Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Angelicae Pubescentis Radix in the treatment of rheumatoid arthritis

Abstract Purpose:To explore the potential target proteins underlying the effect of Angelicae Pubescentis Radix(APR) on rheumatoid arthritis (RA) using a network pharmacology and molecular docking approach .Methods:First, the active components and target proteins of APR and RA related disease targets were obtained from the TCMSP, Gene Card,OMIM,DisGeNET and STRING databases. Then the active ingredient target in the RA network diagram was drawn using Cytoscape 3.7.1 software. Protein-protein interaction analysis, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses were carried out using the STRING and David databases. The crystal structures of RA related targets were retrieved from the RCSB PDB database. Finally, the potential active compounds and their related targets were validated using molecular docking technology.Results: Five active components of Angelicae Pubescentis Radix(APR) were screened out, including ammidin, isoimperatorin, beta-sitosterol, O-acetylcolumbianetin and angelicone and 80 key targets including MAPK8,EGFR,PTGS2,CASPASE3,MTOR,SRC,KDR,MAPK1,NOS3 and MAPK14, etc were obtained. GO enrichment analysis showed that 222 biological processes, 34 cell components and 72 molecular functions were identified; KEGG analysis showed that the targets of APR in the treatment of RA were significantly enriched in pathways in cancer, the PI3K−Akt signaling pathway, Proteoglycans in cancer, osteoclast differentiation, neuroactive ligand−receptor interaction, tuberculosis,TNF signaling pathway, serotonergic synapse, Rap1 signaling pathway,cAMP signaling pathway. The results of molecular docking showed that ammidin, isoimperatorin, beta-sitosterol, O-acetylcolumbianetin and angelicone had strong affinity for PTGS2, EGFR and MAPK8.Conclusion: APR treats RA through the characteristics of multi-component, multi-target and multi-pathway regulation.

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Exploration of underlying molecular mechanism of Lycii Cortex in Treating Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

E3S Web of Conferences ◽

10.1051/e3sconf/202123302007 ◽

2021 ◽

Vol 233 ◽

pp. 02007

Author(s):

Dongjun Li ◽

Denghui Wang ◽

Shikai Yan

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Kegg Pathway Analysis ◽

Go Enrichment ◽

Core Components ◽

Receptor Signaling Pathway ◽

Go Enrichment Analysis

Objective: To explore the potential molecular mechanism of Lycii Cortex in treating type 2 diabetes mellitus (T2DM) by virtue of network pharmacology and molecular docking method. Methods: Ingredients of Lycii Cortex were collected from TCMSP and BATMAN-TCM databases, and the corresponding targets and T2DM-related targets were obtained respectively from SwissTargetPrediction and GenCards databases. Venn diagram was applied to derive the potential active components and effect targets of Lycii Cortex in the treatment of T2DM. GO enrichment analysis and KEGG pathway analysis were performed in the database of DAVID. Cytoscape 3.6.1 was used to produce the “core components-core targets” network. The molecular docking between core components and core targets was implemented through Autodock Vina. Results: Six core components and twelve core targets of Lycii Cortex in treating T2DM were identified. GO enrichment analysis and KEGG pathway analysis suggested the following signaling pathways and biological processes were involved in the treatment of T2DM by Lycii Cortex: PI3K-Akt signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and peptidyl-threonine phosphorylation, the positive regulation of cyclase activity, the positive regulation of genetic expression, and lipoprotein translocation. The binding results demonstrated a relatively high affinity between core components of Lycii Cortex, including kulactone, hederagenin, scopolin, etc., and core targets, containing IL6, PPARγ, TNF, and mTOR, indicating the efficacy of Lycii Cortex in treating T2DM. Conclusion: Lycii Cortex plays a role in the treatment of T2DM with its ingredients such as kulactone, linarin, hederagenin, and scopolin regulating glycometabolism, affecting cell apoptosis and weakening inflammatory response through targets like IL6, PPARγ, TNF, and mTOR.

