Chemical constituents and synergistic anti-gout studies on Eurycoma longifolia and potential mechanisms evaluation based on systemic analysis approach

37 compounds mainly including triterpenoids with the quassinoid skeleton and β-carboline alkaloids have been isolated from the roots of Eurycoma longifolia Jack (EL), which has been used as traditional medicine for a long history. It has been demonstrated that the total extracts from EL could significantly inhibit the joint swelling in MSU-induced acute gout arthritis rat model at middle and high doses (P < 0.05, P < 0.01), as meanwhile, better performance than that of positive control (P < 0.05, P < 0.01) has been observed at the dose of 10 g/kg. Aiming to search potential compounds and probable mechanisms, network pharmacology, molecular docking and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were adopted, leading to the hypothesis of 17 targets related to different pathogenesis of gout and 5 potential compounds (C36, C107, C124, C125 and C130) among 156 selected compounds, playing synergetic role with multiple targets. Instead of the guiding ideology of “a gene, a drug, a disease”, varieties of compounds but not a single one from EL display holistic performance through multiple pathways with multi-targets. It was noteworthy that Xanthine dehydrogenase/oxidase (XDH), Prostaglandin G/H synthase 2 (PTGS2), Fatty acid-binding protein, liver (FABP1), Purine nucleoside phosphorylase (PNP), and Peroxisome proliferator activated receptor alpha (PPARA) were the key targets with intensely interaction. Furthermore, the functional enrichment analysis indicated that EL probably produced the gout protection effects by synergistic regulation in multiple biological pathways, including Toll-like receptor signaling pathway, MAPK signaling pathway, and NOD-like receptor signaling pathway, etc.     

Virtual screening of active compounds from Artemisia argyi and potential targets against gastric ulcer based on Network pharmacology

Artemisia argyi (AA) is one of the renowned herbs in China often used in the treatment of gastric ulcer (GU). Aiming to predict the active compounds and systematically investigate the mechanisms of Artemisia argyi for GU treatment, the approach of network pharmacology, molecular docking, gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were adopted, respectively, in present study. A total of 13 predicted targets of the 103 compounds in Artemisia argyi were obtained. Sorted by pathogenic mechanisms of targets and structure types of compounds, it was revealed that flavonoids and sesquiterpenes had better performance than monoterpenes. The network analysis showed that Phospholipase a2 (PA21B), Sulfotransferase family cytosolic 2b member 1 (ST2B1), Nitric-oxide synthase, endothelial (NOS3), Gastrin (GAST), neutrophil collagenase (MMP-8), Leukotriene A-4 hydrolase (LKHA4), Urease maturation factor HypB (HYPB), and Periplasmic serine endoprotease DegP (HtrA) were the key targets with intensely interaction. The functional enrichment analysis indicated that AA probably produced the gastric mucosa protection effects by synergistically regulating many biological pathways, such as NF-κB signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, VEGF signaling pathway, and Toll-like receptor signaling pathway, etc. In addition, C73 and C15 might be promising leading compounds with good molecular docking score. As a consequence, this study holistically illuminates the active constituents and mechanisms based on data analysis, which contributes to searching for leading compounds and the development of new drugs for gastric ulcer.     

基于网络药理学和分子对接探索桑白皮治疗糖尿病周围神经病变的潜在机制

本研究运用网络药理学和分子对接方法对中药桑白皮治疗糖尿病周围神经病变(DPN)的活性成分、潜在作用靶点和信号通路进行研究,探索桑白皮治疗DPN的可能作用机制。首先从中药系统药理学数据库(TCMSP)筛选出桑白皮的活性成分及靶点基因。通过GeneCards数据库及OMIM数据库筛选出DPN的疾病靶点基因,并用Cytoscape软件构建"药物-有效成分-靶基因-疾病"中药调控网络图。将有效成分靶标与疾病靶标上传到STRING数据库,构建蛋白互作网络图(PPI),并使用R语言对得到的PPI进行核心基因的筛选。运用R语言对关键靶点进行GO富集分析和KEGG通路富集分析。其次从活性成分及靶点基因中根据degree值筛选出前3个关键成分,并将该网络中的基因靶点以degree值高低进行排序,选择前3个核心靶点,然后从RCSB数据库下载相关蛋白的结构,使用Pymol软件去除溶剂分子与配体,使用AutoDock软件进行分子对接。最后通过酶联免疫吸附实验和荧光光谱实验验证网络药理学富集分析的结果。最终预测到31个桑白皮活性成分,312个活性成分相关靶点,120个桑白皮-糖尿病周围神经病变共同有效靶点。活性...     

