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.

Analysis of Active Components of Hexane Extractives of Morus alba Leaves

[Objective]The aim was to explore the active compound of Morus alba leaves with the analysis of active components of hexane extractives of M.alba leaves.[Method]Antibacterial assays of hexane extractives of M.alba leaves were done and the volatile components of hexane extractives of M.alba leaves with the strongest antibacterial activity were analyzed by gas chromatography-mass spectrometry（GC-MS）.[Result]The results of inhibitory effect of hexane extractives of M.alba leaves on Staphylococcus aureus and Escherichia coli showed that hexane extractives of M.alba leaves collected in June,July and August had antibacterial activity against S.aureus and had no antibacterial effect against E.coli.Furthermore,hexane extractives of M.alba leaves collected in June had the strongest antibacterial activity against S.aureus（inhibition diameter 10.95 mm）.The hexane extractives of M.alba leaves collected in June was analyzed by GC-MS,the main volatile components were tetradecane（16.76%）,dodecane（13.20%）,diisobutyl phthalate（10.26%）,decane（9.10%）,hexadecane（8.71%）,linolenyl alcohol（7.25%）,octadecane（5.88%）,eicosane（3.26%）,dibutyl phthalate（2.59%）.[Conclusion]Linolenyl alcohol was the potential antibacterial compound.

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.

EFFECTS OF S86019, AN ACTIVE COMPONENT FROM PURALIA LOB AT A, ON CELL DIFFERENTIATION AND CELL CYCLE TRAVERSE OF HL-60 CELLS

The effects of S86019, an active component from Puralia lobata, on the induction of cell differentiation and cell cycle traverse of HL-60 cells were described. It was shown that cell proliferation of HL-60 cells was inhibited by S86019 in vitro. Under the action of S86019 the HL-60 cells were induced to differentiate into metamyelocytes, myelocytes and much matured cells with banded or segmented nucleus. Flow cytometry demonstrated that the cell population of HL-60 cells was blocked at G1 phase which resulted in the elevation of percentage of G1 cells and decrease of percentage of cells in S phase. Experimental results demonstrated that S86019 is an active inducer of cell differentiation in HL-60 cells.

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.

Effects of Different Cultivation Media and Periods on the Content of Main Active Components of Cordyceps militaris Strain QC04

In this study,Cordyceps militaris strain QC04 was cultivated in oat,rice,and wheat media for different time periods.We studied the effects of different cultivation media and periods on the fruiting body biomass and active components of C.militaris,aiming to provide reference for the production and utilization of C.militaris QC04.The results showed that the dry weight of the fruiting body of C.militaris was the highest in the wheat medium,moderate in the oat medium,and the lowest in the rice medium.The content of cordycepin and adenosine in the fruiting body and residual medium was higher in the oat and rice media than in the rice medium.The content of cordycepin and adenosine in fruiting body and residual medium peaked on day 55.Furthermore,the content of cordycepin in the fruiting body was lower than that in the residual medium,while the content of adenosine showed an opposite trend.The content of cordycepic acid in the rice medium was generally higher than that in the oat and wheat media.As the cultivation period extended,the fruiting body biomass declined and the content of cordycepic acid in the fruiting body increased slightly.

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.

Study on Component Synthesis Active Vibration Suppression Method Using Zero-placement Technique

The component synthesis active vibration suppression method （CSVS） can be applied to suppress the vibration of flexible systems. By this method, several same or similar time-varying components are arranged according to certain rules along the time axis. The synthesized command can suppress the arbitrary unwanted vibration harmonic while achieving the desired rigid body motion. The number of the components increases rapidly when the number of harmonic vibration is growing. In this article, the CSVS based on zero-placement technique is used to construct the synthesized command to suppress the multi-harmonics simultaneously in the discrete domain. The nature of zero-placement method is to put enough zeros to cancel system poles at necessary points. The designed synthesized command has equal time intervals between each component and which is much easier to be implemented. Using this method, the number of components increases linearly with the increasing of the number of being suppressed harmonics. For the spacecraft with flexible appendages, CSVS based on zero-placement is used to design the time optimal large angle maneuver control strategy. Simulations have verified the validity and superiority of the proposed approach.

