Integrated pharmacokinetic-pharmacodynamic modeling and metabolomic research on polyphenol-rich fraction of Thymus quinquecostatus Celak. Alleviating cerebral ischemia-reperfusion injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Thymus quinquecostatus Celak., a member of thymus genus in Lamiaceae family, has been used as a folk medicine for relieving exterior syndrome and alleviating pain in China. The polyphenol-rich fraction (PRF) derived from Thymus quinquecostatus Celak. had been validated that it can protect cerebral ischemia-reperfusion injury (CIRI) by activating Keap1/Nrf2/HO-1 signaling pathway. AIM OF THIS STUDY: To explore effective components and their pharmacokinetic and pharmacodynamic characteristics as well as possible mechanisms of PRF in treating CIRI. MATERIALS AND METHODS: Normal treated group (NTG) and tMCAO model treated group (MTG) rats were administrated PRF intragastrically. The prototype components and metabolites of PRF in plasma and brain were analyzed by the UPLC-Q-Exactive Orbitrap MSn method. Subsequently, the pharmacokinetics properties of indicative components were performed based on HPLC-QQQ-MS/MS. SOD and LDH activities were determined to study the pharmacodynamic (PD) properties of PRF. The PK-PD relationship of PRF was constructed. In addition, the effect of PRF on endogenous metabolites in plasma and brain was investigated using metabolomic method. RESULTS: Salvianic acid A, caffeic acid, rosmarinic acid, scutellarin, and apigenin-7-O-glucuronide were selected as indicative components based on metabolic analysis. The non-compartmental parameters were calculated for indicative components in plasma and brain of NTG and MTG rats. Furthermore, single-component and multi-component PK-PD modeling involved Emax, Imax PD models for effect indexes were fitted as well as ANN models were established, which indicated that these components can work together to regulate SOD and LDH activities in plasma and SOD activity in brain tissue to improve CIRI. Additionally, PRF may ameliorate CIRI by regulating the disorder of endogenous metabolites in lipid metabolism, amino acid metabolism, and purine metabolism pathways in vivo, among which lipid metabolism and purine metabolism are closely related to oxidative stress. CONCLUSION: The PK-PD properties of effect substances and mechanisms of PRF anti-CIRI were further elaborated. The findings provide a convincing foundation for the application of T. quinquecostatus Celak. in the maintenance of human health disorders.

Bao Yuan decoction alleviates fatigue by restraining inflammation and oxidative stress via the AMPK/CRY2/PER1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Baoyuan Decoction (BYD) was initially recorded in the classic of "Bo Ai Xin Jian" in the Ming dynasty. It is traditionally used for treating weakness and cowardice, and deficiency of vital energy. In researches related to anti-fatigue effects, the reciprocal regulation of AMPK and circadian clocks likely plays an important role in anti-fatigue mechanism, while it has not yet been revealed. Therefore, we elucidated the anti-fatigue mechanism of BYD through AMPK/CRY2/PER1 pathway. AIM OF THE STUDY: To investigate the effect and mechanism of BYD in reducing fatigue, using pharmacodynamics, network pharmacology and transcriptomics through the AMPK/CRY2/PER1 signaling pathway. MATERIALS AND METHODS: Firstly, the chemical constituents of BYD were qualitatively identified by UHPLC-Q-Exactive Orbitrap/MS, establishing a comprehensive strategy with an in-house library, Xcalibur software and Pubchem combined. Secondly, a Na2SO3-induced fatigue model and 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress model were developed to evaluate the anti-fatigue and anti-oxidant activities of BYD using AB zebrafish. The anti-inflammatory activity of BYD was evaluated using CuSO4-induced and tail cutting-induced Tg (lyz: dsRed) transgenic zebrafish inflammation models. Then, target screening was performed by Swiss ADME, GeneCards, OMIM and DrugBank databases, the network was constructed using Cytoscape 3.9.0. Transcriptome and network pharmacology technology were used to investigate the related signaling pathways and potential mechanisms after treatment with BYD, which were verified by real-time quantitative PCR (RT-qPCR). RESULTS: In total, 114 compounds from the water extract of BYD were identified as major compounds. Na2SO3-induced fatigue model and AAPH-induced oxidative stress model indicated that BYD has significant anti-fatigue and antioxidant effects. Meanwhile, BYD showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. The KEGG result of network pharmacology showed that the anti-fatigue function of BYD was mainly effected through AMPK signaling pathway. Besides, transcriptome analysis indicated that the circadian rhythm, AMPK and IL-17 signaling pathways were recommended as the main pathways related to the anti-fatigue effect of BYD. The RT-qPCR results showed that compared with a model control group, the treatment of BYD significantly elevated the expression mRNA of AMPK, CRY2 and PER1. CONCLUSION: Herein, we identified 114 chemical constituents of BYD, performed zebrafish activity validation, while demonstrated that BYD can relieve fatigue by AMPK/CRY2/PER1 signaling pathway through network pharmacology and transcriptome.

