[CiteSpace knowledge map of research hotspots and frontiers of traditional Chinese medicine intervention in psoriasis in recent ten years].

This study aimed to investigate the development status of traditional Chinese medicine(TCM) intervention in psoriasis in recent ten years, analyze the research hotspots, and summarize the development trends to provide reference materials for scholars in this field. Taking the available literature related to the field of TCM intervention in psoriasis as the research object, the trends, contents, and source publications were statistically analyzed based on bibliometrics. The research cooperation and co-occurrence of keywords in this field were studied by the knowledge map analysis method based on CiteSpace. The total number of Chinese papers was 2 993 and English papers 285. In terms of publication trend, the annual publication of English papers was low but showed an obvious upward trend, while the increase in Chinese papers fluctuated and tended to be flat. In terms of the content of Chinese papers published, TCM ranked first according to the discipline(2 415). In English papers, the number of publications in pharmacology and pharmaceutical science was the highest(87). Literature source analysis showed that the Chinese and English journals with the most publications were China Journal of Traditional Chinese Medicine and Pharmacy and Evidence Based Complementary and Alternative Medicine, respectively. Beijing University of Chinese Medicine published the most dissertations in China(99). The authors with the most publications in Chinese and English were LI Bin(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine) and LU Chuan-jian(Guangdong Hospital of Traditional Chinese Medicine). As revealed by the CiteSpace analysis of the research cooperation network, there were four mature and stable core teams in this field, but the cooperation intensity between different teams was weak. According to the keywords co-occurrence knowledge graph constructed by CiteSpace, the current hot keywords in this field are as follows: psoriasis, blood-heat syndrome, blood-stasis syndrome, fire needle, blood-dryness type, imiquimod, TCM bath, etiology and pathogenesis, cytokines, cupping therapy, etc. In summary, Chinese scholars have conducted active exploration and research in the field of TCM intervention in psoriasis in recent ten years. The overall development trend is good, and the breadth and depth of the research are constantly extending. It is suggested that relevant research should be free from discipline restrictions and strive for interdisciplinary integration.

[Study on mechanism of Rehmanniae Radix Praeparata for treatment of osteoarthritis based on network pharmacology and molecular docking].

The mechanism of Rehmanniae Radix Praeparata against osteoarthritis was investigated based on network pharmacology, molecular docking, and in vitro experiments in the present study. Osteoclast models were established via receptor activator of nuclear factor-κB ligand(RANKL) and macrophage colony-stimulating factor(M-CSF) inducing RAW264.7 cells. Further, the influence of Rehmanniae Radix Praeparata on the activity of tartrate-resistant acid phosphatase(TRAP) was evaluated and the efficacy of Rehmanniae Radix Praeparata in the treatment of osteoarthritis was verified. The active components of Rehmanniae Radix Praeparata were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and literature, and the potential targets of the components were collected from SwissTargetPrediction. Osteoarthritis disease targets were searched in Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), GeneCards, and DisGeNET. The intersection targets of Rehmanniae Radix Praeparata and osteoarthritis were obtained by Venny platform. The protein-protein interaction(PPI) network was constructed by Cytoscape 3.8.2, and key targets were obtained based on topology algorithm. The Database for Annotation, Visualization and Integrated Discovery(DAVID) was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Finally, the mRNA expression of the key targets was determined by RT-qPCR and the binding activity between the components and key targets was validated by molecular docking. The results showed that Rehmanniae Radix Prae-parata inhibited the TRAP activity, thus inhibiting bone resorption by osteoclasts and treating osteoarthritis. By network pharmacology, 14 active components of Rehmanniae Radix Praeparata and 126 intersection targets were obtained. The network pharmacology enrichment results revealed 432 biological processes and 139 signaling pathways. Key targets such as proto-oncogene tyrosine-protein kinase Src(SRC), signal transducer and activator of transcription 3(STAT3) and transcription factor p65(RELA) were obtained according to the degree in topological analysis. SRC was highly expressed in osteoclasts, which accelerated the development of osteoarthritis. Therefore, SRC was selected for subsequent verification, and Rehmanniae Radix Praeparata decreased the gene expression level of SRC. The molecular docking showed that acteoside, isoacteoside, raffinose had good bonding activity with SRC, suggesting that they might be the critical components in treating osteoarthritis. In conclusion, Rehmanniae Radix Praeparata can inhibit bone resorption by osteoclasts and balance the metabolism of articular cartilage and subchondral bone via acting on SRC, thus playing a therapeutic role in osteoarthritis. In addition, Rehmanniae Radix Praeparata may exert overall efficacy on osteoarthritis through other targets such as STAT3 and RELA, and other related pathways such as PI3 K-AKT and IL-17 signaling pathways.

