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.

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.

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.

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.

Evaluation of Component Activities in C-Mn-Fe-Si with Model Self-SReM4

A sub-regular solution model SELFSReM4 used to evaluate activities of the components in a homogeneous region of a quaternary system has been developed in Shanghai Enhanced Lab of Ferrometallurgy. This paper introduces the application of SELFSReM4 in evaluating activities of the components in C-Mn-Fe-Si system without SiC precipitation.

Evaluation of Component Activity in Molten MnO-SiO_(2)-Al_(2)O_(3)-CaO System with Model SELF-SReM4

A sub-regular solution model SELF-SReM4 used to evaluate activity of the components in a homogeneous region of a quaternary system has been developed in Shanghai Enhanced Laboratory of Ferrometallurgy.The application of SELF-SReM4 in C-Mn-Fe-Si system without the SiC formation has been introduced in previous paper.It’s application for molten slag of MnO-SiO2-Al2O3-CaO was introduced in this paper.They provide a basis for the prediction of the metal-slag equilibrium conditions.

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.

EVALUATION OF COMPONENT ACTIVITIES IN THE MOLTEN C_Fe-X(X=Si,Mn,Cr,Ni)SYSTEM

Expressing the excess partial molar free energies and integral excess free energy as poly- nome of the composition,then the parameters in the expression of excess partial molar free energy of C were evaluated based on:the excess partial free energy of C in C-Fe bi- nary alloy:the integral excess free energy of Fe-X binary alloy:the C saturation curve and the iso-activity curve of C (α_c=0.025) in the ternary system.Then the activity coefficient of X was evaluated with the so-called “I-D” method,by which the component activities of every element in the whole molten ternary alloy can be evaluated,and the results are in good agreement with literature data based on experiment.

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.

基于零点配置的分力合成主动振动抑制方法研究(英文)

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.