Relationship between gut microbiota and rheumatoid arthritis: A bibliometric analysis.

Introduction: Rheumatoid arthritis (RA) is a multifactorial autoimmune disease. Recently, growing evidence demonstrates that gut microbiota (GM) plays an important role in RA. But so far, no bibliometric studies pertaining to GM in RA have ever been published. This study attempts to depict the knowledge framework in this field from a holistic and systematic perspective based on the bibliometric analysis. Methods: Literature related to the involvement of GM in RA was searched and picked from the Web of Science Core Collection (WOSCC) database. The annual output, cooperation, hotspots, research status and development trend of this field were analyzed by bibliometric software (VOSviewer and Bibliometricx). Results: 255 original research articles and 204 reviews were included in the analysis. The articles in this field that can be retrieved in WOSCC were first published in 2004 and increased year by year since then. 2013 is a growth explosion point. China and the United States are the countries with the most contributions, and Harvard University is the affiliation with the most output. Frontiers in Immunology (total citations = 603) is the journal with the most publications and the fastest growth rate. eLife is the journal with the most citations (total citations = 1248). Scher, Jose U. and Taneja, Veena are the most productive and cited authors. The research in this field is mainly distributed in the evidence, mechanism and practical application of GM participating in RA through the analysis of keywords and documents. There is sufficient evidence to prove the close relationship between GM and RA, which lays the foundation for this field. This extended two colorful and tender branches of mechanism research and application exploration, which have made some achievements but still have broad exploration space. Recently, the keywords "metabolites", "metabolomics", "acid", "b cells", "balance", "treg cells", "probiotic supplementation" appeared most frequently, which tells us that research on the mechanism of GM participating in RA and exploration of its application are the hotspots in recent years. Discussion: Taken together, these results provide a data-based and objective introduction to the GM participating in RA, giving readers a valuable reference to help guide future research.

Curcumae Rhizoma - combined with Sparganii Rhizoma in the treatment of liver cancer: Chemical analysis using UPLC-LTQ-Orbitrap MSn, network analysis, and experimental assessment.

Objective: Curcumae Rhizoma-Sparganii Rhizoma (CR-SR) is a traditional botanical drug pair that can promote blood circulation, remove blood stasis, and treat tumors in clinics. The aim of the present study was to investigate the therapeutic material basis and potential mechanisms of CR-SR, CR, and SR for the treatment of liver cancer. Method: The chemical profile analyses of CR-SR, CR, and SR were performed by molecular networking and UPLC-LTQ-Orbitrap MSn. The anti-liver cancer activities of CR-SR, CR, and SR were assessed by using a zebrafish xenograft model in vivo for the first time and detected by the HepG2 cell model in vitro. Combining the network analysis and molecular docking, real-time quantitative polymerase chain reaction (RT-qPCR) experiments were undertaken to further explore the mechanisms of CR-SR, CR, and SR for the treatment of liver cancer. Results: In total, 65 components were identified in CR-SR, CR, and SR. Based on the clusters of molecular networking, a total of 12 novel diarylheptanoids were identified from CR-SR and CR. By combining our results with information from the literature, 32 sesquiterpenoids and 21 cyclic dipeptides were identified from CR-SR, CR, and SR. The anti-liver cancer activities were observed in both the drug pair and the single botanical drugs in vitro and in vivo, and the order of activity was CR-SR > CR > SR. They could downregulate the expression of proto-oncogene tyrosine-protein kinase Src (SRC), epidermal growth factor receptor (EGFR), estrogen receptor-α (ESR1), prostaglandin endoperoxide synthase 2 (PTGS2), and amyloid precursor protein (APP). Conclusion: Taken together, the present study provided an experimental basis for the therapeutic material basis and potential molecular mechanisms of CR-SR, CR, and SR. This study provided a novel insight for objective clinical treatment of liver cancer.