Profiling and identification of chlorogenic acid metabolites in rats by ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer.

1. Chlorogenic acids (CGAs), one kind of major bioactive constituents isolated from Flos Lonicera Japonica, possess many biological activities, such as antibacterial, antioxidant and antiviral activities. In this study, we established an efficient strategy using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of CGAs in rat urine and plasma. 2. The extract from Flos Lonicera Japonica was orally administrated to Sprague-Dawley (SD) rats at a dose of 1000 mg/kg body weight. Then, a combination of various post-acquisition data mining methods, including high-resolution extracted ion chromatogram (HREIC) and multiple mass defect filters (MMDFs) and diagnostic product ions (DPIs), were adopted to characterize the known and unknown CGA metabolites in SD rats. 3. As a result, a total of 68 CGA metabolites were unambiguously or tentatively screened and characterized. These metabolites, including 18 prototype compounds and 50 metabolites, were deduced to be yielded via methylation, hydrogenation, demethylation, dehydration, sulfate conjugation, glucuronide conjugation, glycosylation conjugation and their composite reactions, which mainly occurred to caffeoylquinic acids, dicaffeoylquinic acids, p-coumaroylquinic acids and feruloylquinic acids. 4. In conclusion, this study profiled CGA metabolites, which are useful in understanding the in vivo metabolic fate, effective forms, and pharmacological and toxic actions of CGAs.

Characterization of forsythoside A metabolites in rats by a combination of UHPLC-LTQ-Orbitrap mass spectrometer with multiple data processing techniques.

Forsythoside A (FTA), the main active constituent isolated from Fructus Forsythiae, has various biological functions including anti-oxidant, anti-viral and anti-microbial activities. However, while research on FTA has been mainly focused on the treatment of diseases on a material basis, FTA metabolites in vivo have not been comprehensively evaluated. Here, a rapid and sensitive method using a UHPLC-LTQ-Orbitrap mass spectrometer with multiple data processing techniques including high-resolution extracted ion chromatograms, multiple mass defect filters and diagnostic product ions was developed for the screening and identification of FTA metabolites in rats. As the result, a total of 43 metabolites were identified in biological samples including 42 metabolites in urine, 22 metabolites in plasma and 15 metabolites in feces. These results demonstrated that FTA underwent a series of in vivo metabolic reactions including methylation, dimethylation, sulfation, glucuronidation, diglucuronidation, cysteine conjugation and their composite reactions. The research enhanced our understanding of FTA metabolism and built a foundation for further toxicity and safety studies.

[HUVECs extraction and UHPLC LTQ Orbitrap analysis for screening vascular endothelium protective components in Kudiezi injection].

An effective method has been employed as a tool for screening active components in Kudiezi injection by using cell chromatography and sensitive UHPLC-HR-MSn method. The potential bioactive components in Kudiezi injection could be selectively bound to the HUVECs target cells first. After cell target desensitization and inactivation, the chemical constituents with cell target affinity were identified by LC-MS, so as to screen the possible active components in Kudiezi injection. Based on the accurate mass measurements and the retention time, in total, 9 compounds were tentatively identified and characterized, including 4 sesquiterpene lactones, 3 phenolic acids and 2 flavonoids. HUVECs biospecific extraction coupled with UHPLC-LTQ-Orbitrap analysis could provide a rapid and efficient method for the identification of potential bioactive components in Kudiezi injection, and provide the reference for further research on its effective materials basis.

