 48 components were identified by combining information from the literature, mainly flavonoids, organic acids, lignans, iridoids and phenylethanoid glycosides. CONCLUSION: The results of this study showed that the pretreatment of CHQW had a strong protective effect on LPS-induced ALI in rats, reducing lung tissue lesions and decreasing inflammatory cytokines released in BALF and serum. The protective mechanism of CHQW may be related to the inhibition of the TLR4/NF-κB signaling pathway and NLRP3 activation. The main active ingredients of CHQW are flavonoids, organic acids, lignans, iridoids and phenylethanoid glycosides.

Isomers of the Tomato Glycoalkaloids α-Tomatine and Dehydrotomatine: Relationship to Health Benefits.

High-performance liquid chromatography (HPLC) analysis of three commercial tomatine samples and another isolated from green tomatoes revealed the presence of two small peaks in addition to those associated with the glycoalkaloids dehydrotomatine and α-tomatine. The present study investigated the possible structures of the compounds associated with the two small peaks using HPLC-mass spectrophotometric (MS) methods. Although the two peaks elute much earlier on chromatographic columns than the elution times of the known tomato glycoalkaloids dehydrotomatine and α-tomatine, isolation of the two compounds by preparative chromatography and subsequent analysis by MS shows the two compounds have identical molecular weights, tetrasaccharide side chains, and MS and MS/MS fragmentation patterns to dehydrotomatine and α-tomatine. We suggest the two isolated compounds are isomeric forms of dehydrotomatine and α-tomatine. The analytical data indicate that widely used commercial tomatine preparations and those extracted from green tomatoes and tomato leaves consist of a mixture of α-tomatine, dehydrotomatine, an α-tomatine isomer, and a dehydrotomatine isomer in an approximate ratio of 81:15:4:1, respectively. The significance of the reported health benefits of tomatine and tomatidine is mentioned.

LC-Q-TOF/MS-based Fragmentation Behavior Study and In vitro Metabolites Identification of Nine Benzodiazepines.

BACKGROUND: Benzodiazepines (BZDs) are compounds that contain one diazepine ring and two benzene rings, and are widely used to treat central nervous system diseases. However, drug abuse and BZDs' illegal addition may affect normal life and even lead to grave social harm. As BZDs may be metabolized and eliminated quickly, it is of great theoretical and practical significance to clarify their metabolic profile. OBJECTIVE: In this paper, LC-Q-TOF/MS-based fragmentation behavior has been investigated for nine benzodiazepine drugs available and widely used in clinical treatment (diazepam, nitrazepam, clonazepam, oxazepam, lorazepam, alprazolam, estazolam, triazolam, and midazolam), and their metabolic profile has been studied by using in vitro human liver microsomal incubation. METHODS: A regular human liver microsomal system was used to investigate the potential biotransformation of the nine benzodiazepines in vitro, and an LC-Q/TOF-MS was used to perform fragmentation behavior studies and metabolite identification. RESULTS: As a result, characteristic fragmentation pathway and diagnostic fragment ions of the nine BZDs were analyzed, and 19 metabolites of the 9 benzodiazepines were found and identified, with glucuronidation and hydroxylation considered as their most important metabolic pathways. CONCLUSION: These experimental data add to our knowledge of the nine benzodiazepine drugs and their metabolism study, which could provide useful information and evidence of their in vivo metabolic profile prediction and help promote their monitoring in both clinical use and social/illegal abuse.

Structural identification and comprehensive comparison of saponin-related impurities present in the three different compound glycyrrhizin tablets.

Compound Glycyrrhizin Tablet (CGT) is a glycyrrhizin-containing (monoammonium glycyrrhizate, MAG) preparation, which has been widely used in clinical treatment of chronic liver diseases, eczema, atopic dermatitis and other conditions. However, the impurity profile of CGT has not yet been completely elucidated. In this study, eight main saponin-related impurity compounds were initially isolated and identified. Thereafter, based on the characteristic MS/MS fragmentation pathways analysis of the isolated compounds, a novel strategy for characterization and identification of saponin-related impurities was proposed. Then, a total of 41 saponin-related impurities were identified or tentatively characterized in CGTs. Furthermore, principal component analysis (PCA), Wayne diagram and heatmap analysis revealed that the process-related impurity profile in CGTs from three different manufacturers was significantly different. Overall, our findings provided additional technological support for evaluating saponin-related impurities, thereby laying a solid foundation to develop strategies for future product quality improvement.