A Systematic Review on Polysaccharides from Dendrobium Genus: Recent Advances in the Preparation, Structural Characterization, Bioactive Molecular Mechanisms, and Applications.

Dendrobium polysaccharides (DPSs) have aroused people's increasing attention in recent years as a result of their outstanding edible and medicinal values and non-toxic property. This review systematically summarized recent progress in the different preparation techniques, structural characteristics, modification, various pharmacological activities and molecular mechanisms, structure-activity relationships, and current industrial applications in the medicinal, food, and cosmetics fields of DPSs. Additionally, some recommendations for future investigations were provided. A variety of methods were applied for the extraction and purification of DPSs. They possessed primary structures (e.g., glucomannan, rhamnogalacturonan I type pectin, heteroxylan, and galactoglucan) and conformational structures (e.g., random coil, rod, globular, and a slight triple-helical). And different molecular weights, monosaccharide compositions, linkage types, and modifications could largely affect DPSs' bioactivities (e.g., immunomodulatory, anti-diabetic, hepatoprotective, gastrointestinal protective, antitumor, anti-inflammatory, and anti-oxidant activities). It was worth mentioning that DPSs were significant pharmaceutical remedies and therapeutic supplements especially due to their strong immunity enhancement abilities. We hope that this review will lay a solid foundation for further development and applications of Dendrobium polysaccharides.

Multi-omics integration reveals the hepatoprotective mechanisms of ursolic acid intake against chronic alcohol consumption.

PURPOSE: Alcoholic liver disease (ALD) is a major health issue globally. In addition to pharmacotherapy, dietary support is also regarded as reliable strategy for ALD management. As a widely distributed natural constituent within edible plants, the present study aims to investigate the hepatoprotective effects of ursolic acid (UA) against ALD and also to deepen insights into the underlying targets and mechanisms comprehensively. METHODS: The hepatoprotective activity of UA against chronic alcohol-induced liver injury was investigated on Lieber-DeCarli liquid diet-based mouse model. In-depth RNA-seq transcriptomics and TMT-based proteomics analyses were conducted in parallel. Data integration as well as bioinformatics analysis were also performed to unravel the targets and mechanisms associated with the hepatoprotective activity of UA intake against alcoholic liver injury comprehensively. RESULTS: The serum biomarkers and pathological characteristics indicated the hepatoprotective effects of UA intake on alcoholic liver injury. 567 target genes and 377 target proteins related to the hepatoprotective activity of UA were identified in transcriptomics and proteomics analysis respectively, most of which were associated with function of cellular process, cell part and binding. After data integration, 56 co-regulated targets, including ADH4, CYP450 enzymes, NQO1, apolipoproteins, glutathione-S-transferase, etc. which were consistently modulated on both mRNA and protein levels were identified. These co-regulated targets were found to be correlated with 70 KEGG pathways led by carcinogenesis, retinol metabolism and CYP450 metabolism pathways. CONCLUSION: UA intake ameliorated chronic alcohol-induced liver injury. Given the role of the co-regulated targets in ALD and the bioinformatics analysis results, CYP450-, glutathione and redox homeostasis-dependent antioxidation, promotion of lipid transport, and restoration of ethanol metabolic capacity are the potentially underlying mechanisms. This information will further deepen our insights into the hepatoprotective effects of UA-rich edible plants, and provide us valuable instruction for ALD management.

