Qualitative and quantitative analysis of the chemical components in Yuquan capsules by using ultra-performance liquid chromatography-mass spectrometry.

The Yuquan capsules is a commonly used traditional Chinese Patent Medicine used for the treatment of diabetes mellitus. In this study, a high-throughput analytical method for identifying the chemical composition of Yuquan capsules was established for the first time by using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry. The data obtained were subjected to fragment analysis and this was combined with UNIFI processing of natural products. One-hundred sixteen compounds were characterized from Yuquan capsules. Twelve of the bioactive compounds were quantitatively analyzed by ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry. This study was undertaken to obtain a comprehensive chemical profile analysis as well as to evaluate the overall quality of Yuquan capsules. The results will provide a reference for the quality evaluation of different Yuquan preparations. In addition, the data will enable basic pharmacodynamic research into these extensively used capsules.

Quality Markers' Discovery and Quality Evaluation of Jigucao Capsule Using UPLC-MS/MS Method.

Jigucao capsules (JGCC) have the effects of soothing the liver and gallbladder and clearing heat and detoxification. It is a good medicine for treating acute and chronic hepatitis cholecystitis with damp heat of the liver and gallbladder. However, the existing quality standard of JGCC does not have content determination items, which is not conducive to quality control. In this study, serum pharmacochemistry technology and UNIFI data processing software were used to identify the blood prototype components and metabolites under the condition of the obvious drug effects of JGCC, and the referenced literature reports and the results from in vitro analysis of JGCC in the early stage revealed a total of 43 prototype blood components and 33 metabolites in JGCC. Quality markers (Q-markers) were discovered, such as abrine, trigonelline, hypaphorine and isoschaftoside. In addition, ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS) was used to determine the active ingredients in JGCC. The components of quantitative analysis have good correlation in the linear range with R2 ≥ 0.9993. The recovery rate is 93.15%~108.92% and the relative standard deviation (RSD) is less than 9.48%. The established UPLC-MS/MS quantitative analysis method has high sensitivity and accuracy, and can be used for the quality evaluation of JGCC.

Radiation-Triggered Selenium-Engineered Mesoporous Silica Nanocapsules for RNAi Therapy in Radiotherapy-Resistant Glioblastoma.

Radiotherapy-resistant glioblastoma (rrGBM) remains a significant clinical challenge because of high infiltrative growth characterized by activation of antiapoptotic signal transduction. Herein, we describe an efficiently biodegradable selenium-engineered mesoporous silica nanocapsule, initiated by high-energy X-ray irradiation and employed for at-site RNA interference (RNAi) to inhibit rrGBM invasion and achieve maximum therapeutic benefit. Our radiation-triggered RNAi nanocapsule showed high physiological stability, good blood-brain barrier transcytosis, and potent rrGBM accumulation. An intratumoral RNAi nanocapsule permitted low-dose X-ray radiation-triggered dissociation for cofilin-1 knockdown, inhibiting rrGBM infiltration. More importantly, tumor suppression was further amplified by electron-affinity aminoimidazole products converted from metronidazole polymers under X-ray radiation-exacerbated hypoxia, which sensitized cell apoptosis to ionizing radiation by fixing reactive oxygen species-induced DNA lesions. In vivo experiments confirmed that our RNAi nanocapsule reduced tumor growth and invasion, prolonging survival in an orthotopic rrGBM model. Generally, we present a promising radiosensitizer that would effectively improve rrGBM-patient outcomes with low-dose X-ray irradiation.

An ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry identification and characterization of the active constituents from Abrus mollis Hance.

Abrus mollis Hance is a traditional Chinese medicine that is widely used to treat acute and chronic hepatitis, steatosis, and fibrosis. Its therapeutic qualities of it have long been acknowledged, although the active ingredients responsible for its efficacy and the mechanisms of its action are unknown. In this study, the chemical constituents absorbed into the blood from Abrus mollis Hance were assessed by using liquid chromatography-quadrupole-time-of-flight mass spectrometry and the data was analyzed with the UNIFI screening platform. The results obtained were compared to existing chromatographic-mass spectrometry information, including retention times and molecular weights as well as known reference compounds. 41 chemical constituents were found in Abrus mollis Hance, and these included 16 flavonoids, 13 triterpenoids, five organic acids, and two alkaloids. Experimentally it was found that Abrus mollis Hance had a therapeutic benefit when treating α-naphthalene isothiocyanate-induced acute liver injury in rats. In addition, 11 blood prototypical constituents, including six flavonoids, three triterpenoids, and two alkaloids, were found in serum samples following intragastric administration of Abrus mollis Hance extracts to rats. This novel study can be used for the quality control and pharmacodynamic assessment of Abrus mollis Hance in order to assess its efficacy in the therapeutic treatment of patients.