基于网络药理学-分子对接研究桑不同入药部位防治糖尿病的作用机制

采用网络药理学-分子对接研究桑不同入药部位防治糖尿病的作用机制,从TCMSP、TCMID等多个中药数据库获得桑不同部位桑叶、桑椹、桑枝中的成分信息,结合OMIM、TTD等疾病数据库获得糖尿病靶点信息,利用Cyto-scape 3.7.2软件分别构建不同部位的“活性成分-疾病靶点”的复杂网络及拓扑分析,应用WebGest...     

基于网络药理学与分子对接技术的清瘟护肺颗粒防治新型冠状病毒肺炎(COVID-19)的潜在药效物质研究

本文通过网络药理学和分子对接技术探讨清瘟护肺颗粒防治新型冠状病毒肺炎(COVID-19)的潜在药效物质.首先,通过TCMSP数据库,BATMAN-TCM数据库及TCMIP数据库检索清瘟护肺颗粒中十六味药的化学成分及作用靶点,利用GeneCards和OMIM数据库检索COVID-19的相关疾病靶点.然后,通过venny2...     

Exploration of the molecular targets and mechanisms of suxiao xintong dropping pills for myocardial infarction by network pharmacology method

Background: Suxiao Xintong dropping pills (SXXTDP), a traditional Chinese medicine, is widely applied for treating myocardial infarction (MI). However, its therapy mechanisms are still unclear. Therefore, this research is designed to explore the molecular mechanisms of SXXTDP in treating MI.Methods: The active ingredients of SXXTDP and their corresponding genes of the active ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. MI-related genes were identified via analyzing the expression profiling data (accession number: {"type":"entrez-geo","attrs":{"text":"GSE97320","term_id":"97320"}}GSE97320). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to study the shared genes of drug and disease. Through protein–protein interaction (PPI) network and the Cytoscape plugin cytoHubba, the hub genes were screened out. The compounds and hub targets binding were simulated through molecular docking method.Results: We obtained 21 active compounds and 253 corresponding target genes from TCMSP database. 1833 MI-related genes were identified according to P<0.05 and |log₂FC| ≥ 0.5. 27 overlapping genes between drug and disease were acquired. GO analysis indicated that overlapping genes were mainly enriched in MAP kinase activity and antioxidant activity. KEGG analysis indicated that overlapping genes were mainly enriched in IL-17 signaling pathway and TNF signaling pathway. We obtained 10 hub genes via cytoHubba plugin. Six of the 10 hub genes, including PTGS2, MAPK14, MMP9, MAPK1, NFKBIA, and CASP8, were acted on molecular docking verification with their corresponding compounds of SXXTDP.Conclusion: SXXTDP may exert cardioprotection effect through regulating multiple targets and multiple pathways in MI.     

Active Ingredients and Anti‐Arthritic Mechanisms of Ba‐Wei‐Long‐Zuan Granule Revealed by 1H‐NMR‐Based Metabolomics Combined with Network Pharmacology Analysis

Ba‐Wei‐Long‐Zuan granule (BWLZ) is a traditional herbal preparation. It has been widely used for the treatment of rheumatoid arthritis (RA). However, its active ingredients and mechanisms of action are still unclear. The present study aims to reveal the active compounds and anti‐arthritic mechanisms of BWLZ against collagen‐induced arthritis (CIA) by using ¹H‐NMR‐based metabolomics, molecular docking and network pharmacology methods. After 30 days of administration, BWLZ could effectively improve the metabolic disorders in CIA rats. The anti‐arthritic effect of BWLZ was related to its restoration of 16 disturbed serum metabolites. Molecular docking and network analysis showed that 20 compounds present in BWLZ could act on multiple targets. Among them, coclaurine and hesperidin showed the highest hit rates for target proteins related to both metabolic regulation and RA, indicating that these two compounds might be potential active ingredients of BWLZ. Moreover, pathway enrichment analysis suggested that the anti‐arthritic mechanisms of BWLZ might be attributed to its network regulation of several biological processes, such as steroid hormone biosynthesis, mTOR signaling pathway, alanine, aspartate and glutamate metabolism, and synthesis and degradation of ketone bodies. These results provide further evidence for the anti‐arthritic properties of BWLZ and are beneficial for its quality control and clinical application. The potential targets and biological processes found in this study may provide valuable information for further studying the molecular mechanisms of BWLZ against RA. In addition, our work provides new insights for revealing the active ingredients and regulatory mechanisms of complex herbal preparations.     

