Rapid identification and determination of chemical components of huai yam based on UPLC-Q-Exactive-MS and fragmentation patterns.

Huai Yam (Dioscoreae Rhizoma) contains many active ingredients such as flavonoids, saponins, and amino acids. In this study, an efficient method for the classification and rapid identification of yam components was established based on UPLC-Q-Exactive-MS and data post-processing techniques. First, the mass spectrometry information including the characteristic fragmentations (CFs) and neutral losses (NLs) of yam reported in the literature were summarised and a database of compounds was established. Then, the mass spectrometry data detected by the yam sample are compared with those described in database for rapid identification of target compounds. Finally, 60 compounds were identified, including 18 flavones, 2 saponins, 10 amino acids, 7 organic acids, 3 carbohydrates, 8 fatty acids and 12 others. A new strategy for identifying target constituents based on CFs and NLs was successfully established, laying the foundation for further research on yam and promoting the development of composition analysis of Traditional Chinese Medicine (TCM).

Rapid classification and identification of chemical components in three different Zanthoxylum species by ultra-high-performance-liquid chromatography quadrupole-orbitrap-mass spectrometry.

Zanthoxylum, as a medicinal and edible herbal medicine, has a long history and complex chemical composition. There are many varieties of Zanthoxylum, and there are differences in composition between varieties. In this study, a rapid classification and identification method for the main components of Zanthoxylum was established using ultra-high-performance-liquid chromatography quadrupole-orbitrap-mass spectrometry. The components of Shandong Zanthoxylum bungeanum, Wudu Zanthoxylum bungeanum, and Zanthoxylum schinifolium were identified by studying the characteristic fragmentations and neutral losses of characteristic components. A total of 48 common components and 24 different components were identified and the fragmentation patterns of the main components, such as flavonoids, alkaloids, and organic acids were summarized. These findings provided a reference for the study of pharmacodynamic substance basis and quality control of different varieties of Zanthoxylum.

Systematic characterization of the chemical constituents in vitro and in vivo of Qianghuo by UPLC-Q-TOF-MS/MS.

The Chinese herb Qianghuo is an antiphlogistic herb with many effects and complex components. In this study, the chemical composition of Qianghuo and its components in rat plasma after oral administration were investigated using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). The extracts, blank plasma, and plasma containing the drug were analyzed by mass spectrometry, and data collected in both positive and negative ion modes were analyzed using Masslynx software, and the structures were confirmed by combining the compound fragment ions and mass spectrometry cleavage pathways. A total of 62 in vitro chemical components were identified, including 27 coumarins, 18 organic acids, 5 amino acids, 5 glycosides, 2 flavonoids, 4 nucleotides, and 1 ester, which were summarized from the obtained compounds in terms of their possible cleavage patterns. Among the identified 31 compounds in rat plasma, 21 were prototypes, mostly coumarins, organic acids, and flavonoids, and 10 were metabolites, which were mainly generated via hydroxylation and methylation pathways. Based on these, this study provides a theoretical foundation for quality control and basic research on Qianghuo medicinal substances.

Analysis of chemical components of Jianwei Xiaoshi Tablets based on UPLC-Q-Orbitrap-MS technology.

As a compound preparation of traditional Chinese medicine, Jianwei Xiaoshi Tablets (JXT) is made from five Chinese herbs: Taizishen (Pseudostellariae Radix), Chenpi (Citri Reticulatae Pericarpium), Shanyao (Dioscoreae Rhizoma), Maiya (Hordei Fructus Germinatus) and Shanzha (Crataegi Fructus). It is mainly used to treat dyspepsia. However, the chemical composition of JXT is complex and unclear. In this study, ultra performance liquid chromatography-quadrupole-orbitrap-mass spectrometry and data post-processing technologies were used to analyse the samples of JXT. Firstly, the mass spectrometric information of the main components of five traditional Chinese herbs in JXT was summarised and a compound database was established. Then, the mass spectrometric data detected by the prepared samples was compared with the database. Finally, 93 chemical components were successfully identified, including 6 amino acids, 34 flavonoids, 18 alkaloids, 15 organic acids, 9 cyclic peptides and 11 other components, and the rapid classification and identification of chemical components of JXT were realised.

Rapid classification and identification of chemical constituents in Leonurus japonicus Houtt based on UPLC-Q-Orbitrap-MS combined with data post-processing techniques.

