Cerebral vasorelaxant material basis of Xiaoxuming decoction study with rat basilar artery

OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chinese Natural Product Database(http://pharmdata.ncmi.cn).By using microvessel tension system,we checked the vasorelaxanteffects of Xiaoxuming decoction anti-cerebral ischemia effective components group(XXMDECG)and the available composition compounds on pre-contracted basilar artery ring.RESULTS963 compoundsin the decoction,including 81Fangfeng,77 Mahuang,130 Shengjiang,31 Guizhi,91 Huangqin,127 Renshen,73 Chuanxiong,44 Shaoyao,39 Xingren,42 Fangji,62 Fuzi and 166 Gancao were collected.The five largest number classes of compounds in the decoction are volatile oil(32%),flavone(32%),alkaloid(13%),saponin(7%),polyphenol and organic acid(5%).XXMDECG at concentration from 1 to 400μg·mL-1can dilate the KCl(60 mmol·L-1)and ET-1(0.01μmol·L-1)pre-contracted rat basilar artery rings in a dose-dependent manner.There are 6 compounds with vasorelaxant ratio more than 50%at the concentration of 10μmol·L-1.CONCLUSION Xiaoxuming decoction contains abundant chemical structure.It has the material basis of multiple ingredients and multiple targets.The XXMDECG are able to dilate the rat basilar artery rings in a dose-dependent manner.The network interactions between varies of chemical compounds in Xiaoxuming decoction and the vasoconstriction associated targets result in the comprehensive regulation mechanisms of vascular function.

Research Progress on Material Basis,Pharmacological Effect and Clinical Application of Danggui Shaoyao Powder

The research of modern pharmacology displays that main material basis of Danggui Shaoyao Powder exerting efficacy includes ligustilide,paeoniflorin,poria acid,ferulic acid,ligustrazine and so on,and its efficacy is mainly realized by regulating neural receptor-ligand interaction,cytokine release,and TNF-αinflammatory pathway.Systematic study of metabonomics,serum pharmacochemistry and network pharmacology of Danggui Shaoyao Powder sufficiently clarifies its potential pharmacodynamic mechanism,and it could provide scientific theoretical basis for its clinical application.In this paper,by systemically analyzing material basis of Danggui Shaoyao Powder,and exploring its complex pharmacological mechanism and clinical application in vivo,it could comprehensively understand the clinical value of Danggui Shaoyao Powder,so as to provide beneficial reference for further development of the material basis,quality control and classical prescription of Danggui Shaoyao Powder.

System pharmacology-based dissection of the potential effective material basis and mechanism of Xiaoxianxiong decoction for type 2 diabetes mellitus

Background:Xiaoxianxiong decoction is a classic formula in traditional Chinese medicine used to treat type 2 diabetes mellitus and proven to be effective.But the material basis and underlying mechanisms remain unclear.The aim of the present study was to elucidate the potential effective material basis of Xiaoxianxiong decoction and molecular mechanism treating type 2 diabetes mellitus.Methods:The absorbed bioactive components were identified based on serum pharmacochemistry.Network analysis were performed to obtain effect targets for docking verification with the absorbed prototypes to determine the potential effective material basis.On the above basis,network pharmacology was conducted to explore the molecular mechanism.Results:76 compounds were identified of Xiaoxianxiong decoction and 61 absorbed bioactive compounds were investigated.Serine/threonine kinase 1 and ALB were key targets acquired by network analysis for molecular docking.Subsequently,5 compounds were considered as the potential effective material basis,namely berberine,berberrubine,lariciresinol and gingerenone A,jatrorrhizine.Further,the mechanism mainly lies in the insulin signaling pathway,HIF-1 signaling pathway,PI3K-Akt signaling pathway,FoxO signaling pathway,AGE-RAGE signaling pathway in diabetic complications,phospholipase D signaling pathway to regulate blood glucose levels on target tissues as well as organs and exhibit anti-inflammatory,promote cell differentiation and cell growth,maintain oxygen homeostasis and affect the enzymes along with key metabolites.Conclusion:This integrated research strategy to investigate the treatment of Xiaoxianxiong decoction on type 2 diabetes mellitus provides valuable insights for further study and clinical practice of Xiaoxianxiong decoction.

Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

How to identify “Material basis–Quality markers” more accurately in Chinese herbal medicines from modern chromatography-mass spectrometry data-sets: Opportunities and challenges of chemometric tools

Modern chromatography-mass spectrometer(MS) technology is an essential weapon in the exploration of traditional Chinese medicines(TCMs) which is based on the "effectiveness-material basis-quality markers(Q-markers)". Nevertheless, the hardware bottleneck and irregular operation will limit the accuracy and comprehensiveness of test results. Chemometrics was thereby used to solve the existing problems: 1) The method of ‘design-modeling-optimization’ can be adopted to solve the multi-factor and multi-level problems in sample preparation/parameter setting;2) The approaches of signal processing can be used to calibrate the deviation from retention time(rt) dimension and mass-to-charge ratio(m/z) dimension in different types of instruments;3) The methods of multivariate calibration and multivariate resolution can be utilized to analyze the co-eluting peaks in complex samples. When the researchers need to capture essential information on raw data sets extracting the higher level of information on essential features, 1) The significant components which affects the drug properties/efficacy can be find by the pattern recognition and variable selection;2) Fingerprint-efficacy modeling is explored to clarify the material basis, or to screen out the Q-markers of biological significance;3) Chemometric tools can apply to integrate chemical(metabolic) fingerprints with network pharmacology, bioinformatics, omics and others from a multi-level perspective. Under these programs, the qualitative/quantitative works will achieve in chemical(metabolic) fingerprint and metabolic trajectories, which leads to an accurate reflection of "material basis and Q-markers" in TCMs. Likewise, an in-depth hidden information can be disclosed, so that the components of drug properties/efficacy will be found. More importantly,multidimensional data can be integrated with fingerprints to acquire more hidden information.

Enrichment factors of movable hydrocarbons in lacustrine shale oil and exploration potential of shale oil in Gulong Sag,Songliao Basin,NE China

The geological characteristics and production practices of the major middle-and high-maturity shale oil exploration areas in China are analyzed.Combined with laboratory results,it is clear that three essential conditions,i.e.economic initial production,commercial cumulative oil production of single well,and large-scale recoverable reserves confirmed by the testing production,determine whether the continental shale oil can be put into large-scale commercial development.The quantity and quality of movable hydrocarbons are confirmed to be crucial to economic development of shale oil,and focuses in evaluation of shale oil enrichment area/interval.The evaluation indexes of movable hydrocarbon enrichment include:(1)the material basis for forming retained hydrocarbon,including TOC>2%(preferentially 3%-4%),and typeⅠ-Ⅱkerogens;(2)the mobility of retained hydrocarbon,which is closely related to the hydrocarbon composition and flow behaviors of light/heavy components,and can be evaluated from the perspectives of thermal maturity(Ro),gas-oil ratio(GOR),crude oil density,quality of hydrocarbon components,preservation conditions;and(3)the reservoir characteristics associated with the engineering reconstruction,including the main pore throat distribution zone,reservoir physical properties(including fractures),lamellation feature and diagenetic stage,etc.Accordingly,13 evaluation indexes in three categories and their reference values are established.The evaluation indicates that the light shale oil zones in the Gulong Sag of Songliao Basin have the most favorable enrichment conditions of movable hydrocarbons,followed by light oil and black oil zones,containing 20.8×10^(8) t light oil resources in reservoirs with R_(0)>1.2%,pressure coefficient greater than 1.4,effective porosity greater than 6%,crude oil density less than 0.82 g/cm^(3),and GOR>100 m/m^(3).The shale oil in the Gulong Sag can be explored and developed separately by the categories(resource sweet spot,engineering sweet spot,and tight oil sweet spot)depending on shale oil flowability.The Gulong Sag is the most promising area to achieve large-scale breakthrough and production of continental shale oil in China.

