Mechanism of pachymic acid in the treatment of gastric cancer based on network pharmacology and experimental verification

BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.

Unraveling the therapeutic mechanisms of myristic acid and luteolin 7-rutinoside in oral cancer: insights from network pharmacology and molecular docking analysis

Background:The compound Luteolin-7-rutinoside(L7R)is a flavone derivative of luteolin,predominantly identified in plant species belonging to the families Asteraceae.Conversely,Myristic acid is characterized by its structure as a 14-carbon,unsaturated fatty acid.In this investigation,we endeavor to elucidate the putative mechanisms underlying the therapeutic effects of Myristic Acid and Luteolin 7-rutinoside in the context of oral cancer treatment,employing network pharmacology coupled with molecular docking methodologies.Methods:The protein targets of Myristic Acid and Luteolin 7-rutinoside were identified through a search on the Swiss Target Database.Subsequently,a compound-target network was constructed using Cytoscape 3.9.1.Targets associated with OC were retrieved from the OMIM and GeneCards databases.The overlap between compound targets and OC-related targets was determined,and the resulting shared targets were subjected to protein-protein interaction(PPI)network analysis using the STRING database.Additionally,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted on the identified targets.Molecular docking were performed to investigate the interactions between the core target and the active compound.Results:The component target network comprises 103 nodes and 102 edges.Among the proteins in the protein-protein interaction(PPI)network,those with higher degrees are TNF,PPARG,and TP53.Analysis through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways indicates that the treatment of OC with Myristic Acid and Luteolin 7-rutinoside primarily involves the regulation of miRNA transcription and inflammatory response.The identified signaling pathways include Pathways in cancer,PPAR signaling pathway,EGFR signaling pathway,and TNF signaling pathway.Molecular docking studies reveal that Luteolin 7-rutinoside and Myristic acid exhibit higher affinity towards TNF,PPARG,TP53,and EGFR.Conclusion:This study reveals the potential molecular mechanism of Myristic Acid and Luteolin 7-rutinoside in the treatment of oral cancer,and provides a reference for subsequent basic research.

Boswellic acids: a review on its pharmacological properties, molecular mechanism and bioavailability

Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of biological activities,such as anti-inflammatory,anti-cancer,antibacterial,antiviral,hepatoprotective,neuroprotective,anti-diabetic,and anti-thrombotic properties.As a result,it has gained significant recognition among practitioners of traditional Chinese and Indian medicine.These biological effects may be associated with multiple molecular targets and signal transduction pathways.However,the poor pharmacokinetic properties of the substance lead to lower bioavailability,which affects its effectiveness.To address this issue,scientists have proposed a number of strategies,such as solid dispersions,phytosome®technologies,and novel drug delivery systems.This article aims to provide a comprehensive overview for boswellic acids on the phytochemistry,molecular mechanisms,potential therapeutic applications,and strategies to improve bioavailability.

Exploring the targets and molecular mechanism of glycyrrhetinic acid against diabetic nephropathy based on network pharmacology and molecular docking