Identification of Metabolites of 6'-Hydroxy-3,4,5,2',4'-pentamethoxychalcone in Rats by a Combination of Ultra-High-Performance Liquid Chromatography with Linear Ion Trap-Orbitrap Mass Spectrometry Based on Multiple Data Processing Techniques.

In this study, an efficient strategy was established using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of 6'-hydroxy-3,4,5,2',4'-pentamethoxychalcone (PTC) in rat urine and feces. The UHPLC-LTQ-Orbitrap method combines the high trapping capacity and MS(n) scanning function of the linear ion trap along with accurate mass measurements within 5 ppm and a resolving power of up to 30,000 over a wider dynamic range compared to many other mass spectrometers. In order to reduce the potential interferences of endogenous substances, the post-acquisition processing method including high-resolution extracted ion chromatogram (HREIC) and multiple mass defect filters (MMDF) were developed for metabolite detection. As a result, a total of 60 and 35 metabolites were detected in the urine and feces, respectively. The corresponding in vivo reactions such as methylation, hydroxylation, hydrogenation, decarbonylation, demethylation, dehydration, methylation, demethoxylation, sulfate conjugation, glucuronide conjugation, and their composite reactions were all detected in this study. The result on PTC metabolites significantly expanded the understanding of its pharmacological effects, and could be targets for future studies on the important chemical constituents from herbal medicines.

[Influence of different drying methods on steroidal saponins and homoisoflavonoids in Ophiopogon japonicus].

To study the influence of three different drying methods (including 50 ℃-drying, 80 ℃-drying and －70 ℃-freeze-drying methods) on steroidal saponins and homoisoflavonoids in Ophiopogon japonicus,a HPLC-DAD-ELSD-MSn method was investigated to screen and identify the differential components. Through comparing the HPLC chromatograms with that of fresh O. japonicus, 50 ℃-drying medicine was similar with fresh medicine whereas the other two drying methods had great influence on the components of O. japonicus. In this study, 36 differential components were screened, among which 24 constituents(13 homoisoflavonoids and 11 steroidal saponins) were identified via HPLC-LTQ-Orbitrap MS.As a result, it was revealed that different drying methods had significant influences on the components of steroidal saponins and homoisoflavonoids. Among them, 50 ℃-drying method was the most suitable drying approach when the stability of components, cost and practicability were considered.

[Rapid characterization of chemical constituents and rats metabolites of Kudiezi injection by UHPLC-LTQ-Orbitrap].

A rapid and sensitive UHPLC-HR-MSn method was used for the identification of Kudiezi injection and its main metabolites in rat plasma. After the tail intravenous injection of Kudiezi, ACQUITY UHPLC BEH C18 (2.1 mm×100 mm, 1.7 µm) was used, with 0.1% formic acid-acetonitrile solution as the mobile phase for gradient elution. Kudiezi injection and plasma were detected by ESI-LTQ-Orbitrap equipped with an ESI ion source in a negative mode. Based on the accurate mass measurements, the retention time and the mass fragmentation patterns, a total of 53 compounds were tentatively identified and characterized. Furthermore, metabolites in rat plasma after the intravenous administration of Kudiezi injection were also analyzed. A total of 38 compounds were identified, including 27 prototypes and 11 metabolites through metabolic pathways of methylation, glucuronide conjugation, sulfate conjugation and hydrolysis. As a result, UHPLC-LTQ-Orbitrap technique was applied to comprehensively expound Kudiezi injection's chemical components and constituents migrating to rat plasma, and provide scientific basis for further studies on Kudiezi injection's in vivo metabolic process and effective material base.

A rapid new approach for the quality evaluation of the folk medicine Dianbaizhu based on chemometrics.

