Active components of Bupleuri Radix in the treatment of schizophrenia analyzed by network pharmacology and clinical verification

Background:Bupleuri Radix is a common Chinese medicinal material in traditional Chinese medicine.Currently,the therapeutic effect of treating schizophrenia is relatively well understood.However,there are fewer studies examining the underlying mechanisms of its treatment.The objective of the study was to investigate the primary mechanisms of Bupleuri Radix in treating schizophrenia through network pharmacology and clinical validation.Method:Network pharmacology revealed possible molecular mechanisms,followed by clinical verification.Sixty-seven schizophrenia patients undergoing treatment at the Hunan Brain Hospital between October and November 2022 were recruited and randomly divided into the olanzapine group and the olanzapine+Bupleuri Radix group.Additionally,32 healthy people undergoing physical examinations during the same period were included as the control group.The patient’s positive and negative symptom scale scores were compared.qPCR was used to detect the mRNA expression levels of ESR1,mTOR,EIF4E,and SMAD4 in peripheral blood.Results:Through network pharmacological analysis,it was concluded in this study that Bupleuri Radix might regulate the mTOR,PI3K-Akt,and HIF-1 signaling pathways.Clinical experiments indicated that compared with before treatment,the positive and negative symptom scale scores and total scores of the two treatment groups were significantly decreased after treatment(P<0.01).In addition,the positive and negative symptom scale scores and total scores in the olanzapine+Bupleuri Radix group were significantly decreased(P<0.01)compared to the olanzapine group after treatment.Before treatment,ESR1 mRNA expression levels in peripheral blood were significantly higher in the two treatment groups than in the control group,whereas the mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly lower(P<0.01).The mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly higher after therapy than before treatment,whereas the mRNA expression levels of ESR1 in peripheral blood were significantly lower(P<0.01).After therapy,the olanzapine+Bupleuri Radix group’s mRNA expression levels of mTOR,EIF4E,and SMAD4 were significantly higher than those of the olanzapine group,whereas the mRNA expression levels of ESR1 were significantly lower(P<0.01).Conclusion:The mechanism of Bupleuri Radix’s therapeutic efficacy in schizophrenia may involve the up-regulation of mTOR,EIF4E,and SMAD4 mRNA expression and the down-regulation of ESR1 mRNA expression in peripheral blood.

Research Progress of Natural Active Components against Damage from UV Radiation

The sun's ultraviolet(UV)rays are extremely harmful to the skin.In addition to causing sunburn and aging,excessive UV radiation can also lead to benign or malignant skin tumors.This paper reviews the researches on natural active components against damage from UV radiation,and summarizes the types of compounds,research methods and mechanisms of action.Moreover,the main problems in current research are put forward,and the possible development direction in the future is discussed.

Network Pharmacology-based Research of Active Components of Albiziae Flos and Mechanisms of Its Antidepressant Effect

Albiziae Flos(AF)has been experimentally proven to have an antidepressant effect.However,due to the complexity of botanical ingredients,the exact pharmacological mechanism of action of AF in depression has not been completely deciphered.This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF.The methods included collection and screening of chemical components,prediction of depression-associated targets of the active components,gene enrichment,and network construction and analysis.Quercetin and 4 other active components were found to exert an tidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand・wceptor interaction pathways.DRD2,HTR1 A,and SLC6A4 were identified as important targets of the studied bioactive components of AF.This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.

LW-AFC and its active components ameliorate corticosterone-induced long-term potentiation impairment in mice