BACKGROUND Diabetic nephropathy(DN)stands as the most prevalent chronic microvascular complication of diabetes mellitus.Approximately 50%of DN patients progress to end-stage renal disease,posing a substantial health burden.AIM To employ network pharmacology and molecular docking methods to predict the mechanism by which glycyrrhetinic acid(GA)treats DN,subsequently validating these predictions through experimental means.METHODS The study initially identified GA targets using Pharm Mapper and the TCMSP database.Targets relevant to DN were obtained from the Genecards,OMIM,and TTD databases.The Venny database facilitated the acquisition of intersecting targets between GA and DN.The String database was used to construct a protein interaction network,while DAVID database was used to conducted Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)analysis.Molecular docking experiments were performed using Autodock software with selected proteins.Experimental validation was conducted using renal proximal tubular cells(HK-2)as the study subjects.A hyperglycemic environment was simulated using glucose solution,and the effect of GA on cell viability was assessed through the cell counting kit-8 method.Flow cytometry was employed to detect cell cycle and apoptosis,and protein immunoblot(western blot)was used to measure the expression of proteins of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and insulin resistance pathway,including insulin receptor(INSR),PI3K,p-PI3K,AKT,p-AKT,and glycogen synthase kinase-3(GSK3).RESULTS A total of 186 intersecting targets between GA and DN were identified,which were associated with 144 KEGGrelated enrichment pathways,375 GO biological process entries,45 GO cellular component entries,and 112 GO cellular function entries.Molecular docking demonstrated strong binding of GA to mitogen-activated protein kinase(MAPK)-1,SRC,PIK3R1,HSP90AA1,CASPASE9,HARS,KRAS,and MAPK14.In vitro experiments revealed that GA inhibited HK-2 cell viability,induced cell cycle arrest at the G2/M phase,and reduced apoptosis with increasing drug concentration.Western blot analysis showed that GA differentially up-regulated GSK3 protein expression,up-regulated AKT/p-AKT expression,down-regulated INSR,AKT,p-AKT,PI3K,and p-PI3K protein expression,and reduced p-PI3K/PI3K levels under high glucose conditions.CONCLUSION GA may protect renal intrinsic cells by modulating the PI3K/AKT signaling pathway,thereby inhibiting HK-2 cell viability,reducing HK-2 cell apoptosis,and inducing cell cycle arrest at the G0/G1 phase.

Purification Process,Content Determination,Pharmacological Activity and Molecular Mechanism of Neogambogic Acid

Neogambogic acid is characterized by broad antitumor spectrum,good antitumor effect and low toxicity and side effects.This paper reviews the purification process,content determination and pharmacologic activity of neogambogic acid,in order to provide a theoretical reference for the research and application of neogambogic acid.

Research advances in phytochemistry,pharmacology and toxicology of oleanolic acid

Oleanolic acid(OA)is a pentacyclic triterpenoid chemical component that exists in natural plants with a molecular formula of C30H48O3 and a molecular weight at 456.71 g·mol-1.OA is widespread in traditional Chinese herbal medicine(Ligustri Lucidi Fructus,Achyranthis Bidentate Radix,Red Sage)and berries(blueberries,grapes).In recent years,because of the extensive pharmacological effects of OA,its advantages in disease treatment have become increasingly prominent and gradually attracted the attention of pharmaceutical researchers.OA has effective therapeutic effects on a series of chronic diseases such as inflammation,cancer,diabetes,and cardiovascular diseases through multiple signaling pathways and various targets.Especially in cancers,such as colorectal cancer,liver cancer,gastric cancer,lung cancer,breast cancer and other malignancies,OA presents substantial efficacy.However,its poor aqueous solubility,needy bioavailability,and unsatisfactory pharmacological activity excessively restrict its clinical application.More importantly,the improper utilization of OA can cause adverse reactions,toxic effects and even damage to organs in some specific situations.With the discovery of various pharmacological effects,the complex action mechanisms of OA,the continuous progress in structural modification of OA,as well as the synthesis of OA derivatives,its application is expanding gradually.Among numerous studies,there is a clear indication that OA and its derivatives,if fully developed,may provide an alternative and cheaper treatment for a variety of chronic diseases.However,the specific molecular mechanisms of OA and its derivatives as an alternative therapy and supplementary therapy for cancer,diabetes,cardiovascular disease and other chronic diseases remain to be clarified.Therefore,it is necessary to further study the pharmacokinetics,pharmacological activity,specific targets and related mechanisms of OA to lay a solid foundation for drug development and the application of OA in clinical settings.