Gaultheria leucocarpa var. yunnanensis for Treating Rheumatoid Arthritis-An Assessment Combining Machine Learning-Guided ADME Properties Prediction, Network Pharmacology, and Pharmacological Assessment.

Background: Dianbaizhu (Gaultheria leucocarpa var. yunnanensis), a traditional Chinese/ethnic medicine (TC/EM), has been used to treat rheumatoid arthritis (RA) for a long time. The anti-rheumatic arthritis fraction (ARF) of G. yunnanensis has significant anti-inflammatory and analgesic activities and is mainly composed of methyl salicylate glycosides, flavonoids, organic acids, and others. The effective ingredients and rudimentary mechanism of ARF remedying RA have not been elucidated to date. Purpose: The aim of the present study is to give an insight into the effective components and mechanisms of Dianbaizhu in ameliorating RA, based on the estimation of the absorption, distribution, metabolism, and excretion (ADME) properties, analysis of network pharmacology, and in vivo and in vitro validations. Study design and methods: The IL-1ß-induced human fibroblast-like synoviocytes of RA (HFLS-RA) model and adjuvant-induced arthritis in the rat model were adopted to assess the anti-RA effect of ARF. The components in ARF were identified by using UHPLC-LTQ-Orbitrap-MSn. The quantitative structure-activity relationship (QSAR) models were developed by using five machine learning algorithms, alone or in combination with genetic algorithms for predicting the ADME properties of ARF. The molecular networks and pathways presumably referring to the therapy of ARF on RA were yielded by using common databases and visible software, and the experimental validations of the key targets conducted in vitro. Results: ARF effectively relieved RA in vivo and in vitro. The five optimized QSAR models that were developed showed robustness and predictive ability. The characterized 48 components in ARF had good biological potency. Four key signaling pathways were obtained, which were related to both cytokine signaling and cell immune response. ARF suppressed IL-1ß-induced expression of EGFR, MMP 9, IL2, MAPK14, and KDR in the HFLS-RA . Conclusions: ARF has good druggability and high exploitation potential. Methyl salicylate glycosides and flavonoids play essential roles in attuning RA. ARF may partially attenuate RA by regulating the expression of multi-targets in the inflammation-immune system. These provide valuable information to rationalize ARF and other TC/EMs in the treatment of RA.

Gut dysbiosis correction contributes to the hepatoprotective effects of Thymus quinquecostatus Celak extract against alcohol through the gut-liver axis.

Alcoholic liver disease (ALD) is a major health issue globally due to the consumption of alcoholic beverages. Thymus quinquecostatus Celak is a food additive and an edible herb that is widely used in Asia and possesses hepatoprotective activity, but the underlying mechanisms behind this protective activity are not completely understood. The purpose of this study was to investigate the hepatoprotective effects of Thymus quinquecostatus Celak extract (TQE) against ALD as well as the underlying mechanism based on gut microbiota and the gut-liver axis. TQE supplementation markedly alleviated chronic alcohol-induced liver injury in C57 mice. TQE also ameliorated gut barrier dysfunction induced by alcohol. Consequently, the activation of the lipopolysaccharide (LPS) translocation-mediated TLR4 pathway and the subsequent inflammatory response and ROS overproduction in the liver were suppressed. Meanwhile, alcohol-induced gut microbiota dysbiosis was also corrected by TQE. To further investigate the contribution of gut dysbiosis correction to the beneficial effects of TQE on ALD, a fecal microbiota transplantation study was conducted. TQE-manipulated gut microbiota transplantation markedly counteracted the alcohol-induced gut dysbiosis in the recipient mice. In parallel with gut dysbiosis correction, liver damage was partly ameliorated in the recipient mice. Gut barrier dysfunction, endotoxemia, TLR4 pathway induction as well as downstream inflammatory response and ROS overproduction were also partly suppressed due to gut dysbiosis correction in alcohol-fed recipient mice. In summary, these results suggest that gut dysbiosis correction contributes to the hepatoprotective effects of TQE against alcohol through the gut-liver axis.

Thymus quinquecostatus Celak. ameliorates cerebral ischemia-reperfusion injury via dual antioxidant actions: Activating Keap1/Nrf2/HO-1 signaling pathway and directly scavenging ROS.

