Biosynthesis of Nanoparticles with Green Tea for Inhibition of ß-Amyloid Fibrillation Coupled with Ligands Analysis.

Background: Inhibition of amyloid ß protein fragment (Aß) aggregation is considered to be one of the most effective strategies for the treatment of Alzheimer's disease. (-)-Epigallocatechin-3-gallate (EGCG) has been found to be effective in this regard; however, owing to its low bioavailability, nanodelivery is recommended for practical applications. Compared to chemical reduction methods, biosynthesis avoids possible biotoxicity and cumbersome preparation processes. Materials and Methods: The interaction between EGCG and Aß42 was simulated by molecular docking, and green tea-conjugated gold nanoparticles (GT-Au NPs) and EGCG-Au NPs were synthesized using EGCG-enriched green tea and EGCG solutions, respectively. Surface active molecules of the particles were identified and analyzed using various liquid chromatography-tandem triple quadrupole mass spectrometry methods. ThT fluorescence assay, circular dichroism, and TEM were used to investigate the effect of synthesized particles on the inhibition of Aß42 aggregation. Results: EGCG as well as apigenin, quercetin, baicalin, and glutathione were identified as capping ligands stabilized on the surface of GT-Au NPs. They more or less inhibited Aß42 aggregation or promoted fibril disaggregation, with EGCG being the most effective, which bound to Aß42 through hydrogen bonding, hydrophobic interactions, etc. resulting in 39.86% and 88.50% inhibition of aggregation and disaggregation effects, respectively. EGCG-Au NPs were not as effective as free EGCG, whereas multiple thiols and polyphenols in green tea accelerated and optimized heavy metal detoxification. The synthesized GT-Au NPs conferred the efficacy of diverse ligands to the particles, with inhibition of aggregation and disaggregation effects of 54.69% and 88.75%, respectively, while increasing the yield, enhancing water solubility, and decreasing cost. Conclusion: Biosynthesis of nanoparticles using green tea is a promising simple and economical drug-carrying approach to confer multiple pharmacophore molecules to Au NPs. This could be used to design new drug candidates to treat Alzheimer's disease.

Identification of plant microRNAs using convolutional neural network.

MicroRNAs (miRNAs) are of significance in tuning and buffering gene expression. Despite abundant analysis tools that have been developed in the last two decades, plant miRNA identification from next-generation sequencing (NGS) data remains challenging. Here, we show that we can train a convolutional neural network to accurately identify plant miRNAs from NGS data. Based on our methods, we also present a user-friendly pure Java-based software package called Small RNA-related Intelligent and Convenient Analysis Tools (SRICATs). SRICATs encompasses all the necessary steps for plant miRNA analysis. Our results indicate that SRICATs outperforms currently popular software tools on the test data from five plant species. For non-commercial users, SRICATs is freely available at https://sourceforge.net/projects/sricats.

Preparation of magnetic amphiphilic resin microspheres via the one-step polymerization method and extraction of four glucocorticoids for HPLC-MS analysis.

Amphiphilic materials can be used for sample preparation of chromatography or mass spectrometry. Amphiphilic materials with magnetic properties in combination with magnetic suction devices allow for automated sample preparation. However, conventional synthesis methods are cumbersome and not suitable for the mass production of the material. In this study, a micro-suspension polymerization method was developed to synthesize magnetic amphiphilic resin microspheres (MARMs), providing new ideas for the preparation of amphiphilic microspheres. MARMs with particle sizes ranging from 3 to 6 µm were successfully prepared, with BET surface area up to 653.2 m2/g. A magnetic solid-phase extraction method based on MARM-5 was developed for the extraction of four glucocorticoids including Cortisone, Hydrocortisone, Cortodoxone, and Corticosterone. This method had a very short adsorption time of 0.5 min and a total extraction time of only 13 min. The limit of detection for the four glucocorticoids ranged from 0.22 to 0.82 ng/L. There was a good linear relationship between sample concentration and peak area in the range of 25∼500 ng/L. Relative recovery of 98 %∼108 % and internal standard normalized matrix effect factors of 95∼114 % were obtained, and the relative standard deviation was between 2.3 % and 6.3 %. The MARMs would be used as excellent solid extraction material for glucocorticoids.