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Network Pharmacology-based Strategy for Studying the Mechanism of Gegen Qinlian Decoction for the Treatment of Acute Colitis

10.21203/rs.3.rs-46831/v1 ◽

2020 ◽

Author(s):

Tingting Wang ◽

Yanwen Xu ◽

Wanli Ji ◽

Rui An

Keyword(s):

Signaling Pathway ◽

Biological Process ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Active Components ◽

Acute Colitis ◽

Rat Serum ◽

Kegg Pathway Analysis ◽

Go Enrichment ◽

Go Enrichment Analysis

Abstract Background: Gegen Qinlian Decoction(GQD) has been used to treat acute colitis (AC) for several years in China and it has shown good efficacy. However, the active components and target proteins of its anti-AC effects remains to be deciphered. Methods: In this study, serum pharmacochemistry and network pharmacology strategy were integrated to identify the constituents in blood and the mechanism of GQD for the treatment of AC. Ultra-performance liquid chromatography and LTQ-Orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS) was used to identify the absorbed components of GQD in rat serum; molecular docking and compound-target network analysis were used to predict candidate targets and critical components in GQD responsible for efficacy; In addition, the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis and Gene Ontology(GO) enrichment analysis were used to predict the related pathways and biological process respectively; Finally, the model rats with acute colitis were induced by DSS(Dextran Sulfact Sodium) in order to verify the effects and potential mechanism of baicalein, which is an important component of GQD. Results: Based on our comprehensive systematic approach, 23 components were successfully identified in rat serum after oral administration of GQD. The predicted results of molecular docking indicated that these 23 active components closely interacted with 41 protein targets associated with inflammation, immunity and enteric mucos. Among the 23 compounds identified, baicalin, baicalein, wogonoside , liquiritin and daidzin may be the most important components of GQD. Futhermore, according to GO enrichment analysis, the 41 candidate targets identified were mainly involved in two biological process, immune system process and inflammatory response. The KEGG pathway analysis revealed that 41 candidate targets were associated with 62 biological pathways, including HIF-1 signaling pathway and PI3K/Akt signaling pathway. Animal experiments found that baicalein could inhibit the activation of PI3K/Akt/HIF-1 signaling pathway and significantly reduce pro-inflammatory cytokines, such as IL-1β, IL-6, IL-8 and TNF-α to alleviate intestinal mucosal damage and achieve a therapeutic effect on AC. Conclusion: This research not only provides a novel and scientific strategy to better understand the complex mechanism of GQD, but also offers a new perspective to identify and/or discover novel active ingredients of TCM drugs.

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The Underlying Mechanism of Chinese Herb of Regulating Marrow in the Treatment of Osteonecrosis of the Femoral Head Based on Network Pharmacology and Molecular Docking

10.21203/rs.3.rs-699020/v1 ◽

2021 ◽

Author(s):

Xiaojian Wang ◽

Rui Wang ◽

Ting Xu ◽

Hongting Jin ◽

Peijian Tong ◽

...

Keyword(s):

Molecular Docking ◽

Chinese Medicine ◽

Signaling Pathway ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Underlying Mechanism ◽

Chinese Herbs ◽

Network Pharmacology ◽

Active Components ◽

Pathway Enrichment

Abstract Background The lesion of marrow is a crucial factor in orthopedic diseases, which is recognized by orthopedics-traumatology expert from "Zhe-School of Chinese Medicine". The Chinese herbs of regulating marrow has been widely used to treat osteonecrosis of the femoral head (ONFH) in China, while the interaction mechanisms were still elucidated. Thus, we conducted this study to explore the underlying mechanism of the five highest-frequency Chinese herbs of regulating marrow(HF-CHRM) in the treatment of ONFH with the aid of network pharmacology(NP) and molecular docking(MD). Methods The active components and potential targets of HF-CHRM were obtained through several online databases, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), UniProt database. The gene targets related to ONFH were collected with the help of the OMIM and GeneCards disease-related databases. The "drug- component-target-disease" network and protein-protein interaction(PPI) network of the drug and disease intersecting targets were constructed by using Cytoscape software and the STRING database. R software was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The MD of critical components and targets was carried out using Autodock Vina and Pymol to validate the binding affinity. Results A total of 54 active components, 1074 drug targets and 195 gene targets were obtained. There were 1219 ONFH related targets. 39 drug and disease intersection targets(representative genes: IL6, TP53, VEGFA, ESR1, IL1B) were obtained and considered potential therapeutic targets. 1619 items were obtained by the GO enrichment analysis, including 1517 biological processes, 10 cellular components and 92 molecular functions, which is mainly related to angiogenesis, bone and lipid metabolism and inflammatory reaction. The KEGG pathway enrichment analysis revealed 119 pathways, including AGE-RAGE signaling pathway, PI3K-Akt signaling pathway and IL-17 signaling pathway. MD results showed that quercetin, wogonin, and kaempferol active components had good affinity with IL6, TP53, and VEGFA core proteins. Conclusion The HF-CHRM can treat ONFH by multi-component, multi-target, and multi-pathway comprehensive action.