High-Throughput Metabolomics Integrated Network Pharmacology Reveals the Underlying Mechanism of Paeoniae Radix Alba Treating Rheumatoid Arthritis.

OBJECTIVE: The mechanism of action and potential targets of Paeoniae RadixAlba (Baishao, B) in the treatment of adjuvant-induced arthritis (AIA) rats are explained using metabolomics and network pharmacology techniques, and the research evidence for the development of anti-rheumatoid arthritis (RA) drugs is enriched. METHODS: The rats were injected with Freund's complete adjuvant (CFA) to induce arthritis. We then measured the general physical characteristics, examined their X-rays and histopathology to evaluate the pathological condition of the inflammation models, and conducted metabolomics studies on the change in urine metabolism caused by CFA. The lyophilized powder of B at a dose of 2.16 g/kg was orally administered to the rats continuously for 28 days, and the therapeutic effect was evaluated. Network pharmacology prediction shows that B contains the target action of the ingredient, and the simulation of the target molecular docking, in combination with the metabolomics analysis results, shows that B has a potential role in the treatment of AIA rats. RESULTS: B can reduce the paw swelling and pathological changes in rats caused by CFA, reverse the levels of 12 urine biomarkers, and regulate histidine metabolism, phenylalanine metabolism, arginine, proline metabolism, pyrimidine metabolism, etc. The prediction of the active ingredient target in B indicates that it may act as an inflammatory signaling pathway in anti-RA, among them being paeoniflorin, palbinone, beta-sitosterol, kaempferol, and catechin, which are the significant active ingredients. CONCLUSION: The metabolomics results revealed the markers and metabolic mechanisms of urinary metabolic disorders in rats with AIA, demonstrated the efficacy of the therapeutic effect of B, and identified the key ingredients in B, providing theoretical support for the subsequent development and utilization of B.

Potential Mechanisms of Shu Gan Jie Yu Capsule in the Treatment of Mild to Moderate Depression Based on Systemic Pharmacology and Current Evidence.

Background: Shu Gan Jie Yu (SGJY) capsule has a good effect on relieving depressive symptoms in China. However, the mechanism of action is still unclear. Therefore, systemic pharmacology and molecular docking approaches were used to clarify its corresponding antidepressant mechanisms. Methods: Traditional Chinese Medicine Database and Analysis Platform (TCMSP), the Encyclopedia of Traditional Chinese Medicine (ETCM), and Swiss Target Prediction servers were used to screen and predict the bioactive components of the SGJY capsule and their antidepressive targets. Mild to moderate depression (MMD) related genes were obtained from GeneCards and DisGeNET databases. A network of bioactive components-therapeutic targets of the SGJY capsule was established by STRING 11.5 and Cytoscape 3.9.0 software. Gene function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by utilizing Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Active components were taken to dock with the hypothetical proteins by iGEMDOCK and SwissDock, and the docking details were visually displayed by UCSF Chimera software. Then, the related research literature of the SGJY capsule was reviewed, summarized, sorted, and analyzed, including experimental evidence and clinical experience. Results: Seven active components and 45 intersection targets were included in the study. PPI network had genuinely uncovered the potential therapeutic targets, such as AKT1, HSP90AA1, ESR1, EGFR, and PTGS2. KEGG pathway analysis showed that the mechanism of the SGJY capsule on MMD was mainly involved in the PI3K-Akt signaling pathway. Conclusions: In this study, we have successfully predicted the biochemically active constituents, potential therapeutic targets, and comprehensively predicted the related drug-gene interaction of the SGJY capsule for treating MMD and provided a basis for subsequent experiments.

High-Throughput Chinmedomics Strategy Discovers the Quality Markers and Mechanisms of Wutou Decoction Therapeutic for Rheumatoid Arthritis.