基于网络药理学和分子对接探讨银杏叶治疗高血压病潜在作用机制

通过网络药理学和分子对接技术探讨银杏叶治疗高血压的潜在作用机制.首先,通过TCMSP、Swiss Target Prediction、Uniprot等数据库获取银杏叶的化学成分与对应靶点;运用OMIM、DrugBank及Gencards疾病数据库搜索高血压相关靶点.然后,取银杏叶对应靶点与高血压相关靶点的交集即可得到银...     

基于网络药理学探讨丹参-丹皮配伍抗脑缺血损伤的作用机制

本文旨在通过网络药理学和分子对接方法探讨丹参-丹皮活性成分治疗脑卒中的潜在分子机制.首先基于中药系统药理学分析平台筛选丹参、丹皮的活性成分及其作用靶点,利用CTD、TTD和GeneCards数据库收集脑卒中相关靶点.然后将药物和疾病靶点取交集,借助STRING数据库获取靶点间相互作用关系,利用R语言的Cluster-P...     

Effect of dapagliflozin on diabetic patients with cardiovascular disease via MAPK signalling pathway

Clinical studies have shown that dapagliflozin can reduce cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM), but the exact mechanism is unclear. In this study, we used the molecular docking and network pharmacology methods to explore the potential mechanism of dapagliflozin on T2DM complicated with cardiovascular diseases (CVD). Dapagliflozin's potential targets were predicted via the Swiss Target Prediction platform. The pathogenic targets of T2DM and CVD were screened by the Online Mendelian Inheritance in Man (OMIM) and Gene Cards databases. The common targets of dapagliflozin, T2DM and CVD were used to establish a protein-protein interaction (PPI) network; the potential protein functional modules in the PPI network were found out by MCODE. Metascape tool was used for Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis. A potential protein functional module with the best score was obtained from the PPI network and 9 targets in the protein functional module all showed good binding properties when docking with dapagliflozin. The results of KEGG pathway enrichment analysis showed that the underlying mechanism mainly involved AGE-RAGE signalling pathway in diabetic complications, TNF signalling pathway and MAPK signalling pathway. Significantly, the MAPK signalling pathway was considered as the key pathway. In conclusion, we speculated that dapagliflozin played a therapeutic role in T2DM complicated with CVD mainly through MAPK signalling pathway. This study preliminarily reveals the possible mechanism of dapagliflozin in the treatment of T2DM complicated with CVD and provides a theoretical basis for future clinical research.     

Network pharmacology,molecular docking integrated surface plasmon resonance technology reveals the mechanism of Toujie Quwen Granules against coronavirus disease 2019 pneumonia