BACKGROUND: Thymus quinquecostatus Celak. has been widely used as a spice and a folk medicine for relieving exterior syndrome and alleviating pain in China. PURPOSE: To explore the protective effects and the underlying mechanism against cerebral ischemia-reperfusion injury (CIRI) of the T. quinquecostatus combining with its chemical composition. STUDY DESIGN AND METHODS: High-polar extract (HPE) was extracted from T. quinquecostatus and polyphenols in HPE were enriched to obtain polyphenol-rich fraction (PRF) using Macroporous resin. The free radicals and zebrafish embryos were used to compare the antioxidant activities of HPE and PRF in vitro and in vivo. Then, the transient middle cerebral artery occlusion (tMCAO) model was established in rats. Neurological deficit score, infarction rate, morphology and apoptosis of neurons were examined to investigate the protective effects of PRF on CIRI. The mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) and the activities of downstream antioxidant enzymes in ischemia tissues were determined to clarify the underlying mechanisms. Also, reactive oxygen species (ROS) level in zebrafish embryos were detected after incubation with PRF for a short time (2 h) to investigate whether PRF could directly eliminate free radicals. Finally, chemical composition of PRF were analyzed to investigate the material basis for antioxidant activity and anti-CIRI effect. RESULTS: Compared with HPE, PRF showed stronger antioxidant activities. PRF exhibited obvious protective effects including ameliorating neurological deficit, lowering infarction rate, and improving the cellular morphology in hippocampus CA1 and cortex after tMCAO. TUNEL staining suggested PRF dose-dependently improved the apoptosis of the neurons in ischemic cortex. RT-qPCR and Western Blot results suggested that PRF regulated oxidative stress (OS) via activating the Keap1/Nrf2/HO-1 signaling pathway. Also, PRF could directly scavenge excessive ROS in zebrafish embryos after a short-time PRF incubation. The anti-CIRI effect might be primarily attributed to the abundant polyphenols in PRF, including flavonoids, polymethoxylated flavonoids, flavonoid glycosides, and phenolic acids. CONCLUSION: T. quinquecostatus contains abundant polyphenols and exhibited a good protective effect against CIRI via dual antioxidant mechanisms, providing a reference for further research and application for this plant.

Rapid discrimination and screening of volatile markers for varietal recognition of Curcumae Radix using ATR-FTIR and HS-GC-MS combined with chemometrics.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumae Radix (Yujin) has a long medicinal use history in China, which is used to cure diseases like jaundice, cholelithiasis caused by dampness-heat of gallbladder and liver, and so on. It comes from the dried tuberous roots of C. kwangsiensis (Guiyujin), C. longa (Huangyujin), C. phaeocaulis (Lvyujin) and C. wenyujin (Wenyujin). Though there are differences in chemical compositions and pharmacological activities among the four species of Yujin, they have not been differentiated well in clinical application due to their similar morphological characterizations. AIM OF THE STUDY: In this study, the four species of Yujin were rapidly and accurately discriminated. The potential volatile markers for varietal recognition were identified. MATERIALS AND METHODS: Attenuated total reflection fourier transformed infrared (ATR-FTIR) spectroscopy combined with chemometrics was used to rapidly discriminate the four species of Yujin. Headspace-gas chromatography-mass spectrometry (HS-GC-MS) technology coupled with chemometrics was employed to characterize volatile profiling, differentiate species and select potential markers for varietal recognition of Yujin. RESULTS: By applying PCA (principal components analysis) and HCA (hierarchical cluster analysis), HS-GC-MS realized complete differentiation of the four species of Yujin, while ATR-FTIR only recognized Guiyuijin. Back propagation neural network (BP-NN), KNN (K-nearest neighbor) and LDA (linear discriminant analysis) models based on spectral data achieved 100% discriminant accuracies. Support vector machines (SVM), KNN and PLS-DA (partial least square discriminant analysis) models based on volatile compounds also realized 100% discriminant accuracies. Additionally, the potential volatile markers for varietal recognition of Yujin were screened using PLS-DA, including 2 for Guiyujin, 6 for Lvyujin, 9 for Wenyujin and 13 for Huangyujin. CONCLUSIONS: The present study developed reliable methods for the varietal discrimination and volatile compounds characterization of Yujin, which will provide references for its quality control and clinical efficacy.