Wutou decoction (WTD) is a traditional Chinese medicine prescription for the treatment of rheumatoid arthritis (RA), and this study systematically analyzed the metabolic mechanism and key pharmacodynamic components of WTD in RA rats by combining untargeted metabolomics and serum pharmacochemistry of traditional Chinese medicine to enrich the evidence of WTD quality markers (Q-markers) studies. WTD prevented synovial edema in RA rats and reduced tumor necrosis factor-alpha and interleukin 6 levels in rat serum, according to the results of an enzyme-linked immunosorbent examination and histopathological inspection. In model rats, pattern recognition and multivariate statistical analysis revealed 24 aberrant metabolites that disrupted linoleic acid metabolism, arachidonic acid metabolism, arginine and proline metabolism, etc. However, continued dosing of WTD for 28 days reversed 13 abnormal metabolites, which may be an important therapeutic mechanism from a metabolomic perspective. Importantly, 12 prototypical components and 16 metabolites from WTD were characterized in RA rat serum. The results of Pearson correlation analysis showed that aconitine, L-ephedrine, L-methylephedrine, quercetin, albiflorin, paeoniflorigenone, astragaline A, astragaloside II, glycyrrhetic acid, glycyrrhizic acid, licurazide, and isoliquiritigenin are the key pharmacological components that regulate the metabolism of RA rats, and they are identified as Q-markers. In sum, utilizing metabolomics and serum pharmacochemistry of traditional Chinese medicine, the metabolic mechanisms and Q-markers of WTD therapy in RA rats were revealed, providing a theoretical basis for the quality control investigation of WTD.

[Q-markers of Yuquan Capsules based on serum pharmacochemistry of Chinese medicine].

This study analyzed the quality markers(Q-markers) of Yuquan Capsules(YQC) based on serum pharmacochemistry of Chinese medicine and detected the components and metabolites of YQC absorbed into the blood by UPLC-Q-TOF-MS and UNIFI systems. As a result, 32 components of YQC were detected, including 17 prototype components and 15 metabolized components. Among them, 12 prototype components(ginsenoside Rh_2, genistein, formononetin, puerarin, daidzein, schizandrin A, schizandrin B, schizandrin C, schizandrol A, schizandrol B, gomisin D, and ononin) and 12 metabolized components(ginsenoside Rg_1, ginsenoside Rg_2, ginsenoside Rg_3, ginsenoside Ro, 3'-methoxypuerarin, daidzin, astragaloside Ⅱ, astragaloside Ⅳ, glycyrrhizic acid, liquiritigenin, isoliquiritin, and verbascoside) showed inhibitory effects and pharmacological activities against diabetes, and these 24 blood-entering components against diabetes were identified as Q-markers of YQC.

High throughput metabolomics explores the mechanism of Jigucao capsules in treating Yanghuang syndrome rats using ultra-performance liquid chromatography quadrupole time of flight coupled with mass spectrometry.

To explore the potential mechanism of the Chinese patent medicine Jigucao capsule in treating the serum metabolic profile of rats with Yanghuang syndrome, zingiber officinale Rosc. and ethanol simulates the syndrome background of traditional Chinese medicine and uses α-naphthyl isothiocyanate to induce liver damage in rats to prepare a Yanghuang syndrome model. The histopathological observation and the determination of biochemical indexes evaluate the therapeutic effect of the Jigucao capsule, and the metabolomic method analyzes the mechanism of the Jigucao capsule against Yanghuang syndrome. Jigucao capsule reduces the number of inflammatory cells, inhibits the proliferation of bile duct epithelial cells and hepatocyte necrosis. Compared with Yanghuang syndrome rats, the levels of alanine aminotransferase, alkaline phosphatase, and total bile acid were significantly reduced (P < 0.05). Furthermore, Jigucao capsule significantly reversed the abnormal levels of glucose 1-phosphate, phenylalanyl-cysteine, taurodeoxycholic acid, lysoPC (22:6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z), lysoPC (15:0), lysoPC (P-18:0), 7alpha-hydroxy-3-oxo-4-cholestenoate and 15(S)-hydroxyeicosatrieic acid and regulated part of the lipid metabolism and carbohydrate metabolism, Jigucao capsule has a therapeutic effect on Yanghuang syndrome rats. In short, this study sets for the first time elaborated on the underlying mechanism of Jigucao capsule resistance to Yanghuang syndrome rats from a metabolomics perspective, providing the basic data for the pharmacodynamic studies of the Jigucao capsule.