OBJECTIVE LW-AFC is extracted from the classical traditional Chinese medicinal prescription-Liuwei Dihuang Decoction.Previous studies have showed that LW-AFC could improve learning&memory ability in amny animal models.In this study,we focused on evaluating the effect of several main active components fromLW-AFC(B-B;loganin,LOG;morroniside,MOR;paeoniflorin,PF and stachyose,STA)on LTP.METHODS In vivo recording of LTP was used in this study to evaluate the effects of LW-AFC and it′s active components on coticorsterone(Cort)induced LTP impairment.RESULTS The results showed that LW-AFC could ameliorate Cort-induced LTP impairment.The effect of LW-AFC was abolished when the immune function was inhibited.Single administration(ig,ip,icv)of any of the components had no effect on Cort-induced LTP impairment.Consecutively intragastric administration or intraperitoneal injections(chronic administration)of B-B,LOG,MOR or PF for 7 d showed protective effect on Cort-induced LTP impairment.Intragastric administration of STA for 7 d protected LTP from impairment induced by Cort,while there was little improving effect when STA was administrated via intraperitoneal injection.In addition,when the intestinal microbiota was disrupted by applying the antibiotic cocktail,STA showed little protective effect against Cort.CONCLUSION In conclusion,LW-AFC and it′s components showed positive effects against cort induced LTP impairment,it seems that all displayed protective effects via indirectly,immune modulation might be the common pathway for all components;the exact pathways are different in each component,B-B,LOG,MOR and PF could be absorbed into the bloods tream and then modulate the peripheral immune function,while STA could not be absorbed and modulates the immune function via modulating intestinal microbiota.Further studies are needed to invesgate the underlying mechanisms and the synergetic effects of all components.

Determination of Active Components of Lamiophlomis rotata(Benth.)Kudo by Ultra-performance Convergence Chromatography

[Objectives]To determine active components of Lamiophlomis rotata(Benth.)Kudo.[Methods]A new method was developed for the quantitative determination of L.rotata by using Ultra-performance convergence chromatography.The separation of active components of L.rotata was successfully achieved on Waters ACQUITY UPC column,with gradient elution carbon dioxide and methanol solvent at flow rate of 0.7 mL/min.The separation gradient elution rate was as follows:15%methanol 0-1 min,18%methanol 1-5 min,20%methanol 5-6 min,25%methanol 6-7 min,30%methanol 7-8 min,30%methanol 8-9 min,15%methanol 9-10 min.The conditions used in the separation process was as follows:column temperature 30℃;injection volume 2μL.Under the abovementioned conditions,the content of methyl glucoside was measured by 3D-full wavelength scanning.The validity of the method was tested by analyzing the precision,reproducibility,stability and accuracy.[Results]The results indicated that in terms of extraction and separation of compounds,supercritical CO2 not only has the diffusion property of gas,but also has the density and fluidity of liquid.[Conclusions]The ultra-high performance chromatography is a new technique for drug analysis.

Changes in Active Components before and after Microorganism Fermentation of Rhizoma Paridis(Chonglou)

[Objectives] To study the changes in active components before and after microorganism fermentation of Rhizoma Paridis( Chonglou). [Methods]Analytical methods using total saponins and total flavonoids as indicators were established. UV spectrophotometry was used to determine the changes in active components before and after fermentation of Rhizoma Paridis. [Results] The content of total saponins decreased after fermentation,while the content of total flavonoids increased. [Conclusions]The content of total saponins decreased after fermentation and the content of total flavonoids increased. The fermentation process of Monascus purpureus Went. needs further optimization.

Biological Active Components of Selected Medical Fungi

According to official data, about 2000 mushrooms belong to the category of medical mushrooms, while over 600 have already confirmed medical properties. The aim and task of this work were to collect, analyze and process scientific and expert data of biologically active components of selected Basidiomycetes fungi: Letinula edodes, Ganoderma Lucidum, Grifola frondosa, Trametes versicolor and Inonotus obliquus. Areas of fungi therapy and the search for new immunomodulatory agents are far from being restricted to these species alone, however, these five may serve as typical representatives of widespread medicinal fungi used in both traditional medicine and modern biomedical research. Their biologically active components have different pharmacological effects, and beta-glucan polysaccharides, which are recognized as immunomodulators, are of particular importance. Many of the fungal beta-glucans tested have switched to pharmaceuticals such as Lentinan, Sonifilan, Krestin and GanoPoly, which speaks to their pharmacological and research potential. Citing the results of scientific advances in the last two decades, the results of preclinical tests and the results of clinical studies can confirm that supplementation with medical fungi can increase treatment success or mitigate the negative side effects of different therapies. A long-term weakened immune system is a risk factor for malignancies, so it can be concluded that disease prevention is beneficial for each individual and deserves the same attention paid to treating the disease.