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

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

A Ribulose-5-phosphate Shunt from the Calvin-Benson Cycle to Methylerythritol Phosphate Pathway for Enhancing Photosynthetic Terpenoid Production.

Cyanobacteria are attractive hosts for photosynthetic terpenoid production, using CO2 as the sole carbon source. Although the methylerythritol phosphate (MEP) pathway is superior to the mevalonate pathway for cyanobacterial terpenoid synthesis, the first reaction of the MEP pathway, which is catalyzed by 1-deoxy-d-xylulose-5-phosphate (DXP) synthase, involves complex regulation and carbon loss. Here, we constructed a direct route linking ribulose-5-phosphate (Ru5P) in the Calvin-Benson (CB) cycle with DXP in the MEP pathway in a cyanobacterium to increase the terpenoid yield from CO2 and bypass the DXS-targeted regulations. By employing the adaptive laboratory evolution, we identified new RibB variants including RibB 90-92del with a high activity of synthesizing DXP from Ru5P. These RibB variants were introduced into Synechococcus elongatus, resulting in the significantly increased photosynthetic production of isopentenol. The 13C tracer experiments demonstrated a direct carbon flow from Ru5P in the CB cycle to the MEP pathway; thus, this direct route was denoted as the Ru5P shunt. The strain harboring the Ru5P shunt produced 105.2 mg L-1 of isopentenol with an average rate of 17.5 mg L-1 d-1 under continuous light conditions, which is higher than those ever reported for five-carbon alcohol production by photoautotrophic microorganisms. Utilization of the Ru5P shunt in cyanobacterial cells also improved the pinene production, which demonstrates that this shunt can be used to enhance the photosynthetic production of diverse terpenoids.

Rapid classification and identification of chemical compositions of Pu-zhi-hui-ling decoction by UHPLC-Q-Orbitrap HRMS.

Pu-zhi-hui-ling decoction (PZHLD) is a traditional Chinese medicine (TCM) formula for the treatment of Alzheimer's disease (AD), but its chemical composition has not been reported. In this study, we aimed to establish a mass spectrometry (MS) analysis method for rapid classification and identification of the chemical constituents in PZHLD. The sample was analysed by ultrahigh-performance liquid chromatography coupled to quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). The chemical constituents of PZHLD were identified based on accurate MS data, fragmentation characteristics of MS/MS, and reference information described in the literature. A total of 123 chemical constituents were identified. In addition, we summarised the fragmentation pathways of the chemical constituents in PZHLD. Our finding might lay the foundation for the further pharmacodynamic study and clinical application of PZHLD.

Investigation of hearing loss in elderly vertigo and dizziness patients in the past 10 years.

Background: Vertigo and hearing loss are both prevalent in the elderly. This study retrospectively analyzed hearing test results from elderly patients experiencing vertigo and dizziness at ENT outpatient over a 10-year period, in order to study the patterns of hearing loss in this patient population. Methods: Nine thousand three hundred eighty four patients over 50 years old underwent retrospective collection and screening of outpatient diagnosis, pure tone audiometry, acoustic immittance measurement (tympanogram) and auditory brainstem response (ABR) test. The patient's audiograms are divided into 7 subtypes according to a set of fixed criteria. Meanwhile, K-Means clustering analysis method was used to classify the audiogram. Results: The Jerger classification of tympanogram in elderly patients with vertigo and dizziness showed the majority falling under type A. The leading audiogram shapes were flat (27.81% in right ear and 26.89% in left ear), high-frequency gently sloping (25.97% in right ear and 27.34% in left ear), and high-frequency steeply sloping (21.60% in right ear and 22.53% in left ear). Meniere's disease (MD; 30.87%), benign recurrent vertigo (BRV; 19.07%), and benign paroxysmal positional vertigo (BPPV; 15.66%) were the most common etiologies in elderly vestibular diseases. We observed statistically significant differences in hearing thresholds among these vestibular diseases (P < 0.001). K-Means clustering analysis suggested that the optimal number of clusters was three, with sample sizes for the three clusters being 2,747, 2,413, and 4,139, respectively. The ANOVA statistical results of each characteristic value showed P < 0.001. Conclusion: The elderly patients often have mild to moderate hearing loss as a concomitant symptom with vertigo. Female patients have better hearing thresholds than males. The dominant audiometric shapes in this patient population were flat, high-frequency gently sloping, and high-frequency steeply sloping according to a set of fixed criteria. This study highlights the need for tailored strategies in managing hearing loss in elderly patients with vertigo and dizziness.

