人参皂苷Rg3对糖尿病视网膜病变大鼠PI3K-Akt/PKB通路和血管内皮生长因子、细胞间黏附分子-1表达的影响

目的研究人参皂苷Rg3对糖尿病视网膜病变大鼠PI3K-Akt/PKB通路和血管内皮生长因子(vascular endothelial growth factor,VEGF)、细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)表达的影响。方法将60只SD大鼠随机分为对照组、模型组、人参皂苷Rg3治疗高剂量组(H-Rg3组,5.0 mg·kg^-1 Rg3)、低剂量组(L-Rg3组,0.5 mg·kg^-1 Rg3),每组各15只,构建糖尿病视网膜病变大鼠模型,共治疗28 d。检测各组大鼠视网膜组织中丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)和乳酸脱氢酶(lactate dehydrogenase,LDH)表达;HE染色和TUNEL染色分析病理变化;免疫组织化学检查ICAM-1和VEGF蛋白的表达;Western blot检测视网膜组织中PI3K、Akt、p-Akt蛋白的表达;采用LY294002抑制剂(静脉注射,0.5 mg·kg^-1)验证PI3K-Akt/PKB通路。结果与对照组相比,模型组凋亡细胞比例、视网膜组织中MDA和LDH表达均升高(均为P<0.05),SOD、PI3K和p-Akt蛋白表达均降低(均为P<0.05),VEGF、ICAM-1、Bad、cleaved-Caspase-3蛋白表达均升高(均为P<0.05)。与模型组相比,L-Rg3组和H-Rg3组凋亡细胞比例、视网膜组织中MDA和LDH表达均降低(均为P<0.05),SOD、PI3K和p-Akt蛋白表达均升高(均为P<0.05),VEGF、ICAM-1、Bad、cleaved-Caspase-3蛋白表达均降低(均为P<0.05)。与L-Rg3组相比,H-Rg3组凋亡细胞比例、视网膜组织中MDA和LDH表达均降低(均为P<0.05),SOD、PI3K和p-Akt蛋白表达均升高(均为P<0.05),VEGF、ICAM-1、Bad、cleaved-Caspase-3蛋白表达均降低(均为P<0.05)。与LY-模型组相比,LY294002组VEGF、ICAM-1、Bad和cleaved-Caspase-3蛋白表达均升高(均为P<0.05),Bcl-2蛋白表达降低(P<0.05)。与LY-Rg3组相比,LY-Rg3+LY294002组VEGF、ICAM-1、Bad和cleaved-Caspase-3蛋白表达均升高(均为P<0.05),Bcl-2蛋白表达降低(P<0.05)。结论人参皂苷Rg3能够通过激活PI3K-Akt/PKB信号通路,下调VEGF和ICAM-1蛋白的表达,保护糖尿病视网膜病变大鼠的视网膜组织。

Chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway

Ketamine, a rapid-acting antidepressant drug, has been used to treat major depressive disorder and bipolar disorder(BD). Recent studies have shown that ketamine may increase the potential risk of treatment-induced mania in patients. Ketamine has also been applied to establish animal models of mania. At present, however, the underlying mechanism is still unclear. In the current study, we found that chronic lithium exposure attenuated ketamine-induced mania-like behavior and c-Fos expression in the medial prefrontal cortex(mPFC) of adult male mice. Transcriptome sequencing was performed to determine the effect of lithium administration on the transcriptome of the PFC in ketamine-treated mice, showing inactivation of the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Pharmacological inhibition of AKT signaling by MK2206(40 mg/kg), a selective AKT inhibitor, reversed ketamine-induced mania.Furthermore, selective knockdown of AKT via AAVAKT-sh RNA-EGFP in the mPFC also reversed ketamine-induced mania-like behavior. Importantly,pharmacological activation of AKT signaling by SC79(40 mg/kg), an AKT activator, contributed to mania in low-dose ketamine-treated mice. Inhibition of PI3K signaling by LY294002(25 mg/kg), a specific PI3K inhibitor, reversed the mania-like behavior in ketamine-treated mice. However, pharmacological inhibition of mammalian target of rapamycin(mTOR)signaling with rapamycin(10 mg/kg), a specific mTOR inhibitor, had no effect on ketamine-induced mania-like behavior. These results suggest that chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway, which may be a novel target for the development of BD treatment.