The Mechanism Study of Common Flavonoids on Antiglioma Based on Network Pharmacology and Molecular Docking.

BACKGROUND: Glioma is the most common primary intracranial tumor in adult patients. Among them, glioblastoma is a highly malignant one with a poor prognosis. Flavonoids are a class of phenolic compounds widely distributed in plants and have many biological functions, such as anti-inflammatory, antioxidant, antiaging, and anticancer. Nowadays, flavonoids have been applied to the therapy of glioma; however, the molecular mechanism underlying the therapeutic effects has not been fully elaborated. This study was carried out to explore the mechanism of selected active flavonoid compounds in treating glioma using network pharmacology and molecular docking approaches. METHODS: Active ingredients and associated targets of flavonoids were acquired by using the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and Swiss TargetPrediction platform. Genes related to glioma were obtained from the GeneCards and DisGeNET databases. The intersection targets between flavonoid targets and glioma-related genes were used to construct protein-protein interaction (PPI) network via the STRING database, and the results were analyzed by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed and displayed by utilizing the Metascape portal and clusterProfiler R package. Molecular docking was carried out by iGEMDOCK and SwissDock, and the results were visually displayed by UCSF Chimera software. RESULTS: Eighty-four active flavonoid compounds and 258 targets overlapped between flavonoid targets and glioma-related genes were achieved. PPI network revealed potential therapeutic targets, such as AKT1, EGFR, VEGFA, MAPK3, and CASP3, based on their node degree. GO and KEGG analyses showed that core targets were mainly enriched in the PI3K-Akt signaling pathway. Molecular docking simulation indicated that potential glioma-related targets-MAPK1 and HSP90AA1 were bounded more firmly with epigallocatechin-3-gallate (EGCG) than with quercetin. CONCLUSIONS: The findings of this study indicated that selected active flavonoid compounds might play therapeutic roles in glioma mainly through the PI3K-Akt signaling pathway. Moreover, EGCG had the potential antiglioma activity by targeting MAPK1 and HSP90AA1.

Rapid characterization of the constituents in Jigucao capsule using ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

Jigucao capsule is a well-known Chinese patent medicine for the treatment of acute and chronic hepatitis and cholecystitis. The chemical components of Jigucao capsule were not clear resulting from the paucity of relevant studies, which hindered the research of the pharmacological mechanism, the comprehensive development, and utilization of Jigucao capsule in clinical studies. By establishing a high-throughput ultra-performance liquid chromatography quadrupole time of flight mass spectrometry in combination with intelligent UNIFI software data processing platform to automatically characterize and identify the chemical profile of Jigucao capsule, 144 compounds were determined rapidly, including 34 terpenoids, 25 flavonoids, 22 steroids, 21 phenylpropanoids, 10 glycosides, six alkaloids, 13 organic acids, and other 13 components. These compounds may be the active components of Jigucao capsule. In this study, a rapid and robust method for comprehensively analyzing the chemical composition of Jigucao capsule was described and established for the first time. The results will provide a reference for the quality control of Jigucao capsule and the establishment of a higher quality standard, as well as for the pharmacodynamic material basis research.

Applications and potential mechanisms of herbal medicines for rheumatoid arthritis treatment: a systematic review.

In this review, we systematically discuss the role of traditional Chinese medicine (TCM) in rheumatoid arthritis (RA) disease treatment. TCM classifies the subtypes of RA through its own theoretical method, which is beneficial for more accurate diagnosis and treatment with Chinese herbal medicines (CHMs) that are more suitable for different syndromes. TCM mainly uses a flexible combination of CHMs to play an important role in RA treatment. The main components of these extracts can be subdivided into alkaloids, flavonoids, triterpenes, saponins and other compounds. Using a platform of transgenic and induced arthritis models, we explore the potential mechanisms of TCM against RA with the help of omics analysis techniques and methods. These mechanisms are mainly CHM and its extracts can inhibit RA patients and experimental animal models, including synovitis, vascular proliferation and bone injury; this involves many biological signal exchange targets and pathways. In conclusion, the role of TCM in RA treatment mainly involves reducing the expression and secretion of pro-inflammatory factors, thus decreasing the degree of abnormal immune response.