Model-Based Feedback Control for an Automated Micro Liquid Dispensing System Based on Contacting Droplet Generation through Image Sensing.

Over the past few decades, micro liquid dispensing technology has been widely used in biology, chemistry, material and environmental sciences due to its efficacy in processing multiple samples. For practical applications, precise and effective droplet generation is very important. Despite numerous droplet generation methods, the implementation of droplet-on-demand still faces challenges concerning system complexity, precision, cost, and robustness. In this work, a novel on-demand contacting droplet generation method incorporated with model-based feedback control with an image processing unit as a sensor was proposed. By studying droplet identification using image processing techniques, the model of droplet formation was simplified. Then model-based feedback control was implemented using volumes of dispensed samples as sensing signals by tuning related parameters adaptively to resist disturbances. The proposed method was integrated and applied to a homebuilt automated micro liquid dispensing system with droplets ranging from 20 nanoliter to 200 nanoliter. The experimental results demonstrated a high degree of accuracy and precision. Additionally, the proposed system's practical utility was evaluated by analyzing mutations in genes associated with sensorineural hearing loss, verifying its effectiveness.

Multi-Parameter Auto-Tuning Algorithm for Mass Spectrometer Based on Improved Particle Swarm Optimization.

Quadrupole mass spectrometers (QMS) are widely used for clinical diagnosis and chemical analysis. To obtain the best experimental results, mass spectrometers must be calibrated to an ideal setting before use. However, tuning the current QMS is challenging. Traditional tuning techniques possess low automation levels and rely primarily on skilled engineers. Therefore, in this study, we propose an innovative auto-tuning algorithm for QMS based on the improved particle swarm optimization (PSO) algorithm to automatically find the optimal solution of QMS parameters and make the QMS reach the optimal state. The improved PSO algorithm is combined with simulated annealing, multiple inertia weights, dynamic boundaries, and other methods to prevent the traditional PSO algorithm from the issue of a local optimal solution and premature convergence. According to the characteristics of the mass spectrum peaks, a termination function is proposed to simplify the termination conditions of the PSO algorithm and further improve the automation level of the mass spectrometer. The results of auto-calibration testing of resolution and mass axis show that both resolution and mass axis calibration could effectively meet the requirements of mass spectrometry experiments. By the experiment of auto-optimization testing of lens and ion source parameters, these parameters were all in the vicinity of the optimal solution, which achieved the expected performance. Through numerous experiments, the reproducibility of the algorithm was established as meeting the auto-tuning function of the QMS. The proposed method can automatically tune the mass spectrometer from its non-optimal condition to the optimal one, which can effectively reduce the tuning difficulty of QMS.

Machine learning-assisted flexible wearable device for tyrosine detection.