miR-199a-3p靶基因预测及生物信息学分析

目的为深入研究miR-199a-3p在膀胱癌形成和发展中的作用提供理论依据。方法分析miR-199a-3p序列,预测其靶基因和转录因子,并对靶基因进行GO富集和KEGG Pathway分析;构建TF-miR-199a-3p-靶基因网络调控图。结果 miR-199a-3p序列在多物种间具有高度保守性;GO分析发现miR-199a-3p的靶基因参与细胞调节、代谢调节、细胞大分子生物合成等生物过程(P<0.01);KEGG Pathway分析发现miR-199a-3p的靶基因显著富集在上皮细胞的细菌入侵通路、ECM受体的相互作用通路、PI3K-Akt信号通路、MAPK信号通路、小细胞肺癌通路、癌症中的蛋白聚糖通路等;根据构建的TF-miR-199a-3p-靶基因网络调控图,挖掘出可能受miR-199a-3p调控的重要基因有MYC、SP1、mTOR、NFκB、NFκB1等。结论 miR-199a-3p可能通过直接靶向作用mTOR,调节PI3K-Akt-mTOR信号通路,从而参与膀胱癌的形成和发展。

Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of Gualou Qumai Wan in clear cell renal cell carcinoma

Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.

Regulatory effects of antitumor agent matrine on FOXO and PI3K-AKT pathway in castration-resistant prostate cancer cells

We previously demonstrated that matrine could inhibit the proliferating, migrating, as well as invading processes of both PC-3 and DU145 cells. However, the underlying molecular mechanisms have not yet been clearly defined. In this study, using various techniques such as high throughput sequencing technology, bioinformatics, quantitative real-time PCR, and immunoblot analysis,we aimed to understand whether matrine serves as a novel regulator of FOXO and PI3K-AKT signaling pathway. DU145 and PC-3 cell lines were cultured for 24 h in vitro. Cells were treated with either matrine or control serum for 48 h, followed by extraction of total RNA. The RNA was sequenced using HiSeq 2500 high-throughput sequencing platform (Illumina). A gene library was established and quality analysis of read data carried out. Integrated database from the website DAVID was used to analyze Gene Ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway of differential genes was used for pathway analysis, screening for fold differences of more than two times. The FOXO and PI3K-AKT signaling pathways were screened, and expression levels of mRNA and core protein detected by real-time PCR and immunoblotting, respectively. High throughput sequencing and GO analysis revealed that differentially expressed genes before and after treatment played an important role in cell metabolic process, growth process, anatomical structure formation, cellular component organization, and biological regulation. KEGG signal pathway analysis revealed that FOXO and PI3K-AKT signal pathways had a significant difference between before and after matrine-treated androgen-independent prostate cancer cells PC-3 and DU145. Real-time PCR showed that matrine treatment led to a significant increase in the expression levels of FOXO1A, FOXO3A, FOXO4, and FOXO6 in DU145 and PC-3 cells (P<0.01 or P<0.05), whereas the PI3K expression levels decreased (P<0.01). Similarly, immunoblotting revealed a significant increase (P<0.05) in the expression levels of FOXO1A FOXO3A, FOXO4, and FOXO6 in both PC-3 and DU145 cells, whereas PI3K expression levels decreased (P<0.05). Matrine had a broad regulating effect on the mRNA expression profiles of both PC-3 and DU145 cells. Matrine may inhibit cell proliferation, migration, as well as invasion, and induce apoptosis in both PC-3 and DU145 cells through FOXO and PI3K-AKT signaling pathways. Matrine could therefore be used as a complementary drug to present chemotherapeutic agents, for treating androgen-independent prostate cancer.

Modulation of mitochondrial respiration underpins neuronal differentiation enhanced by lutein

Lutein is a dietary carotenoid of particular nutritional interest as it is preferentially taken up by neural tissues. Often linked with beneficial effects on vision, a broader role for lutein in neuronal differentiation has emerged recently, although the underlying mechanisms for these effects are not yet dear. The purpose of this study was to investigate the effect of lutein on neuronal differentiation and explore the associated underpinning mechanisms. We found that lutein treatment enhanced the differentiation of SH-SYSY cells, specifically increasing neuronal arborization and expression of the neuronal process filament protein microtubule-associated protein 2. This effect was mediated by the intracellular phosphoinositide-3-kinase （PI3K） signaling pathway. While PI3K activity is a known trigger of neuronal differentiation, more recently it has also been shown to modulate the metabolic state of cells. Our analysis of bioenergetics found that lutein treatment increased glucose consumption, rates of glycolysis and enhanced respiratory activity of mitochondrial complexes. Concomitantly, the generation of reactive oxygen species was increased （con- sistent with previous reports that reactive oxygen species promote neuronal differentiation）, as well as the production of the key metabolic intermediate acetyl-CoA, an essential determinant of epigenetic status in the cell. We suggest that lutein-stimulated neuronal differentiation is mediated by PI3K-dependent modulation of mitochondrial respiration and signaling, and that the consequential metabolic shifts initiate epigenetically dependent transcriptomic reprogramming in support of this morphogenesis. These obser- vations support the potential importance of micronutrients supplementation to neurogenesis, both during normal development and in regenerative repair.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Network pharmacology-based screening of the active ingredients and mechanisms of Cymbaria daurica against diabetes mellitus