An integrated approach to uncover anti-tumor active materials of Curcumae Rhizoma-Sparganii Rhizoma based on spectrum-effect relationship, molecular docking, and ADME evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumae Rhizoma-Sparganii Rhizoma (CR-SR), an ancient and classical herbal couple, has been extensively used for tumor treatment in clinic of traditional Chinese medicines (TCMs). AIM OF THE STUDY: The study aimed to uncover the anti-tumor active materials of CR-SR water decoction (CR:SR = 1:1) via an integrated approach of spectrum-effect relationship, molecular docking, and ADME evaluation. MATERIALS AND METHODS: The anti-tumor activities toward A549, HepG2, Hela, BGC-823, and MCF-7 cells of the different polar elution fractions (DPEFs) of CR, SR, and CR-SR were determined by Cell Counting Kit-8 (CCK-8) assay. Likewise, the DPEFs' combinations of CR and SR were also tested. The chemical fingerprints of these fractions were profiled by HPLC. Meanwhile, HPLC-ESI-Q-TOF-MS/MS was applied for the identification of chemical components. The main effect-related compounds were screened out by spectrum-effect relationship and molecular docking method. The oral bioavailability and druggability of these active components were subsequently evaluated. Finally, five monomeric compounds were validated experimentally using HepG2 cells. RESULTS: The 80% ethanol elution fraction of CR, SR, and CR-SR showed strong anti-tumor effects toward five cells. Also, the combinations with the 80% ethanol elution fraction of CR and SR showed stronger tumor inhibition effects among the DPEFs' combinations of CR and SR. By spectrum-effect relationship, HPLC-MS, and molecular docking analysis, 24 main effect-related compounds seemed to have potential anti-tumor effects. ADME evaluation showed rutin performed low oral bioavailability and druggability. Therefore, we suppose that 23 compounds (including 4 unknown compounds) are the primary anti-tumor active components of CR-SR water decoction. Among them, zederone, curcumol, chlorogenic acid, calycosin, and curcumenol were validated successfully with good tumor inhibition effects. CONCLUSIONS: In summary, this study demonstrated that the multi-components of CR-SR contribute to its anti-tumor effects. It established a rapid and useful strategy to explore the active material basis of traditional Chinese herbal couples with a multi-technology integrated approach in practice, including chromatography, mass spectrometry, machine algorithm models, online databases, and in vitro cell experiments.

Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut-Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation.

Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut-liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.

High performance liquid chromatography fingerprint and headspace gas chromatography-mass spectrometry combined with chemometrics for the species authentication of Curcumae Rhizoma.

Curcumae Rhizoma (Ezhu), a multi-origin Chinese medicine, originates from the dry rhizomes of C. kwangsiensis, C. phaeocaulis and C. wenyujin. The three species have great variation in chemical components and therapeutic effects. To improve safety and effectiveness in clinical use, a strategy integrating chromatographic analysis and chemometrics for the species authentication of Ezhu was proposed. Firstly, systematic analysis of chemical compositions in Ezhu was achieved using high performance liquid chromatography (HPLC) fingerprint and headspace gas chromatography-mass spectrometry (HS-GC-MS). HPLC fingerprints showed that seventeen peaks in common for C. kwangsiensis and eleven peaks in common for C. wenyujin both presented a good similarity (> 0.9, only several samples < 0.8). Eleven common peaks in C. phaeocaulis and the similarity values of most samples were higher than 0.700. Additionally, there were ten common peaks in all Ezhu samples and they had relatively poor similarity with the correlation coefficients ranging from 0.364 to 0.881. For HS-GC-MS, thirty-six volatile components were identified in the three species of Ezhu, mainly monoterpenes and sesquiterpenes. Subsequently, chemometrics including unsupervised principal component analysis (PCA), supervised linear discriminant analysis (LDA), K-nearest neighbors (KNN), back propagation neural network (BP-NN) and orthogonal partial least squares-discrimination analysis (OPLS-DA) was applied to extract useful information from chromatographic profiles. Based on HPLC fingerprint data, PCA could hardly differentiate Ezhu with the three species, and LDA, KNN and BP-NN models provided more than 85 % correct identification. With HS-GC-MS data, PCA could only distinguish C. wenyujin from the other two species, and LDA, KNN, BP-NN and OPLS-DA models achieved excellent classification with 100 % accuracy. Finally, five volatile components (eucalyptol, humulene, ß-elemene, (+)-2-bornanone and linalool) with variable importance for the projection (VIP) values higher than 1 in the OPLS-DA model were selected as potential chemical markers for the species authentication of Ezhu. And the constructed OPLS-DA model using these markers obtained 100 % accuracy. Consequently, a rapid, precise and feasible strategy was established for the discrimination and quality control of Ezhu with different species.