Analysis on Therapeutic Potential and Action Mechanism of Folium Pyrrosiae Based on Biolabel Pattern

[Objectives]The therapeutic potential and action mechanism of Folium Pyrrosiae were analyzed based on the biolabel pattern.[Methods]The chemical components of Folium Pyrrosiae were analyzed by liquid chromatography-mass spectrometry(LC-MS).Ten databases,including Pubchem,CTD,BindingDB,HERB,TCMIP,ETCM,SwissTargetPrediction,SuperPred webserver,TargetNet and SEA,were used in turn to retrieve the targets of related components,and key components were obtained according to the enrichment degree of targets.The obtained targets were imported into the STRING database to obtain PPI information and screen out core targets.The DAVID database was employed to analyze KEGG pathways of core targets and obtain key pathways.A key component-core target-key pathway network of Folium Pyrrosiae was constructed by Cytoscape3.10.1 software.The obtained KEGG pathways were input into the CTD database to predict corresponding diseases,and discussion and analysis were carried out.[Results]Ten key components,30 potential targets and 10 key pathways were screened out,and they participated in many diseases,of which five diseases were mainly analyzed.[Conclusions]Folium Pyrrosiae had the characteristic of multi-component,multi-target and multi-pathway synergistic effect in the treatment of lung cancer,type 2 diabetes,atherosclerosis,liver cancer,prostate cancer and other diseases,and the therapeutic potential and action mechanism of Folium Pyrrosiae were analyzed through the biolabel pattern.This study provides a research basis for further developing new functions of Folium Pyrrosiae.

Exploring the mechanism of action of DHI on myeloproliferative neoplasms based on network pharmacology

Objective:The aim of this study is to explore the active ingredients and mechanism of action of danhong injection(DHI)in treating myeloproliferative neoplasms using network pharmacology.Methods:The TCMSP platform and relevant literature were used to search for the active ingredients and targets of Radix Salviae and Carthami Flos in DHI.Disease targets related to myeloproliferative neoplasms were obtained from the GEO database,GeneCards,and DisGeNET database.The queried component targets were normalized using the UniProt database.Potential targets were identified by constructing protein-protein interactions networks using STRING 11.5 and visualized and analyzed using Cytoscape 3.9.1.GO and KEGG analysis were performed using the Metascape platform,and visualization was done using the built-in plug-in CluoGO or SangerBox platforms with Cytoscape 3.9.1.Results:The active ingredients of DHI for treating myeloproliferative neoplasms mainly consist of flavonoids and o-benzoquinones,including quercetin,luteolin,kaempferol,stigmasterol,tanshinone iia,cryptotanshinone,beta-carotene,2-isopropyl-8-methylphenanthrene-3,4-dione,and neocryptotanshinone ii.The potential targets are JUN,TP53,STAT3,AKT1,MAPK1,RELA,TNF,MAPK14,IL6,and FOS.The relevant signaling pathways involved are mainly TNFαsignaling pathway,PI3K-Akt signaling pathway,apoptosis,IL-17 signaling pathway,cellular senescence,MAPK signaling pathway,p53 signaling pathway,JAK-STAT signaling pathway,and NF-kappa B signaling.Conclusions:DHI acts mainly through flavonoids and o-benzoquinones to treat myeloproliferative neoplasms in a multi-targeted and multi-pathway manner.

Serum Metabolomic Characteristics of Primary Dysmenorrhea Rat Model Induced by Estradiol Benzoate Combined with Oxytocin

[Objectives]To investigate the serum metabolomic characteristics of primary dysmenorrhea rat model induced by estradiol benzoate combined with oxytocin,and to reveal its material basis.[Methods]20 female SD rats were randomly divided into control group and model group.The primary dysmenorrhea rat model was established by subcutaneous injection of estradiol benzoate for 10 consecutive days and intraperitoneal injection of oxytocin on the last day.The serum samples of rats in control group and model group were collected by ultra-performance liquid chromatography(UPLC)quadrupole time-of-flight mass spectrometry(Q-TOF-MS).The differential metabolites were identified by multivariable pattern recognition method and endogenous metabolite database,and the metabolic pathways were enriched by Metaboanalyst 5.0 platform.[Results]There were significant differences in serum metabolic profiles between the two groups.A total of 36 potential biomarkers of primary dysmenorrhea including L-tyrosine,glycocholic acid,citric acid,palmitoyl carnitine and cholesterol were screened and identified,mainly involving metabolic pathways such as phenylalanine,tyrosine and tryptophan biosynthesis,glycerophospholipid metabolism,and primary bile acid biosynthesis.[Conclusions]The serum metabolic profile of primary dysmenorrhea rats deviates significantly from that of healthy rats,and there are multiple metabolic pathway disorders,which are mainly related to phenylalanine,tyrosine and tryptophan biosynthesis,glycerophospholipid metabolism,and primary bile acid biosynthesis.