Dianbaizhu, a folk medicine from Gaultheria leucocarpa BLUME var. yunnanensis (FRANCH.) T. Z. HSU & R. C. FANG (Ericaceae) used as an antirheumatic, has multiple plant origins and officinal parts. A rapid high-performance liquid chromatography with diode array detector (HPLC-DAD) method was established for the simultaneous determination of the characteristic ingredient methyl benzoate-2-O-ß-D-glucopyranosyl(1 → 2) [O-ß-D-xylopyranosyl(1 → 6)]-O-ß-D-glucopyranoside and seven bioactive constituents in eight Gaultheria species. This chromatographic method is precise, accurate, and stable. Kruskal-Wallis analysis, hierarchical cluster analysis, and factor analysis were used to analyze the content of reference compounds in different Gaultheria species and officinal parts. The analyses showed significant differences (p<0.05) in Gaultheria species but few differences (p>0.05) in their medicinal parts. G. leucocarpa var. yunnanensis appeared to the best among the Gaultheria species tested for the treatment of rheumatic diseases. Taken together, the results show that this simultaneous quantification of multiple active constituents using HPLC-DAD combined with chemometrics can be reliably applied to evaluate the quality of Dianbaizhu.

Rapid identification of polymethoxylated flavonoids in traditional Chinese medicines with a practical strategy of stepwise mass defect filtering coupled to diagnostic product ions analysis based on a hybrid LTQ-Orbitrap mass spectrometer.

INTRODUCTION: The methodology of stepwise mass defect filtering (MDF) approach coupled to diagnostic product ions (DPIs) analysis on a hybrid linear trap quadrupole (LTQ)/orbitrap mass spectrometer was the first to be established to screen and identify structural analogues from complex herbal extracts. OBJECTIVE: To develop an analytical methodology that could be adopted to screen and identify structural analogues in traditional Chinese medicines (TCMs) rapidly and accurately. METHODS: Taking polymethoxylated flavonoids (PMFs) in the leaves of Citrus reticulata Blanco as an example, high-resolution mass data were acquired by high-performance liquid chromatography (HPLC) coupled with a LTQ/orbitrap mass spectrometer. The stepwise MDF with multiple mass defect windows or mass windows enabled the original data to be analysed much faster and more accurately by reducing the potential interferences of matrix ions. Additionally, analysis of DPIs could provide a criterion to classify the target constituents detected into certain chemical families. RESULTS: In total, 81 PMFs, including 50 polymethoxyflavones and 31 polymethoxyflavanones or polymethoxychalcones, were screened and identified from the original data and preliminarily identified. CONCLUSION: The analytical methodology developed could be used as a rapid, effective technique to screen and identify compounds from TCM extracts and other organic matter mixtures with compounds that can also be classified into families based on the common carbon skeletons.

[Rapid recognition and identification of chemical constituents in Qinghuo Zhimai tablets by SPE-HPLC-ESI-MS(n)].

OBJECTIVE: To establish a method for analyzing solid phase extraction-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (SPE-HPLC-ESI-MS(n)), in order to recognize and identify the main chemical constituents in Qinghuo Zhimai tablets. METHOD: The possible structures of the compounds were determined according to the structure information of compounds observed from molecular ion peaks and fragment ions in HPLC-ESI-MS(n) negative ion mode and by comparing with literature data or control samples. RESULT: Through the comparative analysis on Qinghuo Zhimai Tablets and components of its formula, 39 chemical constituents were identified, including 7 caffeoylquinic acids, 7 iridoids, 6 diterpenoid lactones, 5 homoisoflavonoids, 13 steroidal saponins and 1 flavone glycoside. CONCLUSION: This study provides a simple and rapid method for identifying chemical components in Qinghuo Zhimai tablets.

[Identification of chemical component from Ixeris sonchifolia and its injection by HPLC-ESI-MS(n)].