BackgroundThe Coronavirus disease 2019 pneumonia broke out in 2019 (COVID-19) and spread rapidly, which causes serious harm to the health of people and a huge economic burden around the world.PurposeIn this study, the network pharmacology, molecular docking and surface plasmon resonance technology (SPR) were used to explore the potential compounds and interaction mechanism in the Toujie Quwen Granules (TQG) for the treatment of coronavirus pneumonia 2019.Study designThe chemical constituents and compound targets of Lonicerae Japonicae Flos, Pseudostellariae Radix, Artemisia Annua L, Peucedani Radix, Forsythiae Fructus, Scutellariae Radix, Hedysarum Multijugum Maxim, Isatidis Folium, Radix Bupleuri, Fritiliariae Irrhosae Bulbus, Cicadae Periostracum, Poria Cocos Wolf, Pseudobulbus Cremastrae Seu Pleiones, Mume Fructus, Figwort Root and Fritillariae Thunbrgii Bulbus in TQG were searched. The target name was translated to gene name using the UniProt database and then the Chinese medicine-compound-target network was constructed. Protein-protein interaction network (PPI), Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the core targets were performed in the Metascape to predict its mechanism. The top 34 compounds in the Chinese medicine-compound-target network were docked with SARS-CoV-2 3CL enzyme and SARS-­CoV­-2 RNA-dependent RNA polymerase (RdRp) and then the 13 compounds with lowest affinity score were docked with angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 Spike protein and interleukin 6 to explore its interaction mechanism. Lastly, SPR experiments were done using the quercetin, astragaloside IV, rutin and isoquercitrin, which were screened from the Chinese medicine-compound-target network and molecular docking.ResultsThe Chinese medicine-compound-target network includes 16 medicinal materials, 111 compounds and 298 targets, in which the degree of PTGS2, TNF and IL­6 is higher compared with other targets and which are the disease target exactly. The result of GO function enrichment analysis included the response to the molecule of bacterial origin, positive regulation of cell death, apoptotic signaling pathway, cytokine-mediated signaling pathway, cytokine receptor binding and so on. KEGG pathway analysis enrichment revealed two pathways: signaling pathway­ IL-17 and signaling pathway­ TNF. The result of molecular docking showed that the affinity score of compounds including quercetin, isoquercitrin, astragaloside IV and rutin is higher than other compounds. In addition, the SPR experiments revealed that the quercetin and isoquercitrin were combined with SARS-CoV-2 Spike protein rather than Angiotensin-converting enzyme 2, while astragaloside IV and rutin were combined with ACE2 rather than SARS-CoV-2 Spike protein.ConclusionTQG may have therapeutic effects on COVID-19 by regulating viral infection, immune and inflammation related targets and pathways, in the way of multi-component, multi-target and multi-pathway.     

Exploring the mechanism of ellagic acid against gastric cancer based on bioinformatics analysis and network pharmacology

Ellagic acid (EA) is a natural polyphenolic compound. Recent studies have shown that EA has potential anticancer properties against gastric cancer (GC). This study aims to reveal the potential targets and mechanisms of EA against GC. This study adopted methods of bioinformatics analysis and network pharmacology, including the weighted gene co-expression network analysis (WGCNA), construction of protein–protein interaction (PPI) network, receiver operating characteristic (ROC) and Kaplan–Meier (KM) survival curve analysis, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, molecular docking and molecular dynamics simulations (MDS). A total of 540 EA targets were obtained. Through WGCNA, we obtained a total of 2914 GC clinical module genes, combined with the disease database for screening, a total of 606 GC-related targets and 79 intersection targets of EA and GC were obtained by constructing Venn diagram. PPI network was constructed to identify 14 core candidate targets; TP53, JUN, CASP3, HSP90AA1, VEGFA, HRAS, CDH1, MAPK3, CDKN1A, SRC, CYCS, BCL2L1 and CDK4 were identified as the key targets of EA regulation of GC by ROC and KM curve analysis. The enrichment analysis of GO and KEGG pathways of key targets was performed, and they were mainly enriched in p53 signalling pathway, PI3K-Akt signalling pathway. The results of molecular docking and MDS showed that EA could effectively bind to 13 key targets to form stable protein–ligand complexes. This study revealed the key targets and molecular mechanisms of EA against GC and provided a theoretical basis for further study of the pharmacological mechanism of EA against GC.     

基于网络药理学的益母草治疗产后腹痛的潜在分子机制研究

本文通过网络药理学方法探讨益母草治疗产后腹痛的潜在分子机制。首先根据TCMSP数据库和文献挖掘益母草的活性成分,在TCMSP、Swiss Target Prediction、Similarity ensemble approach平台上检索活性成分靶点,在OMIM、GeneCards上检索产后腹痛靶点,得到益母草-产后腹痛交集靶点。利用STRING数据库构建蛋白互作(PPI)网络,接着利用Cytoscape软件对PPI网络进行拓扑分析,并对拓扑分析筛选出的核心靶点进行基因本体论(Gene Ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。最后利用免疫组化实验验证益母草对流产大鼠模型子宫组织中PGF2αR、MMP9、TIMP1、VEGFA、VEGFR2蛋白表达水平的影响。最终得到益母草活性成分10种,与产后腹痛相关靶点144个;通过PPI网络分析筛选出118个靶点,进一步拓扑分析后得到98个节点;然后对这98个节点进行GO和KEGG注释。GO分析得到1151个生物过程(BP)条目,97个细胞组成(CC)条目,122个分子功能(MF)条目;KEGG分析得到41条通路,主要涉及雌激素、PI3K-Akt、MAPK、HIF-1信号通路等。最后免疫组化实验证明益母草可显著抑制流产模型大鼠子宫组织中PGF2αR、MMP9蛋白上调和TIMP1、VEGFR2蛋白下调。本研究通过网络药理学和免疫组化实验验证,显示益母草治疗产后腹痛是多成分、多靶点、多途径相互作用的结果,为益母草的临床应用提供了一定的理论依据。     