Pharmacologic inducers of the uric acid exporter ABCG2 as potential drugs for treatment of gouty arthritis

Uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of production and the rate of excretion,the latter occurring in urine(kidney),bile(liver)and feces(intestinal tract).Reabsorption in kidney is also an important component of this process.Both excretion and reabsorption are mediated by specific transporters.Disruption of the balance between production and excretion leads to hyperuricemia,which increases the risk of uric acid crystallization as monosodium urate with subsequent deposition of the crystals in joints causing gouty arthritis.Loss-of-function mutations in the transporters that mediate uric acid excretion are associated with gout.The ATP-Binding Cassette exporter ABCG2 is important in uric acid excretion at all three sites:kidney(urine),liver(bile),and intestine(feces).Mutations in this transporter cause gout and these mutations occur at significant prevalence in general population.However,mutations that are most prevalent result only in partial loss of transport function.Therefore,if the expression of these partially defective transporters could be induced,the increased number of the transporter molecules would compensate for the mutation-associated decrease in transport function and hence increase uric acid excretion.As such,pharmacologic agents with ability to induce the expression of ABCG2 represent potentially a novel class of drugs for treatment of gouty arthritis.

Pharmacological research progress of ursolic acid for the treatment of liver diseases

Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory,hepatoprotective,antitumor,and hypoglycemic activity.This natural product is widely present in many common Chinese herbal medicines such as Hedyotis diffusa and Prunella vulgaris.The present review highlights the pharmacological research progress of ursolic acid in liver disease,with a focus on providing directions for future research and clinical practice of ursolic acid.Modern studies have demonstrated that ursolic acid can adjust the activities of enzymes such as superoxide dismutase and NADPH oxidase to balance oxidative stress,reduce inflammation,as well as to repair damaged liver.Research also showed that ursolic acid targeted lipid metabolic genes,activating autophagy and reducing lipid deposition in hepatocytes,further preventing the progress of fatty liver.Besides,the combination of ursolic acid with caspase-3 was able to prevent apoptosis and relieve liver injury.Furthermore,ursolic acid was showed to target the intestine by alleviating mucosal injury and restoring the balance of the intestinal microecology and protect liver through the enterohepatic axis.In terms of antitumor activity,ursolic acid targeted several tumor suppressor genes including gene of phosphate and tension homology deleted on chromsome ten and p53,and affected the expression of cyclin and apoptosis-related proteins involving Bax,Bcl-2,and Bcl-x,which acted on signal transduction pathways including phosphatidylinositol-3-kinase/protein kinase B,extracellular regulated protein kinases and proteina fosforilata 21 wide-type actiated factorlp 1.The same compound interacted with caspases,resulting in inhibition of cell proliferation and induction of apoptosis.In addition,ursolic acid also exerted anticancer activity through inhibiting angiogenesis,tumor invasion and metastasis,and improving immunity.Other studies have noted the importance of nano-preparations of ursolic acid for its clinical applications.This review provides essential information on the role of ursolic acid in liver protection.Further research on the mechanisms of action of ursolic acid would be useful for its pharmaceutical development and clinical application.

Study on the effect of Danbei Yifei formula on pulmonary fibrosis based on network pharmacology and molecular docking technology

Objective:To determine the pharmacodynamic material basis and mechanism of Danbei Yifei formula on pulmonary fibrosis.Methods:Starting with the clear absorbed components of Danbei Yifei formula or the potential effective components in line with the five rules of Ribinsky,the network pharmacology method and technology of traditional Chinese medicine were used to predict and analyze the action targets of Danbei Yifei formula in vivo,such as Salvia miltiorrhiza,PINBEI,Taoren,etc.On the basis of enrichment analysis,the core pathway of Danbei Yifei formula in the treatment of pulmonary fibrosis was identified,and the binding energy of drug ligand and protein target was determined through molecular docking technology simulation and verification,and its affinity and stability were evaluated.To clarify the material basis and mechanism of Danbei Yifei formula in the treatment of pulmonary fibrosis.Result:The results of network pharmacology prediction of traditional Chinese medicine showed that Danbei Yifei formula contained 72 potential pharmacodynamic components and 26 corresponding targets,including CHRM1、MAPK14、CCL2、ADRB1、PTGS1、PPARG、ALOX5、Pde3a、CHRM2、Adrb2、TNF、JUN、Adora2a、LTA4H、CYP1A2、OPRD1、CHRM3、DRD2、OPRM1、ARG1、EDNRA、Il6st、TACR1、MMP1、MMP8、Ptgs2,which were related to pulmonary fibrosis and pulmonary fibrosis Lung related diseases are highly correlated.There were 26 Go items(P<0.05)in go functional enrichment analysis,including 22 biological process(BP),9 cellular component(CC)and 3 molecular function(MF)categories.The results of network pharmacology showed that many components,such as protocatechuic acid and aminosuccinic acid,had direct effects on known targets of pulmonary fibrosis.Conclusion:Danbei Yifei formula contains many effective components which have inhibitory effect on pulmonary fibrosis,and it may play its role through the mechanism of multi-component and multi-target synergistic effect.