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Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/5786053 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Mengshi Tang ◽

Xi Xie ◽

Pengji Yi ◽

Jin Kang ◽

Jiafen Liao ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Docking ◽

Signaling Pathway ◽

Target Genes ◽

Enrichment Analysis ◽

Binding Activity ◽

New Combination ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Potential Mechanism

Objective. To explore the main components and unravel the potential mechanism of simiao pill (SM) on rheumatoid arthritis (RA) based on network pharmacological analysis and molecular docking. Methods. Related compounds were obtained from TCMSP and BATMAN-TCM database. Oral bioavailability and drug-likeness were then screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Additionally, target genes related to RA were acquired from GeneCards and OMIM database. Correlations about SM-RA, compounds-targets, and pathways-targets-compounds were visualized through Cytoscape 3.7.1. The protein-protein interaction (PPI) network was constructed by STRING. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via R packages. Molecular docking analysis was constructed by the Molecular Operating Environment (MOE). Results. A total of 72 potential compounds and 77 associated targets of SM were identified. The compounds-targets network analysis indicated that the 6 compounds, including quercetin, kaempferol, baicalein, wogonin, beta-sitosterol, and eugenol, were linked to ≥10 target genes, and the 10 target genes (PTGS1, ESR1, AR, PGR, CHRM3, PPARG, CHRM2, BCL2, CASP3, and RELA) were core target genes in the network. Enrichment analysis indicated that PI3K-Akt, TNF, and IL-17 signaling pathway may be a critical signaling pathway in the network pharmacology. Molecular docking showed that quercetin, kaempferol, baicalein, and wogonin have good binding activity with IL6, VEGFA, EGFR, and NFKBIA targets. Conclusion. The integrative investigation based on bioinformatics/network topology strategy may elaborate on the multicomponent synergy mechanisms of SM against RA and provide the way out to develop new combination medicines for RA.

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Study on the Mechanism of Acori Graminei Rhizoma in the Treatment of Alzheimer’s Disease Based on Network Pharmacology and Molecular Docking

BioMed Research International ◽

10.1155/2021/5418142 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yi Kuan Du ◽

Yue Xiao ◽

Shao Min Zhong ◽

Yi Xing Huang ◽

Qian Wen Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Signaling Pathway ◽

Target Prediction ◽

Enrichment Analysis ◽

The Elderly ◽

Estrogen Signaling ◽

Network Pharmacology ◽

Active Components

Alzheimer’s disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer’s disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of “drug-active ingredient-ingredient target.” A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer’s disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer’s signal pathway, thus reducing the production of Aβ, inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor.

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Exploring the Pharmacological Mechanism of Duhuo Jisheng Decoction in Treating Osteoporosis Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5510290 ◽

2021 ◽

Vol 2021 ◽

pp. 1-21

Author(s):

Zhencheng Xiong ◽

Can Zheng ◽

Yanan Chang ◽

Kuankuan Liu ◽

Li Shu ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Hub Genes ◽

Active Compounds ◽

Treatment Of Osteoporosis ◽

Target Proteins

Objective. The purpose of this work is to study the mechanism of action of Duhuo Jisheng Decoction (DHJSD) in the treatment of osteoporosis based on the methods of bioinformatics and network pharmacology. Methods. In this study, the active compounds of each medicinal ingredient of DHJSD and their corresponding targets were obtained from TCMSP database. Osteoporosis was treated as search query in GeneCards, MalaCards, DisGeNET, Therapeutic Target Database (TTD), Comparative Toxicogenomics Database (CTD), and OMIM databases to obtain disease-related genes. The overlapping targets of DHJSD and osteoporosis were identified, and then GO and KEGG enrichment analysis were performed. Cytoscape was employed to construct DHJSD-compounds-target genes-osteoporosis network and protein-protein interaction (PPI) network. CytoHubba was utilized to select the hub genes. The activities of binding of hub genes and key components were confirmed by molecular docking. Results. 174 active compounds and their 205 related potential targets were identified in DHJSD for the treatment of osteoporosis, including 10 hub genes (AKT1, ALB, IL6, MAPK3, VEGFA, JUN, CASP3, EGFR, MYC, and EGF). Pathway enrichment analysis of target proteins indicated that osteoclast differentiation, AGE-RAGE signaling pathway in diabetic complications, Wnt signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, calcium signaling pathway, and TNF signaling pathway were the specifically major pathways regulated by DHJSD against osteoporosis. Further verification based on molecular docking results showed that the small molecule compounds (Quercetin, Kaempferol, Beta-sitosterol, Beta-carotene, and Formononetin) contained in DHJSD generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes. Conclusion. This study reveals the characteristics of multi-component, multi-target, and multi-pathway of DHJSD against osteoporosis and provides novel insights for verifying the mechanism of DHJSD in the treatment of osteoporosis.