Early diagnosis of pathological markers can significantly shorten the rate of viral transmission, reduce the probability of infection, and improve the cure rate of diseases. Therefore, analytical techniques for identifying pathological markers and environmental toxicants have received considerable attention from researchers worldwide. However, the most popular techniques used in clinical settings involve expensive precision instruments and complex detection processes. Thus, a simpler, more efficient, rapid, and intelligent means of analysis must be urgently developed. Electrochemical biosensors have the advantages of simple processing, low cost, low sample preparation requirements, rapid analysis, easy miniaturization, and integration. Thus, they have become popular in extensive research. Machine learning is widely used in material-assisted synthesis, sensor design, and other fields owing to its powerful data analysis and simulation learning capabilities. In this study, a machine learning-assisted carbon black-graphene oxide conjugate polymer (CB-GO/CP) electrode, in conjunction with a flexible wearable device, is proposed for the smart portable detection of tyrosine (Tyr). Input feature value data are obtained for the artificial neural network (ANN) and support vector machines (SVM) model learning via multiple data collections in artificial urine and by recording the pH and temperature values. The results reveal that a machine-learning model that integrates multiple external factors is more accurate for the prediction of Tyr concentration.

Integrated brain and plasma dual-channel metabolomics to explore the treatment effects of Alpinia oxyphyllaFructus on Alzheimer's disease.

Alpinia oxyphylla Fructus, called Yizhi in Chinese, is the dried fruit of Alpinia oxyphylla Miquel. It has been used in traditional Chinese medicine to treat dementia and memory defects of Alzheimer's disease for many years. However, the underlying mechanism is still unclear. In this study, we used a rat Alzheimer's disease model on intrahippocampal injection of aggregated Aß1-42 to study the effects of Alpinia oxyphylla Fructus. A brain and plasma dual-channel metabolomics approach combined with multivariate statistical analysis was further performed to determine the effects of Alpinia oxyphylla Fructus on Alzheimer's disease animals. As a result, in the Morris water maze test, Alpinia oxyphylla Fructus had a clear ability to ameliorate the impaired learning and memory of Alzheimer's disease rats. 11 differential biomarkers were detected in AD rats' brains. The compounds mainly included amino acids and phospholipids; after Alpinia oxyphylla Fructus administration, 9 regulated biomarkers were detected compared with the AD model group. In the plasma of AD rats, 29 differential biomarkers, primarily amino acids, phospholipids and fatty acids, were identified; After administration, 23 regulated biomarkers were detected. The metabolic pathways of regulated metabolites suggest that Alpinia oxyphylla Fructus ameliorates memory and learning deficits in AD rats principally by regulating amino acid metabolism, lipids metabolism, and energy metabolism. In conclusion, our results confirm and enhance our current understanding of the therapeutic effects of Alpinia oxyphylla Fructus on Alzheimer's disease. Meanwhile, our work provides new insight into the potential intervention mechanism of Alpinia oxyphylla Fructus for Alzheimer's disease treatment.

A Time-Division Multiplexing Multi-Channel Micro-Electrochemical Workstation with Carbon-Based Material Electrodes for Online L-Trosine Detection.

In the background of the rapid development of artificial intelligence, big data, IoT, 5G/6G, and other technologies, electrochemical sensors pose higher requirements for high-throughput detection. In this study, we developed a workstation with up to 10 channels, which supports both parallel signal stimulation and online electrochemical analysis functions. The platform was wired to a highly integrated Bluetooth chip used for wireless data transmission and can be visualized on a smartphone. We used this electrochemical test platform with carbon-graphene oxide/screen-printed carbon electrodes (CB-GO/SPCE) for the online analysis of L-tyrosine (Tyr), and the electrochemical performance and stability of the electrodes were examined by differential pulse voltammetry (DPV). The CB-GO-based screen-printed array electrodes with a multichannel electrochemical platform for Tyr detection showed a low detection limit (20 µM), good interference immunity, and 10-day stability in the range of 20-200 µM. This convenient electrochemical analytical device enables high-throughput detection and has good economic benefits that can contribute to the improvement of the accuracy of electrochemical analysis and the popularization of electrochemical detection methods in a wide range of fields.