LC-Q-TOF-MS/MS detection of food flavonoids: principle, methodology, and applications.

Flavonoids have been attracting increasing research interest because of their multiple health promoting effects. However, many flavonoids with similar structures are present in foods, often at low concentrations, which increases the difficulty of their separation and identification. Liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-Q-TOF-MS/MS) has become one of the most widely used techniques for flavonoid detection. LC-Q-TOF-MS/MS can achieve highly efficient separation by LC; it also provides structural information regarding flavonoids by Q-TOF-MS/MS. This review presents a comprehensive summary of the scientific principles and detailed methodologies (e.g., qualitative determination, quantitative determination, and data processing) of LC-Q-TOF-MS/MS specifically for food flavonoids. It also discusses the recent applications of LC-Q-TOF-MS/MS in determination of flavonoid types and contents in agricultural products, changes in their structures and contents during food processing, and metabolism in vivo after consumption. Moreover, it proposes necessary technological improvements and potential applications. This review would facilitate the scientific understanding of theory and technique of LC-Q-TOF-MS/MS for flavonoid detection, and promote its applications in food and health industry.

A metabolomics study: Could plasma metabolites be a guide for the prevention of tamsulosin side effects?

BACKGROUND: The understanding of precision medicine, which aims for high efficacy and low toxicity in treatments, has gained more importance with omics technologies. In this study, it was aimed to reach new suggestions for low-toxicity treatment by clarifying the relationship between tamsulosin side effects and metabolome profiles. MATERIALS AND METHODS: Plasma samples of control and tamsulosin-treated rats were analyzed by LC-Q-TOF/MS/MS. MS/MS data was processed in XCMS software for the identification of metabolite and metabolic pathway analysis. Data were classified with MATLAB 2019b for multivariate data analysis. 34m/z values were found to be significantly different between the drug and control groups (P≤0.01 and fold analysis≥1.5) and identified by comparing METLIN and HMDB databases. RESULTS: According to multivariate data analysis, α-Linolenic Acid, Thiamine, Retinoic acid, 1.25-Dihydroxyvitamin D3-26.23-Lactone, L-Glutamine, L-Serine, Retinaldehyde, Sphingosine 1-phosphate, L-Lysine, 23S.25-Dihydroxyvitamin D3, Sphinganine, L-Cysteine, Uridine 5'-diphosphate, Calcidiol, L-Tryptophan, L-Alanine levels changed significantly compared to the control group. Differences in the metabolisms of Retinol, Sphingolipid, Alanine-Aspartate-Glutamate, Glutathione, Fatty Acid, Tryptophan, and biosynthesis of Aminoacyl-tRNA, and Unsaturated Fatty Acid have been successfully demonstrated by metabolic pathway analysis. According to our study, vitamin A and D supplements can be recommended to prevent side effects such as asthenia, rhinitis, nasal congestion, dizziness and IFIS in the treatment of tamsulosin. Alteration of aminoacyl-tRNA biosynthesis and sphingolipid metabolism pathways during tamsulosin treatment is effective in the occurrence of nasal congestion. CONCLUSIONS: Our study provides important information for tamsulosin therapy with high efficacy and low side effects in precision medicine.