UV spectroscopy and HPLC combined with chemometrics for rapid discrimination and quantification of Curcumae Rhizoma from three botanical origins.

Curcumae Rhizoma (Ezhu in Chinese) is a multi-origin herbal medicine with excellent clinical efficacy. For fast discrimination and quantification analysis of Ezhu from three botanical origins (Curcuma kwangsiensis, Curcuma phaeocaulis, and Curcuma wenyujin), ultra-violet (UV) spectroscopy and high performance liquid chromatography (HPLC) combined with chemometric tools were employed in this study. Firstly, the analysis method for the simultaneous determination of eleven compounds in Ezhu was developed by HPLC, and the UV spectra of thirty-eight batches of Ezhu were acquired. Then, principal component analysis (PCA), an unsupervised pattern recognition method, was applied on the HPLC and UV spectral data. PCA did not show a clear separation between C. phaeocaulis and C. wenyujin samples with HPLC data. By contrast, the supervised techniques, decision tree (DT) and linear discriminant analysis (LDA), achieved the complete discrimination for the three species of Ezhu with 100 % correct classification rate (CCR), showing excellent performance. Based on UV spectral data, PCA presented good performance for discriminating the three species of Ezhu. LDA, support vector machine (SVM) and k-nearest neighbors (KNN) models provided 96.3 % CCR for the calibration set and 100 % CCR for the validation set. Moreover, the partial least squares (PLS) and back propagation-artificial neural network (BP-ANN) quantitative models established on UV spectral data were satisfactory in predicting the contents of zederone, curdione and 3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane. The residual predictive deviation (RPD) for zederone, curdione and 3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane of PLS models were 3.169, 1.502 and 1.735, and that of BP-ANN models were 3.467, 2.481 and 2.370, respectively. The present work proposed a rapid and reliable method for the discrimination of Ezhu from three botanical origins and the prediction of zederone, curdione and 3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane contents in Ezhu, which will help a lot in the quality control of Ezhu and other multi-origin herbal medicines.

Fast discrimination and quantification analysis of Curcumae Radix from four botanical origins using NIR spectroscopy coupled with chemometrics tools.

Curcumae Radix (Yujin) is a multi-origin herbal medicine with excellent clinical efficacy. For fast discrimination and quantification analysis of Yujin from four botanical origins (Guiyujin, Huangyujin, Lvyujin and Wenyujin), near infrared (NIR) spectroscopy combined with chemometrics tools was employed in this study. Based on NIR data, principal component analysis (PCA) could only realize the separation between Guiyujin and Wenyujin samples, and the partial least squares-discrimination analysis (PLS-DA), support vector machine (SVM) and k-nearest neighbors (KNN) models achieved the complete discrimination of the four species of Yujin with 100% accuracy. Moreover, the method for the simultaneous determination of six bioactive compounds in Yujin was developed by HPLC. Germacrone, curdione and curcumenol could be found in all samples, and curcumin, demethoxycurcumin and bisdemethoxycurcumin were only observed in Huangyujin samples. Then, the support vector machine regression (SVMR) model for the prediction of germacrone content was successfully constructed. And the coefficients of determination were 0.88 and 0.89 for calibration and validation sets, respectively. The present work proposes a quick, economic and reliable method for the discrimination of Yujin from four botanical origins and the prediction of germacrone content, which will contribute to its quality control researches.