Community Structure of Endophytic Fungi in Ginseng and Its Correlation Analysis with Active Components

[Objectives]The paper was to explore the correlation between active components of ginseng and community structure of endophytic fungi in ginseng under different cultivation methods.[Methods]Using ginsengs under two main planting patterns in Huanren County,Liaoning Province as the samples,the community structure of endophytic fungi was studied by molecular means,and the chemical components were identified and the content of chemical markers was measured via LC-MS.Moreover,the correlation between medicinal components of ginseng and diversity of endophytic fungal flora was analyzed.[Results]The diversity and active components of endophytic fungi of ginseng were different.The diversity analysis showed that the medicinal components of ginseng were positively correlated with some fungal groups in ginseng.[Conclusions]Artificial intervention in the planting process would affect the endophytic fungi in medicinal materials,and further affect the chemical components of ginseng medicinal materials.

Recent advances in screening active components from natural products based on bioaffinity techniques

Natural products have provided numerous lead compounds for drug discovery.However,the traditional analytical methods cannot detect most of these active components,especially at their usual low concentrations,from complex natural products.Herein,we reviewed the recent technological advances(2015-2019)related to the separation and screening bioactive components from natural resources,especially the emerging screening methods based on the bioaffinity techniques,including biological chromatography,affinity electrophoresis,affinity mass spectroscopy,and the latest magnetic and optical methods.These screening methods are uniquely advanced compared to other traditional methods,and they can fish out the active components from complex natural products because of the affinity between target and components,without tedious separation works.Therefore,these new tools can reduce the time and cost of the drug discovery process and accelerate the development of more effective and better-targeted therapeutic agents.

Accurate construction of cell membrane biomimetic graphene nanodecoys via purposeful surface engineering to improve screening efficiency of active components of traditional Chinese medicine

Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane(CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications that can avoid the aggregation of nanocarriers while maintaining the biological activity of CM remains a challenge. Herein, a high-performance CM biomimetic graphene nanodecoy was fabricated via purposeful surface engineering, where polyethylene glycol(PEG) was used to modifying magnetic graphene oxide(MGO) to improve its stability in physiological solution, so as to improve the screening efficiency to active components of traditional Chinese medicine(TCM). With this strategy, the constructed PEGylated MGO(PMGO) could keep stable at least 10 days, thus improving the CM coating efficiency. Meanwhile, by taking advantage of the inherent ability of He La cell membrane(HM) to interact with specific ligands, HM-camouflaged PMGO showed satisfied adsorption capacity(116.2 mg/g) and selectivity. Finally, three potential active components, byakangelicol, imperatorin,and isoimperatorin, were screened from Angelica dahurica, whose potential antiproliferative activity were further validated by pharmacological studies. These results demonstrated that the purposeful surfaceengineering is a promising strategy for the design of efficient CM biomimetic nanomaterials, which will promote the development of active components screening in TCM.

Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis

Objective:To screen the active components from Fuzheng Huayu Recipe(FZHY)and redesign a new recipe composed of the active components,and validate the effect of active components formulation from FZHY against liver fibrosis.Methods:Thirty-two components from FZHY were evaluated for their activities against liver fibrosis respectively,with 6 kinds of cell models in vitro,including oxidative stressed hepatocyte in L-02,hypoxia injured/proliferative hepatic sinusoidal endothelial cells in SK-HEP-1 and human hepatic sinusoidal endothelial cells(HHSEC),and activated hepatic stellate cell in LX-2.The comprehensive activity of each component against liver fibrosis was scored according to the role of original herbs in FZHY and cell functions in fibrogenesis.Totally 7 active components were selected and combined with equal proportion to form a novel active components formulation(ACF).The efficacy of ACF on liver fibrosis were evaluated on activation of LX-2 and proliferation of HHSEC in vitro and in liver fibrosis model mice induced by dimethylnitrosamine(DMN).Totally 72 mice were divided into6 groups using a random number table,including normal,high-dose ACF control(20μmol/L×7 components/kg body weight),model,low-,medium-,high-dose ACF groups(5,10,20μmol/L×7 components/kg body weight,respectively).Hematoxylin eosin and Sirius red stainings were used to observe inflammation and fibrosis change of liver tissue;scanning electron microscopy(SEM)and transmission electron microscopy(TEM)were utilized to observe the effect of ACF on ultrastructure of hepatic sinusoids.Results:Fifteen components from FZHY showed higher scores for their activity on against liver fibrosis.Among them,7 components including tanshinoneⅡA,salvianolic acid B,cordycepin,amygdalin,quercetin,protopanaxatriol,and schizandrin B were recombined with equal proportions to form ACF.ACF at 1,2,4μmol/L showed strong inhibitory effects on activation of LX-2 and proliferation of HHSEC in vitro(all P<0.01).Compared with the model group,ACF attenuated liver collagen deposition,improved sinusoidal capillarization in a dose-dependent manner(all P<0.05).Conclusions:ACF exerts a satisfactory effect against experimental liver fibrosis and attenuates sinusoidal capillarization,which warrant a further research and development for herbal components formulation on liver fibrosis.