Evaluation of Angelicae sinensis radix as a promising treatmentoption for hyperlipidemia based on network pharmacology

Background: Angelicae sinensis radix has been widely applied in traditional Chinese medicine while little isexplored in its potential mechanism. This study aims to elucidate the effective components and defattingmechanism based on network pharmacology. Methods: Traditional Chinese Medicine Systems PharmacologyDatabase and Analysis Platform was screened to collect the possible active ingredients and their CAS and SMILESwas searched in Pubchem, which further used for reverse molecular docking in Swiss Target Prediction database toobtain potential targets. Hyperlipidemia-related molecules were obtained from GeneCards database, and thepredicted targets of Angelicae sinensis radix for hyperlipidemia treatment were selected by Wayne diagram. Formechanism analysis, the protein-protein interactions were constructed with String, the Gene Oncology enrichmentanalysis and Kyoto Encyclopedia of Genes and Genomes analysis were conducted in DAVID. Results: Usingnetwork-based systems biology analysis, we predicted that 5 active ingredients in Angelicae sinensis radix hasantilipemic effects with 71 potential targets. Through Gene Oncology and Kyoto Encyclopedia of Genes andGenomes analysis, we found that the related signaling pathways mainly involved in arachidonic acid metabolism,and regulation of lipolysis in adipocytes. The related genes are ALOX5, CYP2C19, EPHX2, PTGS1, PTGS2,ADRB1, and ADRB3. Conclusion: Angelicae sinensis radix may alleviate hyperlipidemia through arachidonic acidmetabolism, and regulation of lipolysis in adipocytes. ALOX5, CYP2C19, EPHX2, PTGS1, PTGS2, ADRB1, andADRB3 may be new targets for treatment.

Investigating mechanism of Jiang-zhi-dai-pao-cha for treatment of hyperlipidemia by network pharmacology

Objective:To collect the main components and targets of Jiang-zhi-dai-pao-cha(JZDPC)and investigate the mechanism of JZDPC for the treatment of hyperlipidemia by network pharmacology.Methods:The components and targets of JZDPC were searched from ETCM databases,the targets related to hyperlipidemia were searched from DisGeNET and GeneCards databases,and then the intersection targets and corresponding key components were obtained.Cytoscape 3.8.2 software was used to construct and analyze networks,and then Metascape online database was applied for gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of core putative targets.Results:There were 99 overlapping targets between JZDPC and hyperlipidemia,among which NR3C1,ESR1,NR1I2,NFKB1,ESR2,ALOX5,PTGS1,PPARA,RXRA,LPL,PLA2G1B,PYGM,CYP2C9 were the core putative targets,and many members of nuclear receptor 1(NR1)subfamily were included.The core components of JZDPC,such as Ursolic Acid,β-Sitosterol,Resveratrol,Arirubic Acid,Alisol A,Oleanolic Acid,Rhein,Chrysophanol and Emodin,can regulate blood lipid by regulating a series of signaling pathways including the above core potential targets,such as non-alcoholic fatty liver disease(NAFLD)signaling pathway,pathways in cancer,arachidonic acid(AA)metabolism signaling pathway and peroxisome proliferator activated receptor(PPAR)signaling pathway,Starch and sucrose metabolism signaling pathway,etc.They play many roles in the treatment of hyperlipidemia by participating in lipid synthesis and metabolism,anti inflammation,anti oxidative stress,regulating hormone levels and carbohydrate metabolism.Conclusion:Network pharmacology provides a theoretical basis for investigating the mechanism of action of JZDPC,and the NAFLD signaling pathway is one of the most valuable pathways.