A rapid analytical method was developed for the identification of components in Ixeris sonchifolia and its injection by HPLC-ESI-MS(n). The characterization of various components was analyzed according to the retention time of reference standard and mass spectrometry information. A profile of I. sonchifolia and its injection constituents was described and a total of three nucleosides, sixteen phenolic acids, seven flavonoids and twelve sesquiterpene lactones were identified or tentatively characterised. Twelve compounds were accurately identified with reference standards. Eleven of them, guanosine, 1-caffeoylquinic acid, 3-caffeoylquinic acid, 4-caffeoylquinic acid, caffeic anhydride, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3-p-coumaroylquinic acid, 3-feruloylquinic acid, 5-p-coumaroylquinic acid and 4-feruloylquinic acid were reported for the first time in I. sonchifolia and its preparations. The structures of five isomers were deduced by theirs mass information and the fragmentation pattern of known compounds. The developed method was useful for the quality control and evaluation of this herb and its preparations. The HPLC-ESI-MS(n) could be a promising tool for the rapid analysis of components from herbal medicines.

[Rapid identification of 14 bile acids contained in Qingkailing injection by HPLC-ESI-MS/MS].

OBJECTIVE: To investigate ESI-MS/MS fragmentation pattern of bile acids contained in Qingkailing injection, and the rapid identification method. METHOD: HPLC-ESI-MS/MS technology was adopted to investigate ESI-MS/MS fragmentation pattern of five bile acids contained in Qingkailing injection, and rapidly identify bile acids contained in Qingkailing injection from eight different manufacturers. RESULT: 5 bile acids showed similar ESI-MS/MS fragmentation patterns, based on which 14 bile acids were rapidly separated from Qingkailing injection. Among them, 11 were found in injections of all of the manufacturers, and the rest three were found in individual manufacturers. CONCLUSION: HPLC-ESI-MS/MS is used to rapidly identify bile acids from complex material systems, which provides an effective method for interpreting the complex material base of compound traditional Chinese medicine preparations and enhance the quality standards.

[Regularity of changes in chlorogenic acids in Lonicera japonica extracts by HPLC-DAD-ESI-MS/MS].

OBJECTIVE: To analyze chlorogenic acids contained in Lonicera japonica water extracts, and to investigate the regularity of changes in chlorogenic acids during the water extraction process. METHOD: Agilent Zorbax SB-C18 analytical column (4.6 mm x 250 mm, 5 microm) was eluted with 0.1% formic acid (A)-acetonitrile (B) as the mobile phase at a flow rate of 0.5 mL x min(-1). The detection wavelength was 327 nm and the column temperature was 30 degrees C. Negative MS(n) mode was adopted in mass spectrum for ananlyzing the 22 samples of L. japonica water extracts. RESULT: Caffeic acid and six organic acids were accurately identified from the water extracts. During the extraction, the contents of chlorogenic acid and 3,5-dicaffeoylquinic acid became stable or gradually decreased after reaching the highest value. The contents of other components had long been increasing, but with a decreasing rate of change. CONCLUSION: This study provides basis for improving the production process of traditional Chinese medicine preparations containing L. japonica.

Deciphering the chemical profile and pharmacological mechanisms of Baihu-Guizhi decoction using ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry coupled with network pharmacology-based investigation.