Leonurus japonicus Houtt (LJH) is a bulk medicinal material commonly used in clinical practice, but its complex constituents have not been completely understood, posing challenges to pharmacology, pharmacokinetic research, and scientific and rational drug use. As a result, it is critical to develop an efficient and accurate method for classifying and identifying the chemical composition of LJH. In this study, ultra-performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry (UPLC-Q-Orbitrap-MS) was successfully established, along with two data post-processing techniques, characteristic fragmentations (CFs) and neutral losses (NLs), to quickly classify and identify the chemical constituents in LJH. As a result, 44 constituents of LJH were identified, including four alkaloids, 20 flavonoids, two phenylpropanoids, 17 organic acids, and one amino acid. The method in this paper enables classification and identification of chemical compositions rapidly, providing a scientific foundation for further research on the effective and toxic substances of LJH.

Rapid identification of chemical compositions of three species of Schisandra chinensis by ultra-high-performance liquid chromatography quadrupole-orbitrap-mass spectrometry.

Schisandra chinensis is a traditional Chinese medicine, which has played an important role in the field of medicine and food. In this study, ultra-high-performance liquid chromatography quadrupole-orbitrap-mass spectrometry was used to rapidly classify and identify the chemical compositions. Note that 32, 28, and 30 kinds of compounds were successfully identified from northern Schisandra chinensis, vinegar-processed Schisandra chinensis, and wine-processed Schisandra chinensis, respectively. The cleavage patterns of various components including lignans, organic acids, flavonoids, and terpenoids were summarized, and the effects of different processing methods on Schisandra chinensis were analyzed through chemical composition. This method realized the rapid classification and identification of raw Schisandra chinensis and two different processed products, and provided references for improving the traditional processing methods, strengthening quality control, and ensuring safe clinical application.

A practical method for rapid discrimination of constituents in Psoraleae Fructus by UPLC-Q-Orbitrap MS.

Psoraleae Fructus (PF) is one of the most frequently used traditional Chinese medicine, which has good efficacy in warming kidney to activate yang, promoting inspiration to relieve asthma and warming spleen to stop diarrhea. However, the chemical composition of PF is complex, which makes it difficult to determine its active and toxic components. In order to rapidly classify and identify the chemical components of the extracts from PF, this research was processed with CNKI, PubMed, and PubChem databases and data post-processing technique basing on ultrahigh performance liquid chromatography quadrupole orbitrap mass spectrometry (UPLC-Q-Orbitrap MS) technique. Finally, 73 chemical components were discriminated, including 44 flavonoids, 18 coumarins, and 11 terpenoids, with the cleavage rules of each chemical component summarized. This study established a UPLC-Q-Orbitrap MS method for the separation and discrimination of the chemical constituents of PF, which can lay a foundation for the further study of its medicinal substances and quality control.

Rapid screening of hepatotoxic components in Uncariae Ramulus Cum Uncis based on "component-target-pathway" network.

As a multi-base source traditional Chinese medicine, the hepatotoxicity of Uncariae Ramulus Cum Uncis (URCU) has been reported repeatedly in recent years. The lack of clarity of toxic components and toxicity mechanisms is a key issue that needs to be addressed. In this article, a "component-target-pathway" network strategy was established to firstly predicting the hepatotoxic components and the toxicity mechanism of URCU. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and data post-processing technology were used to classify and identify the main components in Uncaria rhynchophylla (Miq.) Miq. ex Havil. (UR) and Uncaria sinensis (Oliv.) Havil. (US). Then, the potential hepatotoxic components were screened by network pharmacology and molecular docking. As a result, 40 components and 39 ingredients were identified in UR and US, respectively. Cadambine, rhynchophylline, corynoxeine, isocorynoxeine, strictosamide and mitraphylline were screened as the potential hepatotoxic ingredients contained both in UR and US. The network pharmacology showed that the potential hepatotoxic components could affect the IL-17 signaling pathway by regulating related targets such as MAPK1 and MAPK14, which might lead to the occurrence of liver injury. This study not only provided a reasonable strategy for the rapid screening of hepatotoxic components in URCU, but also supplied reference and guidance for the rational clinical application and scientific supervision of URCU.

A New Strategy for the Rapid Identification and Validation of the Direct Targets of Aconitine-Induced Cardiotoxicity.