Mechanism of Wumei Pill in the Treatment of Non-Erosive reflux disease from the Perspective of Network Pharmacology and Molecular docking

Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei Pill by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and collected NERD related targets through Genecards,PharmGKB,Drugbank,DisGeNET,OMIM,CTD and TTD databases.Intersection targets of Wumei Pill targets and NERD related targets were the potential targets of Wumei Pill in the treatment of NERD.We imported the intersection targets into the STRING database to obtain the PPI network,and obtained the hub targets.The network diagram of"Drugs-Potential active ingredients-Potential targets"was constructed by Cytoscape 3.7.2 software.We used R software to perform Gene Ontology function enrichment analysis(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis(KEGG)on hub targets,and then performed molecular docking verification.Results:There were 129 active ingredients and 213 drug targets of Wumei Pill of which 114 were the intersection targets.1587 GO enrichment items were identified(P<0.05),including 1,491 biological processes,11 cell components,and 85 molecular functions.143 KEGG pathways(P<0.05),mainly related to Kaposi sarcoma-associated herpesvirus infection,IL-17 signaling pathway,the TNF signaling pathway,MAPK signaling pathway.Results of molecular docking showed that the potential active ingredients in Wumei Pill had relatively stable binding activity to the key targets.Conclusion:Wumei pill for the treatment of non-erosive reflux disease are main active ingredients quercetin,kaempferol,beta sitosterol,Isocorypalmine,Stigmasterol,rutaecarpine,etc,the main targets is JUN,TP53,AKT1,may inhibit excessive inflammation,antioxidant therapy effect into full play.This provided a certain theoretical basis for clinical application.

基于网络药理学与体外实验探讨茯苓酸治疗心肌纤维化的作用机制

目的:基于网络药理学与体外验证实验探讨茯苓酸治疗心肌纤维化(myocardial fibrosis,MF)的作用机制。方法:借助SwissTargetPrediction、GeneCards等数据库预测茯苓酸、氧化应激及MF靶点,取三者交集靶点于STRING数据库构建蛋白互作(PPI)网络,借助Cytoscape 3.7.2软件进行可视化分析,筛选出核心靶点,使用Metascape数据库进行GO和KEGG富集分析,预测茯苓酸治疗MF的作用机制,采用分子对接技术及大鼠心肌成纤维细胞(cardiac fibroblasts,CFs)实验加以验证。结果:预测发现,茯苓酸潜在靶点164个、氧化应激靶点3040个、MF靶点4441个,三者交集靶点84个,涉及Bcl-2、PTGS2、Bcl-2L1、MMP-2等9个核心靶点。GO分析发现,生物过程主要作用于抗氧化活性、对缺氧的反应。KEGG分析显示,茯苓酸治疗MF的主要信号通路为PI3K/Akt。分子对接结果显示,茯苓酸与Bcl-2、PTGS2、Bcl-2L1、MMP-2等9个核心靶点均具有良好的结合活性。体外实验结果显示,茯苓酸(5、10、20μmol/L)能显著抑制CFs迁移能力(P<0.01),降低ROS、MDA水平(P<0.05),升高SOD水平(P<0.05),下调CollagenⅠ、CollagenⅢ、MMP-9、MMP-2、PTGS2 mRNA水平(P<0.05)和CollagenⅠ、CollagenⅢ、α-SMA蛋白表达(P<0.05),上调PI3K、Akt、Bcl-2、Bcl-2L1 mRNA水平(P<0.05)和p-PI3K、p-Akt蛋白表达(P<0.05)。采用PI3K抑制剂(LY294002)后,茯苓酸对CFs细胞中ROS、SOD、MDA、CollagenⅠ、CollagenⅢ、α-SMA、p-PI3K、p-Akt作用被逆转(P<0.05)。结论:表明茯苓酸能够抑制CFs氧化应激损伤和心肌纤维化,该作用与其调控PI3K/Akt信号通路密切相关。