Alternanthera brasiliana L. extract alleviates carbon tetrachloride-induced liver injury and fibrotic changes in mice: Role of matrix metalloproteinases and TGF-ß/Smad axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Alternanthera brasiliana L. is a flowering plant belonging to the family Amaranthaceae and is popularly known as "penicillin". It is used in folk medicine to treat infections, coughs, wound healing, and inflammatory diseases. AIM OF THE STUDY: We investigated the effect of Alternanthera brasiliana L. leaves hydroalcoholic extract (AB) against oxidative stress, inflammation, and fibrotic changes in an experimental model of carbon tetrachloride (CCl4)-induced liver injury and fibrosis in mice. MATERIALS AND METHODS: Thirty-six male Balb/C mice were randomized into five groups: normal control, AB control, CCl4 control, CCl4 + AB-200 mg/kg, and CCl4 + AB-400 mg/kg. In mice, liver injury was induced by intraperitoneal injection of CCl4 (20% in corn oil, 5 ml/kg body weight) thrice a week for six consecutive weeks. AB extract at two doses (200 mg/kg and 400 mg/kg body weight) was administered orally for six consecutive weeks. Liver injury-related serum markers (ALT, AST, ALP), antioxidants (GSH, GST, SOD, and vitamin C), pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-18, ultrasonographic and histological alterations, proteins of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinase-1 (TIMP-1), nuclear factor-κB (p65) (NF-κB), nod-like receptor protein 3 (NLRP3), and TGF-ß/Smad signaling were accessed. LC-Q-TOF-MS/MS analysis of AB was performed. RESULTS: AB treatment significantly decreased the CCl4-induced rise in serum ALT, AST, and ALP activities and improved the histological alterations. Compared with the CCl4-treated group, treatment with AB significantly restored the hepatic antioxidants and reduced the pro-inflammatory cytokines in the liver. The antioxidant activity of AB may be attributed to its terpenoid constituents, which was confirmed by LC-Q-TOF-MS/MS analysis. The CCl4-induced rise in expression of MMP-2 and MMP-9 and decrease in TIMP-1 were markedly restored in the AB-treated groups. Further findings revealed a significant reduction in the protein levels of phospho-NF-κB (p65), NLRP3, TGF-ß, pSmad2/3, collagen I, and α-smooth muscle actin (α-SMA) in the AB treatment groups. CONCLUSIONS: The hepatoprotective effect of AB may be attributed to the high content of terpenoid compounds and alleviates liver injury and associated fibrotic changes through modulating MMPs, NF-κB (p65), and the TGF-ß/Smad axis.

Nontargeted metabolomics integrated with 1 H NMR and LC-Q-TOF-MS/MS methods to depict a more comprehensive metabolic profile in response to chrysosplenetin and artemisinin co-treatment against artemisinin-sensitive and -resistant Plasmodium berghei K173.

Our previous work revealed mutual and specific metabolites/pathways in artemisinin-sensitive and -resistant Plasmodium berghei K173-infected mice. In this study, we further investigated whether chrysosplenetin, a candidate chemical to prevent artemisinin resistance, can regulate these metabolites/pathways by integrating nontargeted metabolomics with 1 H NMR and LC-Q-TOF-MS/MS spectrum. The nuclear magnetic resonance method generated specifically altered metabolites in response to co-treatment with chrysosplenetin, including: the products of glycolysis such as glucose, pyruvate, lactate and alanine; taurine, closely associated with liver injury; arginine and proline as essential amino acids for parasites; TMAO, a biomarker for dysbacteriosis and renal function; and tyrosine, which is used to generate levodopa and dopamine and may improve the torpor state of mice. Importantly, we noticed that chrysosplenetin might depress the activated glycolysis induced by sensitive parasites, but oppositely promoted the inhibited glycolysis to generate more lactate, which suppresses the proliferation of resistant parasites. Moreover, chrysosplentin possibly disturbs the heme biosynthetic pathway in mitochondria. The MS method yielded changed coenzyme A, phosphatidylcholine and ceramides, closely related to mitochondria ß-oxidation, cell proliferation, differentiation and apoptosis. These two means shared no overlapped metabolites and formed a more broader metabolic map to study the potential mechanisms of chrysosplenetin as a promising artemisinin resistance inhibitor.

Comprehensive oligosaccharide profiling of commercial almond milk, soy milk, and soy flour.

Oligosaccharides are known for several bioactivities on health, however, in sensitive individuals, can cause intestinal discomfort. This study aimed to investigate the oligosaccharide profiles in selected plant-based food products. A quantification method based on high-performance anion-exchange chromatography-pulsed amperometric detection was developed, validated, and used to measure major oligosaccharides. Additional low-abundant oligosaccharides and glycosides were characterized by liquid chromatography-tandem mass spectrometry and glycosidases. The summed concentration of raffinose, stachyose, and verbascose ranged from 0.12-0.19 mg/g in almond milk, 3.6-6.4 mg/g in soy milk, and 74-77 and 4.8-57 mg/g in defatted and full-fat soy four. Over 80 different oligosaccharides were characterized. Novel compounds, 2,3-butanediol glycosides, were identified in almond milk. Low-abundant oligosaccharides represented 25 %, 6 %, and 10 % of total OS in almond milk, soy milk, and soy flour, respectively. The data here are useful to estimate oligosaccharide consumption from dietary intake and facilitate further studies on their bioactivity.