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Network Pharmacology Approach to Uncover the Mechanism Governing the Effect of Simiao Powder on Knee Osteoarthritis

BioMed Research International ◽

10.1155/2020/6971503 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Zhengquan Huang ◽

Xiaoqing Shi ◽

Xiaochen Li ◽

Li Zhang ◽

Peng Wu ◽

...

Keyword(s):

Molecular Docking ◽

Knee Osteoarthritis ◽

Signaling Pathway ◽

Protein Interaction ◽

Cell Metabolism ◽

Interaction Network ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Active Components ◽

Discovery Studio

Objective. To explore the molecular mechanism of Simiao powder in the treatment of knee osteoarthritis. Methods. Based on oral bioavailability and drug-likeness, the main active components of Simiao powder were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). GeneCard, OMIM, DisGeNET, DrugBank, PharmGkb, and the Therapeutic Target Database were used to establish target databases for knee osteoarthritis. Cytoscape software was used to construct a visual interactive network diagram of “active ingredient - action target – disease.” The STRING database was used to construct a protein interaction network and analyze related protein interaction relationships. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analysis were performed on the core targets. Additionally, Discovery Studio software was used for molecular docking verification of active pharmaceutical ingredients and disease targets. Results. Thirty-seven active components of Simiao powder were screened, including 106 common targets. The results of network analysis showed that the targets were mainly involved in regulating biological processes such as cell metabolism and apoptosis. Simiao powder components were predicted to exert their therapeutic effect on the AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, and HIF-1 signaling pathway. The molecular docking results showed that the active components of Simiao powder had a good match with the targets of IL1B, MMP9, CXCL8, MAPK8, JUN, IL6, MAPK1, EGF, VEGFA, AKT1, and PTGS2. Conclusion. Simiao powder has multisystem, multicomponent, and multitarget characteristics in treating knee osteoarthritis. Its possible mechanism of action includes inhibiting the inflammatory response, regulating immune function, and resisting oxidative stress to control the occurrence and development of the disease. Quercetin, wogonin, kaempferol, beta-sitosterol, and other active ingredients may be the material basis for the treatment of knee osteoarthritis.

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Network Pharmacology-Based Prediction of the Active Ingredients and Potential Targets of Chinese Herbal Danyu Gukang Pills for Application to Osteonecrosis of the Femoral Head Disease

10.21203/rs.3.rs-143355/v1 ◽

2021 ◽

Author(s):

Yongchang Guo ◽

Dapeng Zhang ◽

Yuju Cao ◽

Xiaoyan Feng ◽

Caihong Shen ◽

...

Keyword(s):

Molecular Docking ◽

Femoral Head ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

In Vitro Experiments ◽

Active Components

Abstract Ethnopharmacological relevanceOsteonecrosis of the femoral head (ONFH) is still a challenge for orthopedists worldwide, which may lead to disability in patients without effective treatment. A newly developed formula of Chinese medicine, Danyu Gukang Pills (DGP), was recognized to be effective for ONFH. Nevertheless, its molecular mechanisms remain to be clarified. MethodsNetwork pharmacology was adopted to detect the mechanism of DGP on ONFH. The compounds of DGP were collected from the online databases, and active components were selected based on their OB and DL index. The potential proteins of DGP were acquired from TCMSP database, while the potential genes of ONFH were obtained from Gene Cards and Pubmed Gene databases. The function of Gene and potential pathways were researched by GO and KEGG pathway enrichment analysis. The compounds-targets and targets-pathways network were constructed in an R and Cytosacpe software. The mechanism was further investigated via molecular docking. Finally, in-vitro experiments were validated in the BMSCs. ResultsA total of 2305 compounds in DGP were gained, among which, 370 were selected as active components for which conforming to criteria. Combined the network analysis, molecular docking and in-vitro experiments, the results firstly demonstrated that the treatment effect of DGP on ONFH may be closely related to HIF-1α, VEGFA and HIF-1 signaling pathway. ConclusionThe current study firstly researched the molecular mechanism of DGP on ONFH based on network pharmacology. The results indicated that DGP may exert the effect on ONFH targeting on HIF-1α and VEGFA via HIF-1 signaling pathway.