基于网络药理学与实验验证探讨肉桂酸治疗慢性心力衰竭的作用机制

目的采用网络药理学、分子对接及体外实验验证的方法,探讨肉桂酸治疗慢性心力衰竭(chronic heart failure,CHF)的潜在靶点及作用机制。方法通过网络药理学在线数据库预测肉桂酸靶点及CHF靶点,取交集靶点于String数据库构建蛋白互作网络,通过Cytoscape 3.7.2软件进行可视化分析,筛选出核心靶点,使用Metascape数据库进行GO和KEGG富集分析,预测肉桂酸治疗CHF的作用机制,采用分子对接技术及体外实验验证上述结果。结果网络药理学分析结果发现,肉桂酸潜在靶点187个,与6094个CHF疾病靶点相交,得到132个交集靶点,涉及CASP3、JUN、PTGS2、MMP9、TLR4等10个核心靶点。GO和KEGG富集分析显示,肉桂酸治疗CHF的作用主要与细胞对活性氧的反应、对氧化应激的反应等生物过程有关,涉及细胞凋亡等信号通路。分子对接结果显示,肉桂酸与10个核心靶点均具有良好的结合活性。体外实验结果显示,肉桂酸能显著降低心肌细胞H9c2凋亡率及活性氧水平(P<0.05),降低c-Jun、PTGS2、MMP9、TLR4 mRNA表达水平(P<0.05)和caspase-9、caspase-3、Bax蛋白表达水平(P<0.05),升高Bcl-2蛋白表达水平(P<0.05);使用乙酰半胱氨酸后,细胞凋亡率、活性氧水平及Bax蛋白表达水平显著降低(P<0.05),Bcl-2蛋白表达水平显著升高(P<0.05),与肉桂酸作用一致。结论肉桂酸能够调节多个信号靶点、抑制心肌细胞氧化应激损伤及细胞凋亡,发挥治疗CHF的作用,肉桂酸是苓桂术甘汤防治CHF的重要物质基础之一。

基于网络药理学与脂质组学探讨迷迭香酸缓解食物过敏的效应机制

为研究迷迭香酸缓解食物过敏的效应机制,利用网络药理学和分子对接以及脂质组学探究迷迭香酸(Rosmarinic acid,RA)缓解食物过敏的效应机制。利用数据库分析平台(TCMSP)、Swiss Target Prediction、Pharm Mapper、Super Pred和Gene Cards等获得RA的潜在效应靶点。通过软件Cytoscape和String数据库构建“活性成分-靶点”蛋白互作(PPI)网络,并采用AutoDockTools软件进行分子对接验证。进一步通过建立卵清蛋白(Ovalbumin,OVA)食物过敏小鼠模型验证RA缓解食物过敏的效应,并基于高分辨质谱对小鼠血清进行脂质代谢分析。结果表明,网络药理分析共筛选到关联靶点46个。基因本体(Geno ontology,GO)富集分析表明RA主要通过对蛋白质磷酸化、鞘糖脂、磷脂和类固醇等的结合发挥作用。京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析表明关联靶点主要富集在Th1和Th2细胞分化通路、脂代谢和炎症性肠病通路等。动物实验结果显示RA干预可以显著(P<0.05,P<0.01,P<0.001)抑制OVA致敏引起的小鼠血清过敏反应介质上升,且RA干预组小鼠血清总胆固醇(Total Cholesterol,T-CHO)和甘油三酯(Triglyceride,TG)水平下降。脂质组学分析中,在正/负离子模式下分别筛选出25/36种潜在差异脂质代谢物。对脂质差异代谢物的富集分析表明,小鼠的血清脂质代谢影响甘油磷脂代谢和鞘脂代谢通路。因此,本研究表明RA主要通过调节脂质代谢和机体炎症反应发挥缓解食物过敏的作用。

