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Hypericum perforatum L. (HPL), also known as St. John's wort, is one of the extensively researched domestically and internationally as a medicinal plant. In this study, non-targeted metabolomics combined with machine learning methods were used to identify reasonable quality indicators for the holistic quality control of HPL. First, the high-resolution MS data from different samples of HPL were collected, and visualized the chemical compounds through the MS molecular network. A total of 122 compounds were identified. Then, the orthogonal partial least squares-discriminant analysis (OPLS-DA) model was established for comparing the differences in metabolite expression between flower, leaf, and branches. A total of 46 differential metabolites were screened out. Subsequently, analyzing the pharmacological activities of these differential metabolites based on protein-protein interaction (PPI) network. A total of 25 compounds associated with 473 gene targets were retrieved. Among them, 13 highly active compounds were selected as potential quality markers, and five compounds were ultimately selected as quality control markers for HPL. Finally, three different classifiers (support vector machine (SVM), random forest (RF), and K-nearest neighbor (KNN)) were used to validate whether the selected quality control markers are qualified. When the feature count is set to 122 and 46, the RF model demonstrates optimal performance. As the number of variables decreases, the performance of the RF model degrades. The KNN model and the SVM model also exhibit a decrease in performance but still manage to satisfy the intended requirements. The strategy can be applied to the quality control of HPL and can provide a reference for the quality control of other herbal medicines. [Display omitted] • A custom-built database was built to visualized the compounds present in HPL. • An OPLS-DA model was established to selected differential metabolites. • The PPI network was established to selected the active compounds. • Three classifiers were used to assess the qualification of quality markers. [ABSTRACT FROM AUTHOR]

• Parasitic Loranthaceae species do not contain cardiac glycosides. • Cardiac glycosides were effectively detected in Nerium indicum. • Cardiac glycosides were detected in Loranthaceae parasitizing N. indicum. • N. indicum host plants export cardiac glycosides to its parasitic plants. • Cardiac glycosides detected in N. indicum were all type I or II glycosides. To evaluate the effect of the host plant on the quality of Loranthaceae species as medicinal raw material, ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to identify cardiac glycosides in Nerium indicum and its parasitic plant species Taxillus chinensis and Scurrula parasitica. Samples were collected from N. indicum and these parasites, while Morus alba and its parasite T. chinensis and Osmanthus fragrans and its parasite S. parasitica were used as controls. Based on mass spectrometry data and elemental composition analysis of positive and negative ion modes, in combination with standard cardiac glycosides and relevant literature, cardiac glycosides in N. indicum and its parasites T. chinensis and S. parasitica were identified, and their correlations were analyzed. A total of 29 cardiac glycosides were identified, among which 28 were found in N. indicum parasitized by T. chinensis ; 25 cardiac glycosides were identified in the same host under attack by S. parasitica ; five cardiac glycosides were identified in both T. chinensis and S. parasitica, which grew parasitically on N. indicum , whereas no cardiac glycosides were identified in M. alba parasitized by T. chinensis , or in O. fragrans parasitized by S. parasitica. We conclude that UPLC-Q-TOF-MS/MS technology can identify cardiac glycosides in N. indicum and parasites T. chinensis and S. parasitica rapidly, accurately, and thoroughly. N. indicum will transfer its own cardiac glycosides to its parasites through the special host–parasite interaction. Our results provide a reference basis for evaluating the influence of the host plant on the quality of medicinal compounds obtained from Loranthaceae species. [ABSTRACT FROM AUTHOR]

Shen-Wu-Yi-Shen tablet (SWYST), a well-known traditional Chinese medicine prescription (TCMP), has been effectively used for treating chronic kidney disease (CKD) in clinically. However, an in-depth study of in vivo metabolism of SWYST is lacking. In this study, a targeted and non-targeted strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) was developed to screen and characterize SWYST-related xenobiotics in rats. Based on the in-house library, a chemical database of SWYST including 215 constituents was constructed through "find by formula" and further verified by characteristic fragmentations or the literatures. Then the constructed chemical database was applied for the targeted screening of prototypes. As for metabolites, the non-targeted screening was achieved combined the peak picking using the function "find by auto-MS/MS" and peak filtration of the prototypes and endogenous components, while the targeted screening was performed using Metabolite ID according to the possible metabolic reactions. Furthermore, the potential metabolites were preliminarily identified by comparison of the parent compounds or references to the literatures. As a result, 201 exogenous components (87 prototypes and 121 metabolites) were characterized in rats after administration of SWYST, including 55 (17 prototypes and 38 metabolites) in plasma, 151 (52 prototypes and 99 metabolites) in urine, and 121 (74 prototypes and 47 metabolites) in feces. Finally, their possible metabolic pathways were summarized, and the metabolic reactions mainly involved phase I reactions (hydroxylation, deoxygenation, hydrogenation, methylation, oxidation, hydrolysis and esterification) and phase II reactions (glucuronidation and sulfation). The findings of this research reveal the potential active ingredients of SWYST, providing an important material basis for the pharmacokinetics and pharmacodynamics of SWYST. • In vivo metabolism of SWYST was first investigated combined with a targeted and non-targeted strategy. • Fragmentation pathways of the stilbene-related metabolites were systematically elucidated. • Sterone-related metabolites were reported and their possible metabolic pathways were summarized. [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19) caused by SARS-COV-2 infection has been widely prevalent in many countries and has become a common challenge facing mankind. Traditional Chinese medicine (TCM) has played a prominent role in this pandemic, and especially TCM with the function of "heat-clearing and detoxifying" has shown an excellent role in anti-virus. Fufang Shuanghua oral liquid (FFSH) has been used to treat the corresponding symptoms of influenza such as fever, nasal congestion, runny nose, sore throat, and upper respiratory tract infections in clinic, which are typical symptoms of COVID-19. The content of chlorogenic acid, andrographolide and dehydrated andrographolide as the quality control components of FFSH is not less than 1.0 mg/mL, 60 μg/mL and 60 μg/mL respectively. In this study, UPLC-Q-TOF-MS/MS was employed to describe the chemical profile of FFSH. Virtual screening and fluorescence resonance energy transfer (FRET) were used to screen the effective components of FFSH acting on SARS-CoV-2 main protease (Mpro). As a result, 214 compounds in FFSH were identified or preliminarily characterized by UPLC-Q-TOF-MS/MS, and 61 active ingredients with potential inhibitory effects on Mpro were selected through receptor-based and ligand-based virtual screening. In particular, quercetin, forsythoside A, and linoleic acid showed a good inhibitory effect on Mpro in FRET evaluation with IC50 values of 26.15 μM, 22.26 μM and 47.09 μM respectively, and had a strong binding affinity with the receptor Mpro (6LU7) in molecular docking. CYS145 and HIS41 were the main amino acid residues affected by small molecules in the protein binding domain. In brief, we characterized, for the first time, 214 chemical components in FFSH, and three of them, including quercetin, forsythoside A and linoleic acid, were screened out to exert beneficial anti-COVID-19 effects through CYS145 and HIS41 sites, which may provide a new research strategy for TCM to develop new therapeutic drugs against COVID-19. [Display omitted] • The first time, 214 components were identified in Fufang Shuanghua by UPLC-QTOF-MS. • 64 components were selected by receptor- and ligand-based virtual screening. • Quercetin, forsythoside A and linoleic acid were anti-COVID-19 by CYS145 and HIS41. [ABSTRACT FROM AUTHOR]