Rapid screening of active ingredients and action mechanisms of Ecliptae Herba for treating Alzheimer's disease by UPLC-Q-TOF/MS and "component-target-pathway" network.

Alzheimer's disease (AD) is a common neurodegenerative disease. The drugs widely used in clinic are mainly single-target drugs for symptomatic treatment, which can only alleviate symptoms to a certain extent. Ecliptae Herba (EH) is considered a potential therapeutic drug for AD due to its neuroprotective effects. Although EH has a clear anti-AD effect, the material basis and mechanism remain unclear. Therefore, we adopted an efficient analytical technique, namely ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), combined with "component-target-pathway" network to explore the active components and potential mechanisms of EH in treating AD. Due to the high sensitivity of UPLC-Q-TOF/MS, a total of 50 components were identified in EH. Among them, 20 and 12 compounds were found in plasma and brain samples, respectively. The network pharmacology analysis revealed that apigenin, luteolin, ecliptasaponin A, chlorogenic acid, wedelolactone, and quercetin were the active components, which could affect the serotonergic synapse, calcium and cAMP signaling pathways by regulating related targets such as EGFR, PRKCA, BRAF and ERBB2. This study clarified that EH can exert anti-AD effect through multi-component, multi-target and multi-pathway characteristics. Furthermore, it offers a good foundation for further in-depth research on the anti-AD effects of EH, and provides a valuable approach for the rapid screening of active components and potential mechanisms of other medicinal plants, potentially bringing changes to the discovery and development of novel therapeutics for neurodegenerative disorders.

Efficient Semi-Artificial Photosynthesis of Ethylene by a Self-Assembled InP-Cyanobacterial Biohybrid System.

Biomanufacturing of ethylene is particularly important for modern society. Cyanobacterial cells are able to photosynthesize various valuable chemicals. A promising platform for next-generation biomanufacturing, the semiconductor-cyanobacterial hybrid systems are capable of enhancing the solar-to-chemical conversion efficiency. Herein, the native ethylene-producing capability of a filamentous cyanobacterium Nostoc sphaeroides is confirmed experimentally. The self-assembly characteristic of N. sphaeroides is exploited to facilitate its interaction with InP nanomaterial, and the resulting biohybrid system gave rise to further elevated photosynthetic ethylene production. Based on chlorophyll fluorescence measurement and metabolic analysis, the InP nanomaterial-augmented photosystem I activity and enhanced ethylene production metabolism of biohybrid cells are confirmed, the mechanism underlying the material-cell energy transduction as well as nanomaterial-modulated photosynthetic light and dark reactions are established. This work not only demonstrates the potential application of semiconductor-N. sphaeroides biohybrid system as a good platform for sustainable ethylene production but also provides an important reference for future studies to construct and optimize nano-cell biohybrid systems for efficient solar-driven valuable chemical production.

Pressure-Stabilized High-Entropy (FeCoNiCuRu)S2 Sulfide Anode toward Simultaneously Fast and Durable Lithium/Sodium Ion Storage.

Pressure-stabilized high-entropy sulfide (FeCoNiCuRu)S2 (HES) is proposed as an anode material for fast and long-term stable lithium/sodium storage performance (over 85% retention after 15 000 cycles @10 A g-1 ). Its superior electrochemical performance is strongly related to the increased electrical conductivity and slow diffusion characteristics of entropy-stabilized HES. The reversible conversion reaction mechanism, investigated by ex-situ XRD, XPS, TEM, and NMR, further confirms the stability of the host matrix of HES after the completion of the whole conversion process. A practical demonstration of assembled lithium/sodium capacitors also confirms the high energy/power density and long-term stability (retention of 92% over 15 000 cycles @5 A g-1 ) of this material. The findings point to a feasible high-pressure route to realize new high-entropy materials for optimized energy storage performance.