齐墩果酸对B淋巴细胞损伤的保护作用并基于网络药理学探索其作用机制

目的:研究齐墩果酸对B淋巴细胞损伤的保护作用并基于网络药理学方法阐明其作用机制。方法:在实验第1~5天每天给昆明小鼠腹腔注射环磷酰胺80 mg/kg以建立免疫抑制动物模型。从造模第6天开始每天给予25 mg/kg齐墩果酸处理,连续28 d作为干预组,同时设置模型组和空白组作为对照。采用流式细胞术检测各组小鼠的骨髓B淋巴细胞亚群百分率。为探索齐墩果酸的作用机制,进一步使用PubChem数据库获得齐墩果酸的化学结构,用SwissTargetPrediction数据库预测齐墩果酸的药物靶点,通过String平台对潜在的药物靶点进行蛋白质相互作用网络分析、基因本体(GO)生物过程富集分析和京都基因与基因组百科全书(KEGG)信号通路富集分析。结果:在给药28 d后,模型组的成熟B细胞亚群(IgD与B220双阳性细胞)百分率为(2.585±0.248)%,明显低于空白组的(8.235±0.361)%,差异具有统计学意义(P<0.01),说明免疫抑制动物模型成功建立;而齐墩果酸干预组的成熟B细胞亚群百分率为(3.395±0.445)%,明显高于模型组,差异具有统计学意义(P<0.01)。通过SwissTargetPrediction数据库筛选到PTPN1、CD81等齐墩果酸的潜在药物靶点。经String平台分析和Cytoscape绘图计算后,连通性排名前5的节点蛋白有PPARG、PTGS2、PPARA、MAPK3和HMGCR。通过GO生物过程富集分析及KEGG信号通路分析得出,齐墩果酸的药理作用富集于脂质储存的负调控等生物过程及B细胞受体(BCR)信号通路。结论:齐墩果酸能够增加骨髓成熟B细胞亚群的百分率,其机制可能是通过影响BCR信号通路在B淋巴细胞的发育过程中发挥作用。

菊苣酸治疗代谢性疾病药理作用研究进展

代谢性疾病是一类由物质或能量代谢异常引起的全身多系统代谢异常的疾病,包括糖尿病、肥胖、非酒精性脂肪性肝病、高脂血症、痛风等。代谢性疾病的病因与遗传、饮食、运动、衰老和环境等众多因素相关,其病程发展缓慢不易察觉且发病后难以治愈,已经成为全球主要的公共卫生问题。从天然化合物中寻找治疗代谢性疾病的有效药物具有重要意义。菊苣酸为蒲公英、菊苣等多种天然药用植物中的重要活性成分,现代药理学研究表明,菊苣酸在抗炎、抗氧化、平衡糖脂代谢、降尿酸、肝脏保护等方面具有显著的生物活性。本文通过汇总国内、外相关文献,全面综述了菊苣酸在治疗糖尿病、肥胖、非酒精性脂肪性肝病、高脂血症、痛风相关代谢性疾病的研究进展,旨在为菊苣酸治疗代谢性疾病药理作用的深入研究提供参考。