Cymbaria daurica L.has a long history as a folk medicine and tea for the treatment of diabetes.However,the biological activity and mechanism of its hypoglycemic effect have not been fully elucidated.In this study,the potential mechanism of C.daurica against type 2 diabetes mellitus(T2DM)was postulated via pharmacological network analysis.Based on data mining techniques involving topological parameters,gene ontology,and pathway enrichment,we established a compound-target,protein-protein interaction,and target-pathway network to identify central targets and pathways.Pathway enrichment analysis revealed that the most important pathway associated with C.daurica in treating T2DM is the PI3K-Akt signaling pathway.Molecular docking was performed to validate the predicted results.Then,a HepG2 cell insulin resistance model and a high-fat,high-glucose diet combined with a streptozotocin-induced T2DM rat model was established to assess the fasting glucose changes and lipid profile after C.daurica treatment,respectively.Finally,real-time PCR and western blotting were used to verify changes in key targets.The anti-diabetic mechanism of the active ingredient in C.daurica may involve the regulation of IRS-2,Akt1,GLUT4,and GSK3β.

The extracellular secretion of miR-1825 wrapped by exosomes increases CLEC5A expression:A potential oncogenic mechanism in ovarian cancer

Background:Ovarian cancer(OC)is a leading cause of gynecological cancer-linked deaths worldwide.Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A(CLEC5A)are associated with tumorigenesis in cancers that was further probed.Methods:Exosomal miR-1825 expression in exosomes and its impact on overall survival(OS)prediction were determined using Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)data.Target genes of miR-1825 were searched in five prediction databases and prognostically significant differentially expressed genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were carried out.The ability of CLEC5A to predict OS was evaluated using univariate and multivariate Cox regression analyses and Kaplan-Meier curves.The CLEC5A expression pattern in OC was validated using immunohistochemistry.The CIBERSORT algorithm was used to compare the immune cell landscape,and the results were validated in a GEO cohort.Finally,the predicted half maximal inhibitory concentration(IC50)values for five commonly used chemotherapy agents were also compared.Results:MiR-1825 level was higher in exosomes derived from OC cells and served as a tumor suppressor.The CLEC5A gene was found to be a target of miR-1825,the upregulation of which was correlated with a poor prognosis.M2 macrophage infiltration was significantly enhanced in the CLEC5A high expression group,while T follicular helper cell infiltration was reduced in it.While the predicted IC50 for cisplatin and doxorubicin was higher in the CLEC5A high expression group,that of docetaxel,gemcitabine,and paclitaxel was lower.Conclusion:MiR-1825,a promising OC biomarker,may promote OC progression by increasing CLEC5A expression via exosome-mediated efflux from tumor cells.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Akt信号通路与细胞存活的研究进展

Akt/PKB是一种丝/苏氨酸蛋白激酶,由三个高度同源的Akt1、Akt2和Akt3组成。在对Akt/PKB的上游机制中不断了解的同时,我们也认识到Akt的下游途径与协调信号的特异性有关,通过影响下游多种效应分子的活化状态,发挥着调节细胞存活、代谢、增殖的作用。Akt/PKB信号通路在与肿瘤、心血管疾病、神经系统疾病的发生发展密切相关而受到重视。本文主要对Akt/PKB信号通路的组成与功能,调节及抗凋亡方面的研究进展作一综述,期待为以Akt/PKB为作用靶点的治疗研究提供参考。

脊髓缺血再灌注损伤相关信号通路研究进展

目前对SCII的发生、发展及转归已取得较为深入的研究,但其细胞信号转导机制尚不明确。研究表明,多条细胞信号通路参与了SCII的病理生理过程,其中核因子-κB(NF-κB)、分裂原激活蛋白激酶(MAPK)、PI3K-Akt/PKB、JAK-STAT、蛋白激酶C(PKC)在SCII中发挥着重要作用,各信号通路之间也存在交互对话,相互调控。

Study on the Mechanism of Angelica sinensis-Phellodendri Chinensis Cortex in the Treatment of Chronic Prostatitis Based on Network Pharmacology