Quantitative proteomics combined with network pharmacology analysis unveils the biological basis of Schisandrin B in treating diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a major complication of diabetes. Schisandrin B (Sch) is a natural pharmaceutical monomer that was shown to prevent kidney damage caused by diabetes and restore its function. However, there is still a lack of comprehensive and systematic understanding of the mechanism of Sch treatment in DN. OBJECTIVE: We aim to provide a systematic overview of the mechanisms of Sch in multiple pathways to treat DN in rats. METHODS: Streptozocin was used to build a DN rat model, which was further treated with Sch. The possible mechanism of Sch protective effects against DN was predicted using network pharmacology and was verified by quantitative proteomics analysis. RESULTS: High dose Sch treatment significantly downregulated fasting blood glucose, creatinine, blood urea nitrogen, and urinary protein levels and reduced collagen deposition in the glomeruli and tubule-interstitium of DN rats. The activities of superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px) in the kidney of DN rats significantly increased with Sch treatment. In addition, the levels of IL-6, IL-1ß, and TNF-α were significantly reduced in DN rats treated with Sch. 11 proteins that target both Sch and DN were enriched in pathways such as MAPK signaling, PI3K-Akt signaling, renal cell carcinoma, gap junction, endocrine resistance, and TNF signaling. Furthermore, quantitative proteomics showed that Xaf1 was downregulated in the model vs. control group and upregulated in the Sch-treated vs. model group. Five proteins, Crb3, Tspan4, Wdr45, Zfp512, and Tmigd1, were found to be upregulated in the model vs. control group and downregulated in the Sch vs. model group. Three intersected proteins between the network pharmacology prediction and proteomics results, Crb3, Xaf1, and Tspan4, were identified. CONCLUSION: Sch functions by relieving oxidative stress and the inflammatory response by regulating Crb3, Xaf1, and Tspan4 protein expression levels to treat DN disease.

Using a smartphone app in the measurement of posture-related pupil center shift on centration during corneal refractive surgery.

Purpose: Pupil center is an important anchor point in corneal refractive surgery, which may affect by body position. This study investigated the feasibility of using a smartphone application in measurement of posture-related pupil center shifts. Methods: Images of undilated eyes were captured for 25 participants (age: 18-38 years) at a distance of 40 cm in four body positions (seated, supine, right lateral, and left lateral) under controlled lighting conditions. During taking images, a smartphone application was used to guide positioning without head rotation and tilt. From the images, the location of the pupil center and pupil diameter with respect to the limbus boundary were measured. Results: According to the data obtained by the smartphone application, pupil center was located slightly nasal and superior to the limbus center in the seated position, and it shifted more nasally and superiorly (p < 0.001, OD 0.54 ± 0.11 mm, OS 0.57 ± 0.14 mm) in the supine position. When body position switched between left and right lateral positions, the pupil centers of both eyes shifted along the direction of gravity (p < 0.05), and no significant shift occurred along the longitudinal axis. Moreover, pupil constriction was observed when the body position changed from seated to supine position (p < 0.001, OD 0.64 ± 0.57 mm, OS 0.63 ± 0.58 mm). Conclusion: Posture-related pupil center shift may be larger than the error tolerance of centration in corneal refractive surgery, which might be difficult to measure by the existing instruments. An accessible application is necessary for evaluating the shift of pupil center and guiding centration during the surgery.

Electrochemical biosensor based on antibody-modified Au nanoparticles for rapid and sensitive analysis of influenza A virus.

To cope with the easy transmissibility of the avian influenza A virus subtype H1N1, a biosensor was developed for rapid and highly sensitive electrochemical immunoassay. Based on the principle of specific binding between antibody and virus molecules, the active molecule-antibody-adapter structure was formed on the surface of an Au NP substrate electrode; it included a highly specific surface area and good electrochemical activity for selective amplification detection of the H1N1 virus. The electrochemical test results showed that the BSA/H1N1 Ab/Glu/Cys/Au NPs/CP electrode was used for the electrochemical detection of the H1N1 virus with a sensitivity of 92.1 µA (pg/mL)-1 cm2, LOD of 0.25 pg/ml, linear ranges of 0.25-5 pg/mL, and linearity of (R 2 = 0.9846). A convenient H1N1 antibody-based electrochemical electrode for the molecular detection of the H1N1 virus will be of great use in the field of epidemic prevention and raw poultry protection. Supplementary Information: The online version contains supplementary material available at 10.1007/s11581-023-04944-w.