基于网络药理学和分子对接技术探究川芎抗肝纤维化的作用机制

为探究川芎抗肝纤维化的活性成分及作用机制。本研究采用网络药理学方法,采用GEO数据库及DisGeNET数据库检索获取肝纤维化靶点;利用TCMSP数据库及文献检索获取川芎化学成分及作用靶点;将川芎药物靶点与疾病靶点取交集,并进行蛋白互作网络构建及拓扑分析;采用DAVID数据库进行GO和KEGG富集分析,利用微生信进行做图;通过Cytoscape软件构建“成分-靶点-信号通路”调控网络。采用分子对接技术针对川芎活性成分和关键靶点进行对接模拟。结果表明,TCMSP数据库检索结合文献研究,筛选得到川芎中8个活性成分及对应的88个作用靶点;GEO数据库筛选及DisGeNET数据库检索获取疾病靶点2038个,交集得到32个川芎治疗肝纤维化的共同靶点,并筛选出转录激活因子3(Signal transducer and activator of transcription 3,STAT3)、前列腺素内过氧化物合成酶2(Recombinant prostaglandin endoperoxide synthase 2,PTGS2)和表皮生长因子受体(Epidermal growth factor receptor,EGFR)等关键靶点。富集分析表明,川芎治疗肝纤维化的靶点主要参与肝癌信号通路、脂质代谢和动脉粥样硬化、白介素17信号通路和内分泌抵抗等信号通路,涉及RNA聚合酶Ⅱ启动子转录的正向调节过程和信号转导过程等生物学过程。“成分-靶点-信号通路”分析表明,川芎抗肝纤维化活性成分6个,分别为阿魏酸(Ferulic acid,FA)、川芎哚(Perlolyrine)、叶酸(Folic acid)、川芎萘呋内酯(Wallichilide)、亚麻油酸乙酯(Mandenol)和肉豆蔻酮(Myricanone),其中阿魏酸的节点度值最大。分子对接结果表明,川芎抗肝纤维化关键成分阿魏酸和关键靶点PTSG2、MMP9和EGFR分子均具有较好的结合能力,结合能分别为-23.04kJ/mol、-22.17kJ/mol和-25.14kJ/mol。川芎可通过靶向STAT3、PTGS2和EGFR等靶点,调控肝癌和脂质代谢等信号通路,改善肝纤维化病变,发挥保护肝脏的作用。

山楂酸药理作用的研究进展

山楂酸是一种五环三萜类化合物,广泛存在于油橄榄和山楂等多种天然植物中。山楂酸具有抗肿瘤、抗炎、抗氧化、抗菌、心血管保护、神经保护等药理作用。针对山楂酸的药理活性研究进展及其作用机制进行综述,为其进一步开发和应用提供参考依据。

基于网络药理学、分子对接探讨熊果酸治疗缺血性脑卒中的分子机制

目的运用网络药理学、分子对接方法,挖掘熊果酸(ursolic acid,UA)治疗缺血性脑卒中的作用靶点及其潜在的分子机制。方法通过中药系统药理学数据库与分析平台及SwissTargetPrediction数据库对UA进行靶点预测,在Gene Cards数据库中获取缺血性脑卒中的靶点,并构建UA-缺血性脑卒中交叠靶点,通过String平台构建交叠靶点蛋白互作(protein-protein interaction,PPI)网络图,应用Cytoscape 3.9.1软件对PPI网络图进行拓扑属性分析,筛选出关键靶点后,进行基因本体论(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,最后进行靶点-UA分子对接进行验证。结果共筛选得到UA相关靶点122个和3509个缺血性脑卒中靶点;获得UA-缺血性脑卒中交叠靶点98个及19个关键靶点;其中白细胞介素-6(interleukin 6,IL-6)、肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-1β(interleukin 1β,IL-1β)、信号转导及转录激活因子3(signal transducers and activators of transcription,STAT3)、过氧化物酶体增殖激活受体γ(peroxisome proliferative activated receptor gamma,PPARG)是排名前5的核心靶点;KEGG通路富集分析结果显示关键靶点主要富集在血脂和动脉粥样硬化、TNF信号通路、白细胞介素17(interleukin 17,IL-17)信号通路、晚期糖基化终末产物-受体(advanced glycation end products-receptor for advanced glycation end products,AGE-RAGE)信号通路;GO功能富集分析显示关键靶点主要涉及转录因子活性、神经元凋亡过程的正向调节、炎症反应等过程;分子对接结果显示UA和排名前5的核心靶点可以稳定的结合,结合能均小于0 kcal/mol。结论UA可能通过调节IL-6、TNF、IL-1β、STAT3、PPARG影响血脂和动脉粥样硬化、TNF信号通路、IL-17信号通路、AGE-RAGE信号通路,发挥抗炎、神经保护等作用,以治疗缺血性脑卒中。