Sparganii Rhizoma: A review of traditional clinical application, processing, phytochemistry, pharmacology, and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Sparganii Rhizoma (SR), a traditional Chinese medicine (TCM), is the rhizome of Sparganium stoloniferum Buch.-Ham. mainly distributed in East Asia. It has been used for eliminating blood stasis, promoting the flow of Qi, removing the retention of undigested food and relieving pain in China for hundreds of years. AIM OF THE REVIEW: This review summarizes comprehensive information in traditional clinical application, processing, phytochemistry, pharmacology, quality control and toxicity of SR, in exploring future scientific and therapeutic potentials. MATERIALS AND METHODS: Pertinent information was systematically collected from several electronic scientific databases (e.g., Web of Science, PubMed, China Knowledge Resource Integrated, Springer, Elsevier, ScienceDirect, and Google Scholar), PhD and MS dissertations, and classic Chinese medical books. RESULTS: SR is a gynecological drug which is often used to treat dysmenorrhea, mass in the abdomen, amenorrhea due to blood stasis, and abdominal distension in TCM. Two kinds of processed products of SR are included in Chinese Pharmacopoeia, which have better pharmacological effects than the crude herb. Approximately 180 compounds have been identified from SR, including phenylpropanoids, flavonoids, anthraquinones, organic acids, alkaloids, steroids, volatile oils, diarylheptanes, etc. The crude extracts and isolated components of SR have been reported to have anti-tumor, antithrombotic, estrogen antagonistic , anti-inflammatory, analgesic, antioxidant, anti organ fibrosis and other pharmacological activities. SR also has reproductive toxicity. CONCLUSIONS: As an important TCM, SR has been demonstrated by modern pharmacological researches to have significant bioactivities, especially on anti-tumor, antithrombotic, and estrogen antagonistic activities. These activities provide prospects for the development of new drugs and therapeutics for future applications. Nevertheless, quality control and evaluation, in-depth pharmacological mechanism, and toxicological effect of SR require further detailed research.

Physicochemical Aspects and Sensory Profiles as Various Potential Factors for Comprehensive Quality Assessment of Nü-Er-Cha Produced from Rhamnus heterophylla Oliv.

Nü-Er-Cha, produced from the leaves of Rhamnus heterophylla Oliv., is known as an herbal tea and used in the treatment of bleeding, irregular menstruation and dysentery. A method was developed for the quality assessment of herbal tea, Nü-Er-Cha, adopting physical parameters, chemical constituents and sensory profiles as various potential factors. Their inner relationship was mined by multivariate statistical analysis tools, and the three factors were integrated by a technique for order preference by a similarity to ideal solution (TOPSIS) approach to comprehensively analyze the characters of Nü-Er-Cha. Viscosity was also introduced to the physical parameter determination besides conductivity, pH and color. Seven common peaks of eight batches of Nü-Er-Cha were marked by a high performance liquid chromatography (HPLC) fingerprint. They were further identified by HPLC mass spectrometry/mass spectrometry (HPLC-MS/MS) as hydroxybenzoic acids and flavanol glycosides. Fifty trained members participated in the sensory evaluation. Significant correlations between total sensory scores and conductivity, viscosity as well as pH were observed, a relatively innovative result for the quality assessment of herbal teas. The common peaks, belonging to hydroxybenzoic acids and flavanol glycosides, were mainly related to the color of infusions and leaves. The result of the TOPSIS analysis showed that S3 and S4 ranked as the top two in the comprehensive quality assessment. This may be related to rhamnetin triglycoside with a galactose/glucose and two rhamnoses, which had a higher peak response in S3 and S4 than that in the other samples. The present study may contribute to a better understanding of the relationship regarding physical properties, chemical composition and sensory profiles, and it may supply ideas for the comprehensive quality assessment of the herbal tea Nü-Er-Cha.