BACKGROUND: The interaction of small molecules with direct targets constitutes the molecular initiation events of drug efficacy and toxicity. Aconitine, an active compound of the Aconitum species, has various pharmacological effects but is strongly toxic to the heart. The direct targets of aconitine-induced cardiotoxicity remain unclear. METHODS: We predicted the toxic targets of aconitine based on network pharmacology and followed a novel proteomic approach based on the "drug affinity responsive target stability" technology combined with LC-MS/MS to identify the direct targets of aconitine. The identified targets were analysed from the perspective of multilevel and multidimensional bioinformatics through a network integration method. The binding sites were investigated via molecular docking to explore the toxicity mechanism and predict the direct targets of aconitine. Finally, atomic force microscopy (AFM) imaging was performed to verify the affinity of aconitine to the direct targets. RESULTS: PTGS2, predicted by network pharmacology as a toxic target, encodes cyclooxygenase 2 (COX-2), which is closely related to myocardial injury. Furthermore, cytosolic phospholipase A2 (cPLA2) is the upstream signal protein of PTGS2, and it is a key enzyme in the metabolism of arachidonic acid during an inflammatory response. We determined cPLA2 as a direct target, and AFM imaging verified that aconitine could bind to cPLA2 well; thus, aconitine may cause the expression of PTGS2/COX-2 and release inflammatory factors, thereby promoting myocardial injury and dysfunction. CONCLUSION: We developed a complete set of methods to predict and verify the direct targets of aconitine, and cPLA2 was identified as one. Overall, the novel strategy provides new insights into the discovery of direct targets and the molecular mechanism of toxic components that are found in traditional Chinese medicine.

Preparation and evaluation of Baicalin-loaded cationic solid lipid nanoparticles conjugated with OX26 for improved delivery across the BBB.

PURPOSE: A novel brain targeting drug delivery system based on OX26 antibody conjugation on PEGylated cationic solid lipid nanoparticles (OX26-PEG-CSLN) was prepared. METHODS: The Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody (OX26-PEG-CSLN) were prepared by emulsion evaporation-solidification at low temperature method. The immune-gold labeled OX26-PEG-CSLN was visualized by transmission electron microscopy. The mean diameter and zeta potential of OX26-PEG-CSLN, PEG-CSLN and CSLN were determined using a Zetasizer. The entrapment efficiency of OX26-PEG-CSLN, PEG-CSLN and CSLN was determined by ultrafiltration centrifugation method. And the solid-state characterization of OX26-PEG-CSLN and CSLN were analyzed by X-ray. Pharmacokinetics studies were conducted by in vivo microdialysis in rat cerebrospinal fluid. RESULTS: The results showed that the OX26-PEG-CSLN, PEG-CSLN and CSLN had average diameters of 47.68 ± 1.65, 27.20 ± 1.70 and 33.89 ± 5.74 nm, Zeta potentials of -0.533 ± 0.115 mV, 11.200 ± 0.500 mV and 11.080 ± 1.170 mV and entrapment efficiencies of 83.03 ± 0.01%, 92.90 ± 3.50% and 97.83 ± 0.19%, respectively. In the pharmacokinetics studies, the AUC value of OX26-PEG-CSLN was11.08-fold higher than that of the Baicalin solution (SOL) (p<0.01), and 1.12-fold higher than that of the CSLN (p>0.05); the Cmax value of OX26-PEG-CSLN was 7.88-fold higher than that of SOL (p<0.01) and 1.12-fold (p<0.01) higher than that of the CSLN, respectively. CONCLUSION: These results demonstrated OX26-PEG-CSLN could be a promising carrier to deliver drugs across the BBB for the treatment of brain diseases.

[Effect of three penetration enhancers on corneal permeability of mangiferin in vitro].

OBJECTIVE: To investigate the effects of labrasol, solutol HS 15 and transcutol P on the corneal permeability of mangiferin in vitro. METHOD: The effects of three penetration enhancers on the corneal permeability of mangiferin were investigated in vitro by using isolated rabbit corneas. RESULT: The apparent Papp enhancements were increased 1.80, 3.27, 3.41 and 4.76-folds with Lab at 1.0%, 1.5%, 2.0% and 3.0% (P < 0.01), respectively. The apparent Papp increased 1.98 and 3.07-folds with Sol at 0.2% and 0.4% (P < 0.01), respectively, but reduced with 0.010%-0.03% Trans. CONCLUSION: The Papp value of mangiferin is significantly enhanced by 1.0%-3.0% Lab, 0.2% and 0.4% Sol, however the Papp value of mangiferin is reduced by 0.01%-0.03% Trans.