BACKGROUND: Baihu-Guizhi decoction (BHGZD) has been extensively used for the treatment of rheumatoid arthritis (RA) with a satisfying therapeutic effect. However, the material basis and the underlying mechanisms of BHGZD against RA have not been fully elucidated. PURPOSE: To investigate the chemical profile and the pharmacological mechanisms of BHGZD against RA. METHODS: The chemical constituents containing in BHGZD were identified using UFLC-Q-TOF-MS/MS system, and the corresponding putative targets were predicted. Then, the differentially expressed genes (DEGs) between adjuvant-induced arthritis (AIA) and normal control groups were identified using microarray analysis. After constructing the interaction network of "RA-related gene-BHGZD putative target", BHGZD candidate targets against RA were screened by topological analysis and further experimentally validated based on AIA rat model. RESULTS: A total of 41 chemical constituents were identified in the water extract of BHGZD, which were predicted to hit 1312 putative targets. Additionally, 26 DEGs between the AIA and normal control groups were defined as "RA-related genes", which were functionally involved into the imbalance of "inflammation-immune" system during RA progression. On the basis of the topological importance in the network of "RA-related gene-BHGZD putative target", 177 BHGZD candidate targets against RA were identified. Among them, TLR4, c-Fos/AP-1, IL2 and TNF had direct interactions with each other and also function as crucial components of toll-like receptor and T cell receptor signaling pathways, which may play important roles in maintaining the balance of "inflammation-immune" system. Experimentally, we verified that BHGZD dose-dependently attenuated the severity, pathological changes, as well as mechanical, cold, and heat hypersensitivities during RA progression based on the AIA rat model. Further western blot analysis demonstrated that BHGZD significantly reduced the protein levels of TLR4, c-Fos/AP-1, IL2 and TNF, which were induced by RA modeling, in the inflamed joints of AIA rats (all p<0.05). CONCLUSION: This study combining the chemical and transcriptomic profilings, target prediction, network calculation and experimental validations identifies the chemical constituents containing in BHGZD and offers the convincing evidence that BHGZD may ameliorate RA partially by restoring the balance of "inflammation-immune" system and subsequently reversing the pathological events during RA progression through regulating the TLR4-c-Fos-IL2-TNF axis.

Rapid screening and identification of sesquiterpene lactones in Kudiezi injection based on high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry.

Sesquiterpene lactones are considered as the major active compounds in Kudiezi injection in virtue of their special structures and activities. Herein, an analytical method was developed for rapid screening and identification of sesquiterpene lactones in Kudiezi injection using high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry (HPLC-LTQ-Orbitrap) in negative ion mode. First, two sesquiterpene lactone reference standards were analyzed to obtain their characteristic ESI-MS/MS fragmentation patterns. Second, based on extracted ion chromatography (EIC) data-mining method and characteristic fragmentation pathways analysis, sesquiterpene lactones in Kudiezi injection were rapidly screened and identified. Finally, an important parameter Clog P was adopted to discriminate the isomers of sesquiterpene lactones. As a result, 50 sesquiterpene lactones were characterized, including 9 sesquiterpene lactone aglycones, 39 sesquiterpene lactone glycosides, and 2 amino acid-sesquiterpene lactone conjugates. Among them, 13 compounds were tentatively identified as new compounds. The results demonstrated that the established method would be a rapid, effective analytical tool for screening and identification of sesquiterpene lactones in the complex system of natural medicines.

Profiling and identification of (-)-epicatechin metabolites in rats using ultra-high performance liquid chromatography coupled with linear trap-Orbitrap mass spectrometer.

(-)-Epicatechin (EC), an optical antipode of (+)-catechin (C), possesses many potential significant health benefits. However, the in vivo metabolic pathway of EC has not been clarified yet. In this study, an efficient strategy based on ultra-high performance liquid chromatography coupled with a linear ion trap-Orbitrap mass spectrometer was developed to profile and characterize EC metabolites in rat urine, faeces, plasma, and various tissues. Meanwhile, post-acquisition data-mining methods including high-resolution extracted ion chromatogram (HREIC), multiple mass defect filters (MMDFs), and diagnostic product ions (DPIs) were utilized to screen and identify EC metabolites from HR-ESI-MS1 to ESI-MSn stage. Finally, a total of 67 metabolites (including parent drug) were tentatively identified based on standard substances, chromatographic retention times, accurate mass measurement, and relevant drug biotransformation knowledge. The results demonstrated that EC underwent multiple in vivo metabolic reactions including methylation, dehydration, hydrogenation, glucosylation, sulfonation, glucuronidation, ring-cleavage, and their composite reactions. Among them, methylation, dehydration, glucosylation, and their composite reactions were observed only occurring on EC when compared with C. Meanwhile, the distribution of these detected metabolites in various tissues including heart, liver, spleen, lung, kidney, and brain were respectively studied. The results demonstrated that liver and kidney were the most important organs for EC and its metabolites elimination. In conclusion, the newly discovered EC metabolites significantly expanded the understanding on its pharmacological effects and built the foundation for further toxicity and safety studies. Copyright © 2017 John Wiley & Sons, Ltd.