[Objectives]To explore the mechanism of Angelica sinensis-Phellodendri Chinensis Cortex in the treatment of chronic prostatitis(CP)based on the method of network pharmacology.[Methods]The active components and action targets of Angelica sinensis-Phellodendri Chinensis Cortex were screened by(TCMSP),a systematic pharmacological analysis platform of traditional Chinese medicine,combined with literature search.The target was corrected by Uniprot database,and the disease CP target was screened by GeneCards and OMIM database.The common targets of drugs and diseases were screened by R language software,and the visual network map of drugs-active components-targets-diseases was constructed by Cytoscape 3.5.1 software.The common target protein-protein interaction(PPI)network was constructed by using STRING platform.The R language software was used to annotate and analyze the gene function and pathway of the core target through geneontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).[Results]46 active components of Angelica sinensis-Phellodendri Chinensis Cortex were screened,and 212 related targets were predicted,of which 159 were related to disease.These targets were mainly involved in biological processes such as heterologous biological stimulation,oxidation and anti-oxidation,and were mainly concentrated in PI3K-Akt,mitogen-activated protein kinase(MAPK),hypoxia inducible factor-1(HIF-1)and other related signaling pathways.[Conclusions]The multi-component,multi-target and multi-pathway action characteristics of Angelica sinensis-Phellodendri Chinensis Cortex were confirmed by network pharmacology,and the possible mechanism of Angelica sinensis-Phellodendri Chinensis Cortex in the treatment of CP was predicted,which provided a theoretical basis for further experiments to verify its action mechanism.

The mechanism of Astragalus membranaceus in treating peritoneal fibrosis by intervening the key syndrome and pathology based on Q-marker theory

Objective:To evaluate the mechanism of Astragalus membranaceus(AM)by intervening peritoneal mesothelial cells(PMCs),epithelial-mesenchymal transition(EMT),and spleen deficiency syndrome(SDS)in peritoneal fibrosis(PF),we base on employing the strategy of Q-marker theory combination network pharmacology method.Methods:First,we obtained the Q-markers of AM by searching the relevant literature and its pharmacological information was collected based on SwissADME.The SwissTargetPrediction and pharmmaper were employed to predict its potential target.Secondly,GeneCards,DisGeNET,and OMIM databases were employed to search the related targets of EMT,SDS,and PF.VENNY2.1 tool was employed to obtain the intersection targets of AM and the three;then the“AM potential target-SDS-EMT-PF”Venn diagram was constructed.The common targets of AM,EMT and SDS were uploaded to the STRING database and obtained the PPI protein interaction network map.Cytoscape 3.7.2 was employed to evaluate the core target of PPI network.PATHER and Metascape databases were used to analyze protein type,GO biological process,and KEGG pathway.Finally,a network diagram of the“TCM-component-disease target-pathway”was drawn.Results:A total of 10 AM Q-makers were screened out,corresponding to 335 targets of AM,2,728 targets of SDS,373 of EMT,and 612 PF targets were found.Among them,there are 155 common AM targets related to SDS and EMT.Key targets such as ALB,AKT1,VEGFA,TNF,EGFR,CASP3,SRC,STAT3,HSP90AA1,and ESR1 were obtained.The core drug include quercetin,astragalosideIII,Calycosin-7-O-beta-D-glucoside,astragalosideIV,etc.The types of PPI proteins include protein modification enzymes,metabolite transferases,transmembrane signal receptors,etc.Biological processes include the regulation of kinase activity,the positive regulation of transferase activity,and the regulation of kinase activity.The key pathways may include PI3K-Akt signaling pathways,the non-smad pathway of the TGF-βsignaling pathway,and the AGE-RAGE signaling pathway.Conclusion:AM could prevent and treat PF through a multi-component multi-target-multi-path mechanism.Astragalus saponins may be the main component types of AM intervening EMT pathology by strengthening the spleen and nourishing Qi.AstragalosideIV and astragalosideIII may be the constituents that can invigorate the spleen and replenish Qi.The results of this study contribute to a more comprehensive understanding of the critical components and mechanisms of AM by intervening SDS and EMT in the treatment of PF.

Hypoglycemic effect of Moringa oleifera leaf extract and its mechanism prediction based on network pharmacology

Diabetes mellitus(DM)is a chronic metabolic disease characterized by hyperglycemia,which poses a serious threat to human health.Moringa oleifera Lam.is a medicinal and edible plant with various physiological functions.However,its main hypoglycemic components and mechanisms are still unclear.In this study,network pharmacology and bioinformatics were used to analyze the potential bioactive substances of M.oleifera leaf extract(MOLE)and its hypoglycemic mechanism.Studies have shown that MOLE has the effect of increasing glucose consumption in insulin resistant-HepG2 cells.MOLE was found to contain 975 compounds by ultrahigh performance liquid chromatography-mass spectrometry(UHPLC-MS).Network pharmacology analysis indicated that the main active component was robinetin and the identified core genes were AKT1 and GAPDH.KEGG pathway enrichment analysis showed that the hypoglycemic effect of MOLE may be closely related to the PI3K-Akt signaling pathway.This study revealed the possible active components and mechanisms of action of M.oleifera for hypoglycemia,laying the theoretical foundation for subsequent studies.