网络药理学和分子对接技术研究桑黄类真菌对疾病的潜在作用机制

桑黄类真菌是一类极具研究价值的药用真菌。近年来,对于桑黄类真菌的研究,多集中于对某一个物种的成分及药理活性的研究,系统比较桑黄类真菌中成分及药理活性的研究较少。本研究利用网络药理学和分子对接技术从理论上初步探讨了5种桑黄类真菌中化合物与疾病之间的分子作用机制。研究结果表明5种桑黄类真菌(栎木桑黄Sanghuangporus quercicola、鲍姆桑黄Sanghuangporus baumii、粗毛纤孔菌Inonotus hispidus、裂蹄木层孔菌Tropicorus linteus、黑盖木层孔菌Phellinus nigrians)中的39种有效成分,对应潜在靶点588个。KEGG通路富集筛选得到165条通路,分析结果发现这39种化合物的靶点主要分布在与炎症、糖尿病、肝癌、阿尔茨海默病和衰老相关的信号通路上。筛选出桑黄类真菌中抗病的潜在靶点共486个,构建抗病靶点的蛋白互作(PPI)网络,并筛选出LCK、STAT3、PTPN11、STAT1、STAT5B、MAPK1、JAK1、MAPK3、JAK3和JAK2作为关键靶点,构建5种桑黄类真菌-化合物-关键靶点-5种疾病的网络互作图,并进行分子对接验证。筛选出的桑黄类真菌中的12个有效成分均可与这些关键靶点产生相互作用,其中酚类化合物居多,此外二萜类化合物异海松酸与MAPK1结合能力最强。因此,5种桑黄类真菌可以通过多种化合物、多种靶点和多种途径起到抗病的作用,本研究为探索桑黄类真菌治疗和预防疾病潜在机制提供了理论基础。     

基于网络药理学、分子对接和实验验证探讨朱茯苓用于失眠的作用机制

为探讨朱茯苓治疗失眠的可能作用机制,通过TCMSP、BAT-MAN、TCMID和STITCH数据库以及文献挖掘筛选朱茯苓的活性成分及潜在靶点,利用TTD、OMIM、GeneCards和CTD数据库获取失眠类疾病的相关靶点,采用Cyto-scape软件和String数据库构建活性成分-靶点网络和靶点蛋白相互作用网络,通过...     

Effect of contraction on mitogen-activated protein kinase signal transduction in skeletal muscle. Involvement Of the mitogen- and stress-activated protein kinase 1

Growing evidence suggests that activation of mitogen-activated protein kinase (MAPK) signal transduction mediates changes in muscle gene expression in response to exercise. Nevertheless, little is known about upstream or downstream regulation of MAPK in response to muscle contraction. Here we show that ex vivo muscle contraction stimulates extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p38(MAPK) phosphorylation. Phosphorylation of ERK1/2 or p38(MAPK) was unaffected by protein kinase C inhibition (GF109203X), suggesting that protein kinase C is not involved in mediating contraction-induced MAPK signaling. Contraction-stimulated phosphorylation of ERK1/2 and p38(MAPK) was completely inhibited by pretreatment with PD98059 (MAPK kinase inhibitor) and SB203580 (p38(MAPK) inhibitor), respectively. Muscle contraction also activated MAPK downstream targets p90 ribosomal S6 kinase (p90(Rsk)), MAPK-activated protein kinase 2 (MAPKAP-K2), and mitogen- and stress-activated protein kinase 1 (MSK1). Use of PD98059 or SB203580 revealed that stimulation of p90(Rsk) and MAPKAP-K2 most closely reflects ERK and p38(MAPK) stimulation, respectively. Stimulation of MSK1 in contracting skeletal muscle required the activation of both ERK and p38(MAPK). These data demonstrate that muscle contraction, separate from systemic influence, activates MAPK signaling. Furthermore, we are the first to show that contractile activity stimulates MAPKAP-K2 and MSK1.     