An integrated strategy for rapid discovery and identification of the sequential piperine metabolites in rats using ultra high-performance liquid chromatography/high resolution mass spectrometery.

Piperine, one of the major bioactive constituents isolated from natural flavorings and medicinal-culinary herbs, possesses various biological activities. In the present study, an integrated strategy based on ultra high-performance liquid chromatography/high resolution mass spectrometry was established to reveal piperine metabolism in rats. First of all, post-acquisition data-mining methods, including high resolution extracted ion chromatograms (HREICs) and multiple mass defect filtering (MMDF), were used to screen piperine metabolite candidates in a full-scan HRMS1 level. Then, parent ion list-dynamic exclusion coupled with data-dependent data-acquisition method was utilized to acquire MSn datasets. In addition, the established reverse molecular assembly (RMA) approach based on paired diagnostic product ions (pDPIs) coupled with neutral loss fragments (NLFs) was used to ascertain and identify the major-to-trace piperine metabolites efficiently. And then, the calculated ClogP values were utilized to distinguish the positional isomers. As a result, a total of 148 piperine metabolites were detected and characterized tentatively. The results demonstrated that piperine mainly underwent hydrogenation, dehydrogenation, hydroxylation, glucuronide conjugation, sulfate conjugation, ring-cleavage, and their composite reactions. Our results not only provided novel and useful data to better understand the safety, toxicity and efficacy of this potential therapeutic agent, but also indicated that the proposed strategy was reliable for a rapid discovery and identification drug-related constituents in vivo.

Novelty application of multi-omics correlation in the discrimination of sulfur-fumigation and non-sulfur-fumigation Ophiopogonis Radix.

A rapid and sensitive approach to differentiate sulfur-fumigated (SF) Ophiopogonis Radix based on Multi-Omics Correlation Analysis (MOCA) strategy was first established. It was characterized by multiple data-acquisition methods (NIR, HPLC, and UHPLC-HRMS) based metabonomics and multivariate statistical analysis methods. As a result, SF and non-sulfur fumigated (NSF) Ophiopogonis Radix samples were efficaciously discriminated. Moreover, based on the acquired HRMS data, 38 sulfur-containing discriminatory markers were eventually characterized, whose NIR absorption could be in close correlation with the discriminatory NIR wavebands (5000-5200 cm-1) screened by NIR metabonomics coupled with SiPLS and 2D-COS methods. This results were also validated from multiple perspectives, including metabonomics analysis based on the discriminatory markers and the simulation of SF ophiopogonin D and Ophiopogonis Radix sample. In conclusion, our results first revealed the intrinsic mechanism of discriminatory NIR wavebands by means of UHPLC-HRMS analysis. Meanwhile, the established MOCA strategy also provided a promising NIR based differential method for SF Ophiopogonis Radix, which could be exemplary for future researches on rapid discrimination of other SF Chinese herbal medicines.

The genus Liriope: Phytochemistry and pharmacology.

Liriope (Liliaceae) species have been used as folk medicines in Asian countries since ancient times. From Liriope plants (8 species), a total of 132 compounds (except polysaccharides) have been isolated and identified, including steroidal saponins, flavonoids, phenols, and eudesmane sesquiterpenoids. The crude extracts or monomeric compounds from this genus have been shown to exhibit anti-tumor, anti-diabetic, anti-inflammatory, and neuroprotective activities. The present review summarizes the results on phytochemical and biological studies on Liriope plants. The chemotaxonomy of this genus is also discussed.