ACCELERATED DISCOVERY AND PROFILING OF PHYSIOLOGICALLY ACTIVE COMPONENTS IN COMPLEX SAMPLES BY HPTLC-EDA-HRMS

On the one hand,the separation of thousands of compounds in a complex extract is thrilling,but may be still be separated unsatisfactorily.Hence,the question arises where to stop in high-sophisticated separation science?Which technical effort is economically justifiable in routine?On the other hand,the separation itself does not imply an effect-directed answer to questions such

A comprehensive review on the effects of green tea and its components on the immune function

Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of action.In contrast,the effects and mechanisms of tea and its components on the immune system are rarely reviewed.The study aimed to review the most potent compounds in tea that affect the immune systems and mechanisms associated with it.As a result of in vitro studies,animal models,and human trials,researchers have found that green tea extracts and compounds have the possibility of modulating the innate immune system,adaptive immune system,and intestinal immune system.In immune-related diseases,tea polyphenols are the most significant compounds that modify immune functions,though other compounds are being investigated and cannot be ruled out.The review provides a new perspective on how the immune-regulatory effects of tea and its components are exerted on immune systems,as well as how they affect the emergence and treatment of diseases.

Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid

Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of pneumonia.However,the pharmacological components of GC for pneumonia treatment are rarely explored.Gan An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many years.Therefore,GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia.We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days.Using the intelligent mass spectrometry data-processing technologies to analyze the metabolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in urine.After analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective components.The experimental results based on two animal pneumonia models and the inflammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo.The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS.Thus,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.

Bioactive Constituents of the Seed Kernels from Vernicia fordii

A new compound,(2′R)-(5-oxo-2,5-dihydrofuran-2-yl)methyl octanoate(1),together with 9 known ones(2-10)were isolated from the bioactive extract of the seed kernels from Vernicia fordii.Their structures were determined by spectroscopic analyses,including Nuclear Magnetic Resonance(NMR)and High Resolution Electrospray Ionization Mass Spectroscopy(HRESI-MS).Their cytotoxicities against three human cancer cell lines(A549,HepG2 and Caco2 cells)and anti-neuroinflammatory effects were evaluated.Cytotoxicity assay revealed that compound 9 could inhibit the growth of HepG2 cells,while compound 6 had a moderate inhibitory effect against A549 cells.Further anti-neuroinflammatory activity assay showed that compound 10 exhibited moderate inhibitory effect on the release of NO in LPS-stimulated BV2 microglia cells.

Study on Quality Markers of Poria cocos Based on UPLC-Q-TOF-MS and Network Pharmacology Technology