Integrated pharmacokinetics and pharmacometabolomics to reveal the synergistic mechanism of a multicomponent Chinese patent medicine, Mailuo Shutong pills against thromboangiitis obliterans.

BACKGROUND: Mailuo Shutong Pills (MLST) have displayed pharmacological activity against thromboangiitis obliterans (TAO). However, the active ingredients and therapeutic mechanism of MLST against TAO remained to be further clarified. PURPOSE: The aim of this study was to explore the active components of MLST and their synergistic mechanism against TAO by integrating pharmacokinetics (PK) and pharmacometabolomics (PM). METHODS: TAO model rats were established by sodium laurate solution. Firstly, the efficacy of MLST was evaluated by gangrene score, blood flow velocity, and hematoxylin-eosin (H&E) staining. Secondly, PK research was conducted on bioavailable components to characterize their dynamic behaviors under TAO. Thirdly, multiple plasma and urine metabolic biomarkers for sodium laurate-induced TAO rats were found by untargeted metabolomics, and then variations in TAO-altered metabolites following MLST treatment were analyzed utilizing multivariate and bioinformatic analysis. Additionally, metabolic pathway analysis was performed using MetaboAnalyst. Finally, the dynamic link between absorbed MLST-compounds and TAO-associated endogenous metabolites was established by correlation analysis. RESULTS: MLST significantly alleviated gangrene symptoms by improving the infiltration of inflammatory cells and blood supply in TAO rats. Significant differences in metabolic profiles were found in 17 differential metabolites in plasma and 24 in urine between Sham and TAO rats. The 10 bioavailable MLST-compounds, such as chlorogenic acid and paeoniflorin, showed positive or negative correlations with various TAO-altered metabolites related to glutamate metabolism, histidine metabolism, arachidonic acid metabolism and so on. CONCLUSION: This study originally investigated the dynamic interaction between MLST and the biosystem, providing unique insight for disclosing the active components of MLST and their synergistic mechanisms against TAO, which also shed light on new therapeutic targets for TAO and treatment.

Rapid identification of chemical components in vitro and in vivo of Menispermi Rhizoma by integrating UPLC-Q-TOF-MS with data post-processing strategy.

INTRODUCTION: Menispermi Rhizoma (MR), the dried rhizome of Menispermum dauricum DC. (Menispermaceae), has been used to treat sore throat, enteritis, dysentery, and rheumatic arthralgia. Despite extensive research on its pharmacological effects, the chemical components in vitro and in vivo have not been thoroughly studied. OBJECTIVE: To establish an efficient method for rapid classification and identification of alkaloids in MR and its preparations, as well as metabolites in vivo after oral administration of MR. METHODS: Rapid identification of alkaloids and absorbed components of MR was performed using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) coupled with UNIFI software. Moreover, the characteristic fragmentations and neutral losses of different types of alkaloids in MR were summarised to realise the rapid classification of alkaloids. RESULTS: A total of 55 components were unambiguously or tentatively identified in MR. Among them, 37 and 31 components were found in MR capsules and tablets, respectively. Meanwhile, 109 compounds were tentatively identified in rat plasma, urine and faeces, including 55 prototypes and 54 metabolites. Hydrogenation, hydroxylation, methylation, glucuronic acid and sulphate conjugations were the dominating metabolic fates of alkaloids. CONCLUSION: The data post-processing strategy established could greatly enhance the structural identification efficiency. The results obtained might lay the foundation for further interpretation of clinical effects, mechanism of action and quality control of MR.