Bicyclol (BIC) has been widely used to treat drug-induced liver injury (DILI), however, it still has the problems of low solubility and bioavailability. Besides, the metabolic characteristics of BIC remain unclear. In the current study, we identified the metabolite of BIC in rat plasma, urine and feces, and evaluated the efficacy and safety of these metabolites. Based on the fragmentation behavior, we totally identified 11 metabolites and 7 metabolites in plasma, 8 metabolites in urine and 8 metabolites in feces. Notably, M1-M3, M6, M7, M10 and M11 were identified for the first time. M7 was the most abundant metabolite in the rat plasma. The metabolic pathways mainly involved demethylation, dealkylation, hydrolysis, methylation, oxidation and glucuronidation. In addition, the efficacy and safety of BIC's metabolites were evaluated by network pharmacology and molecular docking combined with toxicity prediction. The analysis of network pharmacology indicated that BIC's metabolites against DILI through the MAPK signaling pathway and Hepatitis B pathway. The molecular docking results showed that the binding energy of 5 compounds that docked with "7nuw" and 10 compounds that docked with "4tjz" was lower than BIC. 11 compounds possessed higher solubility and lower toxicity than BIC in prediction. Thus, the identification and evaluation of BIC's metabolites contributed to a better understanding of pharmacological mechanism of BIC and the high-value metabolites of high efficacy, safety and solubility provided a basis for drug development. • The metabolic profiles of BIC were identified in rat plasma, urine and feces. • Totally 7 BIC's metabolites were identified for the first time. • BIC's metabolites treated DILI through MAPK and Hepatitis B pathway. • High-value metabolites provided a basis for drug development. [ABSTRACT FROM AUTHOR]

Abstract: SiJunZiTang (SJZT), a classic Traditional Chinese Formula (TCMF) consisting of four herbs, Radix Ginseng, Atractylodes macrocephala, Poria cocos and Glycyrrhiza uralensis, has been demonstrated to show protective effects on intestine and stomach injure. The chromatographic quality control is needed. UPLC–Q-TOF-MS is a rapid and efficient technique for analysis of complex sample in combination with UPLC and tandem mass spectrometry (MS/MS). In this paper, UPLC–MS fingerprinting of SJZT was developed. As a result, 66 compounds including ginsenosides, flavonoids, triterpenoid and coumarins were detected, 58 of them were tentatively identified. The major constituents of SJZT were ginsenosides and flavonoids that coming from Radix Ginseng and Glycyrrhiza uralensis. [Copyright &y& Elsevier]

Abstract: An UPLC–Q-TOF-MS/MS based chemical profiling method was developed to evaluate decocting-induced chemical transformations in Du–Shen–Tang, the decoction of the root of Panax ginseng. Under the optimized UPLC and Q-TOF-MS/MS conditions, over 50 peaks were separated and detected in Du–Shen–Tang within 18min. The components were identified by comparing the mass spectra and retention time with that of reference compounds, and/or tentatively assigned by elucidating low energy CID fragment ions as well as matching empirical molecular formula with that of the published known compounds. Totally 45 major ginsenosides were identified in Du–Shen–Tang, 21 of which were determined to be newly generated during the decoction of ginseng. The mechanisms involved were further deduced to be hydrolysis, dehydration, decarboxylation and addition reactions of the original ginsenosides in white ginseng through analyzing mimic decoctions of 13 pure reference ginsenosides. Significant difference in chemical profiles between decoctions of two batches of white ginseng suggested that storage duration or other factors significantly influenced the quality consistency of not only the crude drug but also the decoction (Du–Shen–Tang) of white ginseng. [ABSTRACT FROM AUTHOR]