[Objectives]To analyze the main chemical components of traditional Chinese medicine(TCM)Poria cocos by liquid chromatography-mass spectrometry,and explore the active components for P.cocos in the treatment of primary dysmenorrhea(PD)by network pharmacology to predict its quality markers(Q-marker).[Methods]Ultra performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry(UPLC-Q-TOF-MS)in positive and negative ion mode was used to collect high quality MS and MS/MS data of Poria cocos,and qualitative characterization of the components in Poria cocos was performed using Analyst TF 1.7.1 and PeakView 2.2 software with reference to internal databases and literature.Taking the above identified chemical components as the research object,we used network pharmacology to discover the potential effective components and their key targets of PD,and metabolic pathway enrichment analysis of the core targets was performed to screen the Q-marker of P.cocos based on the five principles of Q-marker of TCM.[Results]UPLC-Q-TOF-MS technique was used to identify 41 chemical components of P.cocos,including 3 amino acids,26 triterpenoids,4 lactones,7 organic acids and 1 adenosine.It was more likely to lose H 2O and CO 2 during cleavage and break at the carbonyl group.The triterpenoids were mainly in the form of[M-H]-peaks in negative ion mode,which was easy to lose some structural fragments such as H 2O,CH 3COOH,CH 4,CO 2,etc.Further network pharmacological analysis showed that 302 targets of chemical components of P.cocos,518 targets of PD,28 common targets of component and disease,and 27 core targets such as PTGS2,ESR1,TNF,IL1B were observed by PPI interactions network analysis.451 biological processes such as hormone response and inflammatory response regulation were obtained by GO enrichment analysis.KEGG enrichment analysis showed that 89 pathways including PI3K/Akt signaling pathway,IL-17 signaling pathway and TNF signaling pathway were obtained.The connectivity value of components was analyzed.The core components with the connectivity value greater than 10,including poricoic acid A,polyporenic acid,polyporenic acid C,and 25-hydroxy-3-epidehydrotumoric acid were selected,while the key targets with the connectivity value greater than 15 included TNF,PTGS2,IL1B and CASP3.Molecular docking between core components and key targets was performed,and most of the docking energy was less than-5 kcal/mol,indicating that the binding between the active components and target proteins of P.cocos was relatively stable,so 23 active components of P.cocos were determined.Following the five principles of Q-marker,four possible Q-markers of P.cocos were predicted,including poricoic acid A,pachymic acid,polyporenic acid C,and 25-hydroxy-3-epidehydrotumoric acid.[Conclusions]P.cocos was mainly composed of triterpenoids,its effect on the treatment of PD may be achieved mainly by poricoic acid A,pachymic acid,polyporenic acid C,and 25-hydroxy-3-epi-dehydrotumoric acid acting on PTGS2,ESR1,TNF,IL1B and other targets to regulate PI3K/Akt signaling pathway,IL-17 signaling pathway,TNF signaling pathway,etc.Based on these active components,poricoic acid A,pachymic acid,polyporenic acid C,and 25-hydroxy-3-epi-dehydrotumoric acid could be taken as Q-markers of P.cocos,which provided a solid basis for further improving the quality standard of P.cocos.

Study of the anti-inflammatory effect of the Traditional Mongolian Medicine Hohgardi-9 in acute lung injury

Background:Hohgardi-9 is a well-known traditional Mongolian drug that relieves cough and removes phlegm.Although it is widely used to treat lung diseases clinically,Hohgardi-9’s bioactive constituents and mechanism of action are unknown.In this study,we explored the bioactive compounds in Hohgardi-9 and the mechanism underlying its therapeutic effect against acute lung injury(ALI).Methods:We obtained the main components of Hohgardi-9 and analyzed the targets related to ALI by searching the traditional Chinese medicine systems pharmacology database and existing literature.Then,we constructed the compound-target network using Cytoscape 3.8.0 software to obtain the bioactive compounds in Hohgardi-9 against ALI.We used a string database to investigate the interaction between the possible protein targets of Hohgardi-9.We also performed Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict its anti-ALI mechanism.Further,to verify the therapeutical effects of Hohgardi-9,we used an ALI rat model and analyzed the components of Hohgardi-9 found in the rat plasma using ultra-high-performance liquid chromatography coupled with Q-Exactive mass spectrometry.Results:The network pharmacology and plasma component analysis showed that Hohgardi-9 contained 31 potentially bioactive components,including quercetin,herbacetin,izoteolin,and columbinetin acetate,which affected the NF-κB,TLR,and TNF signaling pathways via key targets,such as RELA(p65)and TLR4.The in vivo experiments using hematoxylin and eosin staining revealed that Hohgardi-9 significantly improved lung tissue injury and pulmonary edema in ALI rats.Simultaneously,Hohgardi-9 significantly reduced the expression levels of genes encoding inflammatory factors,such as TRL4,TNF-α,IL-1β,and ICAM1,in the lungs of ALI rats.Conclusion:Hohgardi-9 alleviated ALI by inhibiting inflammation-related gene expression through its active ingredients,such as quercetin and herbacetin.