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.

Antiplatelet Effect of Active Components Derived from Chinese Herbal Medicine

Atherothrombosis is the major cause of acute coronary syndromes and cardiovascular deaths.Platelets participate in the processes of forming and extending atherosclerotic plaques.Therefore,antiplatelet therapy is a milestone in the primary and second prevention of atherothrombotic diseases.Along with the longterm use of antiplatelet agents,the safety and drug resistance has become a big concern in clinic and new drugs possessing higher effectiveness and fewer adverse effects are needed.Abundant recent data support that traditional Chinese herbs may be a good alternative and complementary choice of new antiplatelet drugs.This review highlights the progress of antiplatelet effect of active components derived from traditional Chinese herbs based on their chemical structures.

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.

Quantitative Metabolomics:Analysis on Active Components in Extracts from Kaki Folium

Objective In order to analyze the active components in the extracts from Kaki Folium(KF),quantitative metabolomics approach was adopted to investigate the number of active components existing among the different extracts and their variation.Methods LC-MS method was established for the quantitative determination of the active components taking the mixture with reference substance as tested sample.Results In terms of the number of active components and amount presented in the different tested samples of KF extracted by many types of solvents,variation was observed.But rutin,astragalin,and kaempferol were presented in all samples.Difference was found between the samples extracted from the products on market and from the raw materials of KF processed by polar solvents with different recipes.However,the three active components were found in all samples examined.Conclusion These results might be valuable as all information and could be used for the optimization of raw materials extraction procedure to enhance the productivity.

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

Chemical composition of Galla chinensis extract and the effect of its main component(s) on the prevention of enamel demineralization in vitro

To determine the chemical composition of Galla chinensisextract （GCE） by several analysis techniques and to compare the efficacy of GCE and its main component（s） in inhibition of enamel demineralization, for the development of future anticaries agents, main organic composition of GCE was qualitatively determined by liquid chromatography-time of flight-mass spectrometry （LC-TOF-MS） and quantified by high-performance liquid chromatography-diode array detector （HPLC-DAD）. Inorganic ions were tested by inductively coupled plasma-atomic emission spectroscopy and F was especially measured by ion chromatography. Then, bovine enamel blocks were randomly divided into four treatment groups and were subjected to a pH-cycling regime for 12 times. Each cycle included 5-min applications with one of four treatments： 4g.L-1 GCE solution, 4g.L-1 gallic acid （GA） solution, I g.L-1 NaF solution （positive control）, deionized water （DDW, negative control）, and then 60-min application in pH 5.0 acidic buffer and 5-min application in neutral buffer. Acidic buffers were retained for calcium analysis. The main organic composition of GCE were GA and its isomer, and, to a lesser extent, small molecule gallotannins. The content of GA in GCE was 71.3%±0.2% （w/w）. Inorganic ions were present in various amounts, of which Ca was （136±2.82） μg.g-1, and Zn was （6.8±0.1） μg.g-1. No F was detected in GCE. in pH cycling, GA showed an effect similar to GCE in inhibiting enamel demineralization （P〉0.05）. GA was found to be the main effective, demineralization inhibiting component of GCE and could be a promising agent for the development of anticaries agents.

Determination of anthraquinone prodrug and its hydrolytically active compounds using RP-HPLC

In order to study the hydrolytic characterization of an anti-inflammatory prodrug （ RI-1 ） in vitro, an effective, accurate and reliable method for the simultaneous determination of the prodrug and its two hydrolytic active compounds is developed using reverse phase high-performance liquid chromatography （RP-HPLC）. The chromatographic separation is performed on an ODS-2 C18 column （250 mm × 4. 6 mm, 5.0 μm particle size） with a simple elution program. The mobile phase is V（ methanol） ： V（0. 1% phosphoric acid solution） =90：10 （adjust pH to 2. 3）. A wavelength of 225 nm and a mobile phase flow rate of 1.0 mL/min are utilized for the quantitative analysis. Excellent linear behaviors over the investigated concentration ranges are observed with values of R2 higher than 0. 999 for all the analytes. The validated method is successfully applied to the simultaneous determination of the prodrug and its active components can be used to detect hydrolytic characterization in vitro.