基于HPLC-Q-TOF-MS/MS技术的蒲公英化学成分分析及其抗癌机制的网络药理学研究

为了探究蒲公英主要成分,分析其抗癌的可能机制及作用靶点,借助HPLC-Q-TOF-MS/MS技术对蒲公英提取物进行分析,利用SwissADME、Swiss Target Prediction和GeneCards数据库获取蒲公英主要活性成分和抗癌的作用靶点,通过String在线数据库构建靶蛋白相互作用网络,并利用DVIAD在线数据库对关键靶点进行GO和KEGG富集分析。最终从蒲公英提取物中共鉴定出29个化合物,主要包括有机酸类、黄酮类等化学成分,筛选到10个活性成分,成分-疾病的共同靶点84个。网络分析显示,主要活性成分为槲皮素、木犀草素、芹菜素等,关键靶点为AKT1、EGFR、SRC、ESR1、PTGS2、MMP9、KDR、MMP2、PIK3R1,并且涉及氧化-还原、负调控凋亡、蛋白质自磷酸化、ATP结合、蛋白激酶活性、蛋白丝氨酸/苏氨酸激酶活性、酶结合等过程,和癌症通路、癌症蛋白聚糖、PI3K-Akt信号通路等通路。综上,蒲公英是通过多成分、多靶点、多途径来发挥抗癌作用的。     

Revealing mechanism of Caulis Sargentodoxae for the treatment of ulcerative colitis based on network pharmacology approach

Objective: The traditional Chinese medicine Caulis Sargentodoxae is widely used in the treatment of ulcerative colitis (UC), but the mechanism remains unknown. The present study aims to reveal its effective components, targets and pathways through network pharmacology and bioinformatics approaches.Materials and methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to identify effective components. The ligand-based targets prediction was achieved through SwissTargetPrediction and TargetNet. UC-related targets were identified using Gene Expression Omnibus (GEO) data and DisGeNET. The common targets of disease and components were constructed and analyzed by PPI network. Lastly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are used to explain the functions of these common targets. Components-Targets-Pathways network was visualized and analyzed to further reveal the connection between the components and targets.Results: Eight active components and 102 key targets were identified to play an important role in UC. These targets were related to regulation of protein serine/threonine kinase activity, positive regulation of cell motility, response to molecule of bacterial origin, response to toxic substance, ERK1 and ERK2 cascade, peptidyl-tyrosine modification, inositol lipid-mediated signaling, cellular response to drug, regulation of inflammatory response and leukocyte migration. Moreover, HIF-1 signaling pathway and PI3K-Akt signaling pathway were the key targets involved in UC-related signaling pathways.Conclusion: The eight active components of Caulis Sargentodoxae mainly play a therapeutic role for UC through synergistic regulation of HIF-1 signaling pathway and PI3K-Akt signaling pathway.     

Combination of UHPLC-Q Exactive-Orbitrap MS,Bioinformatics and Molecular Docking to Reveal the Mechanism of Huan-Lian-Jie-Du Decoction in the Treatment of Diabetic Encephalopathy

Diabetic encephalopathy (DE) is a serious complication of diabetes, which affects patients′ quality of life. We aimed to explore HLJDD in the treatment of DE by LC/MS and bioinformatics. UPLC-Q Exactive-Orbitrap MS was employed to clarify the compounds. The modules and hub targets of DE were gained from WGCNA. Subsequently, an Herb-Compound-Target network was constructed and enrichment analysis was used. In addition, a protein-protein interaction (PPI) network was constructed and molecular docking was used to verify the above analysis. As result, 138 compounds and 10 prototypes in brain were identified. In network pharmacology, 8 modules and 5692 hub targets were obtained from WGCNA. An Herb-Compound-Target network was constructed by 4 herbs, 10 compounds and 56 targets. The enrichment analysis showed that the treatment of DE with HLJDD involve oxidative stress and neuroprotection. Beside, SRC, JUN, STAT3, MAPK1 and PIK3R1 were identified and as hub targets of HLJDD in treating DE. Moreover, Molecular docking showed that five hub targets had strong affinity with the corresponding alkaloids. Therefore, we explored the underlying mechanisms of HLJDD in the treatment of DE and to provide the theoretical and scientific basis for subsequent experimental studies and clinical applications.