Analysis of Pharmacodynamic Substance Basis of Fufang Changtai in Treating Colorectal Cancer by UPLC-Q-TOF-MS Combined with Network Pharmacology

[Objectives] To systematically study the main active components of Fufang Changtai(FFCT) in the treatment of colorectal cancer(CRC), and to explore its mechanism of action. [Methods] The main chemical components of FFCT were analyzed by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) combined with automatic analysis platform, and the main pharmacodynamic substances of FFCT were studied by network pharmacology method and its mechanism of action was explored. The binding degree between the active components and the core targets were verified by molecular docking technology. [Results] A total of 86 compounds were identified from FFCT, among which 26 compounds were Ginsenoside Rg3, Ginsenoside Rb1, Astragaloside III, etc. The key target pathway enrichment analysis showed that FFCT played its role in the treatment of CRC mainly through the PI3K-Akt signaling pathway and MAPK signaling pathway. [Conclusions] This study comprehensively identified the FFCT components. Supplemented by network pharmacology and molecular docking technology, it is expected to provide a scientific theoretical basis and an important reference for FFCT therapeutic components identification, key target verification and mechanism of action in the treatment of CRC.

鉴定植物天然产物生物活性组分的新方法（英文）

Countless studies have been devoted to the scientific evaluation of the safety and/or efficacy of botanical natural products.Investigators involved in such studies face a unique set of challenges.Natural products differ from their pharmaceutical counterparts in that they are typically complex mixtures,for which the identities and quantities of components present are not known.To further complicate matters,the composition of these mixtures will vary depending on source material and method of preparation.Investigators conducting clinical trials with complex botanical natural products must choose from a myriad of potential preparations,which may vary greatly in composition.In making such decisions,it is extremely useful to know which components of the mixture are most likely to be responsible for its purported biological activity(the"active constituents").The gold standard approach for identifying active constituents of botanical natural products is bioassay-guided fractionation,in which the mixture is subjected to successive rounds of purification and bioassays until an active compound is identified.Bioassay guided fractionation has historically played a critical role in drug discovery,but is,nonetheless,fraught with challenges.The process is biased towards the most abundant and easily isolatable mixture components,which may not be the most biologically active.Furthermore,if multiple compounds contribute either additively,antagonistically,or synergistically to the observed biological activity of the mixture,activity may be lost upon isolation.As a complementary strategy to bioassay-guided fractionation,our research group has developed untargeted metabolomics strategies to aid in the identification of bioactive mixture components.These strategies involve profiling botanical mixtures using ultraperformance chromatography coupled to high resolving power mass spectrometry.The resulting chemical data is then integrated with biological assay data using biochemometric data analysis strategies.Several case studies will be presented illustrating how this approach can be applied,including for the identification of compounds from the botanical green(Camellia sinensis)that inhibit drug metabolizing enzymes.Such studies are being conducted as part of the Center for Excellence in Natural Product Drug Interaction Studies(Na PDI),which is supported by a cooperative agreement with the National Center for Complementary and Integrative Health,a component of the National Institutes of Health.

Mechanism of Pinelliae Rhizoma in Treatment of Insomnia Based on Network Pharmacology

[Objectives]To explore the mechanism of Pinelliae Rhizoma in the treatment of insomnia.[Methods]Using the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database,the effective components of Pinelliae Rhizoma were explored,to predict its targets,and screen out the targets of insomnia through GeneCards,OMIM and other databases.With the aid of Cytoscape software,a"component-target-pathway-disease"network for the treatment of insomnia by Pinelliae Rhizoma was built.Then,a target protein-related interaction network was created through the String database,and biological function annotation and pathway analysis of key targets were performed.[Results]The 13 active components of Pinelliae Rhizoma take action in the treatment of insomnia by intervening 33 targets,59 GO biological processes,and 10 main biological pathways.[Conclusions]The active components of Pinelliae Rhizoma may treat insomnia by such pharmacological effect as regulating G protein-coupled amine receptor activity,adrenergic receptor activity,catecholamine binding,and neurotransmitter receptor activity.