Research on the potential mechanism of Huashi Baidu Recipe against novel coronavirus pneumonia(COVID-19)by network pharmacology and molecular docking technology

Objective:Use network pharmacology to explore the anti-COVID-19 mechanism of Huashi Baidu Recipe,supplemented by molecular docking verification.Methods:Thorugh databases such as TCMSP,GeneCard,String,and software such as Cytoscape,AutoDockVina,network relationships was established,and the binding ability of active ingredients and targets is calculated through molecular docking,and biological function enrichment analysis was conducted.Result:The ingredients in Huashi Baidu Recipe that had strong affinity with SARS-CoV-23CL hydrolase(3CLpro)and angiotensin converting enzyme 2(ACE2)receptors include Quercetin,Baicalein,Astragaloside IV,Wogonin and other ingredients;25 active ingredients which obtained by screening had strong affinity with targets such as IL6,IL1B,NOS2 and CCL2.The biological function enrichment analysis mainly focused on Th17,Th1 and Th2 cell differentiation,NF-κB,MAPK,TNF,IL-17signaling pathway,etc.Conclusion:The active ingredients of Huashi Baidu Recipe may inhibit the infection and replication of SARS-CoV-2 virus,regulate RAS system’balance,inhibit excessive immune inflammatory response,and prevent inflammatory storm from appearing to fight COVID-19.

Gaps and feasibility of fixed-dose combination strategy in the development of modern Chinese medicine

isTraditional Chinese medicine(TCM)is a highly complex chemical substance system,which not only reflected in the complexity of the chemical components and their interrelationships,but also in the intricacy of the prescription’s connection with the human body.Component compatibility strategy has been proposed for developing modern TCM since 2005 and established comprehensive relevant technologies and research approaches.Moreover,to meet the safety and efficacy of current pharmaceuticals,research on fixed-dose combination drugs is directed by modern scientific theories,conforms to TCM compatibility principles and clarifies material basis and pharmacological mechanisms and component-effect correlations.This review summarized gaps and feasibility of fixed-dose combination strategy in the development of modern TCM research and assessed their advantages and disadvantages in light of contemporary drug combination research practices.

Network pharmacology approaches for research of Traditional Chinese Medicines

Pharmacodynamics material basis and effective mechanisms are the two main issues to decipher the mechnisms of action of Traditional Chinese medicines(TCMs)for the treatment of diseases.TCMs,in“multi-component,multi-target,multi-pathway”paradigm,show satisfactory clinical results in complex diseases.New ideas and methods are urgently needed to explain the complex interactions between TCMs and diseases.Network pharmacology(NP)provides a novel paradigm to uncover and visualize the underlying interaction networks of TCMs against multifactorial diseases.The development and application of NP has promoted the safety,efficacy,and mechanism investigations of TCMs,which then reinforces the credibility and popularity of TCMs.The current organcentricity of medicine and the“one disease-one target-one drug”dogma obstruct the understanding of complex diseases and the development of effective drugs.Therefore,more attentions should be paid to shift from“phenotype and symptom”to“endotype and cause”in understanding and redefining current diseases.In the past two decades,with the advent of advanced and intelligent technologies(such as metabolomics,proteomics,transcriptomics,single-cell omics,and artificial intelligence),NP has been improved and deeply implemented,and presented its great value and potential as the next drug-discovery paradigm.NP is developed to cure causal mechanisms instead of treating symptoms.This review briefly summarizes the recent research progress on NP application in TCMs for efficacy research,mechanism elucidation,target prediction,safety evaluation,drug repurposing,and drug design.

Qianjin Wenwu decoction suppresses renal interstitial fibrosis by enhancing the degradation of extracellular matrix in mice with unilateral ureteral obstruction

Diabetic kidney disease(DKD)is the most common complication of diabetes mellitus(DM).Qianjin Wenwu decoction(QWD),a well-known traditional Korean medicine,has been used for the treatment of DKD,with satisfactory therapeutic effects.This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD.The results demonstrated that a total of 13 active components in five types were found in QwD,including flavonoids,flavonoid glycosides,phenylpropionic acids,saponins,coumarins,and lignins.Two key proteins,TGF-β1 and TIMP-1,were identified as the target proteins through molecular docking.Furthermore,QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction(UUO).Hematoxylin&eosin(H&E)and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice.We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF-βl in DKD treatment.These findings explain the underlying mechanism of QWD for the treatment of DKD,and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.