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Deciphering the Molecular Targets and Mechanisms of HGWD in the Treatment of Rheumatoid Arthritis via Network Pharmacology and Molecular Docking

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/7151634 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Wei Liu ◽

Yihua Fan ◽

Chunying Tian ◽

Yue Jin ◽

Shaopeng Du ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Docking ◽

Signaling Pathway ◽

Differentially Expressed Genes ◽

Target Genes ◽

Differentially Expressed ◽

Network Pharmacology ◽

Active Compounds ◽

Target Proteins ◽

Target Network

Background. Huangqi Guizhi Wuwu Decoction (HGWD) has been applied in the treatment of joint pain for more than 1000 years in China. Currently, most physicians use HGWD to treat rheumatoid arthritis (RA), and it has proved to have high efficacy. Therefore, it is necessary to explore the potential mechanism of action of HGWD in RA treatment based on network pharmacology and molecular docking methods. Methods. The active compounds of HGWD were collected, and their targets were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and DrugBank database, respectively. The RA-related targets were retrieved by analyzing the differentially expressed genes between RA patients and healthy individuals. Subsequently, the compound-target network of HGWD was constructed and visualized through Cytoscape 3.8.0 software. Protein-protein interaction (PPI) network was constructed to explore the potential mechanisms of HGWD on RA using the plugin BisoGenet of Cytoscape 3.8.0 software. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed in R software (Bioconductor, clusterProfiler). Afterward, molecular docking was used to analyze the binding force of the top 10 active compounds with target proteins of VCAM1, CTNNB1, and JUN. Results. Cumulatively, 790 active compounds and 1006 targets of HGWD were identified. A total of 4570 differentially expressed genes of RA with a p value <0.05 and log 2fold change > 0.5 were collected. Moreover, 739 GO entries of HGWD on RA were identified, and 79 pathways were screened based on GO and KEGG analysis. The core target gene of HGWD in RA treatment was JUN. Other key target genes included FOS, CCND1, IL6, E2F2, and ICAM1. It was confirmed that the TNF signaling pathway and IL-17 signaling pathway are important pathways of HGWD in the treatment of RA. The molecular docking results revealed that the top 10 active compounds of HGWD had a strong binding to the target proteins of VCAM1, CTNNB1, and JUN. Conclusion. HGWD has important active compounds such as quercetin, kaempferol, and beta-sitosterol, which exert its therapeutic effect on multiple targets and multiple pathways.

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A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Paeonia lactiflora Pall. On the Treatment of Alzheimer’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/8706589 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Qiang Zeng ◽

Longfei Li ◽

Yu Jin ◽

Zongzheng Chen ◽

Lihong Duan ◽

...

Keyword(s):

Molecular Docking ◽

Inflammatory Response ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Paeonia Lactiflora ◽

Active Compounds ◽

Target Proteins ◽

Underlying Mechanisms

Objective. To investigate the potential active compounds and underlying mechanisms of Paeonia lactiflora Pall. (PLP) on the treatment of Alzheimer’s disease (AD) based on network pharmacology. Methods. The active components of PLP were collected from Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible target proteins were predicted using TCMSP, SwissTargetPrediction, and STITCH databases. The putative AD-related target proteins were identified from Therapeutic Target Database (TTD), GeneCards, and MalaCards database. The compound-target-disease network interactions were established to obtain the key targets about PLP acting on AD by network topology analysis. Then, the function annotation and signaling pathways of key targets were performed by GO and KEGG enrichment analysis using DAVID tools. Finally, the binding capacity between active ingredients and key targets was validated by molecular docking using SystemsDock tools. Results. There were 7 active compounds involving in 151 predicted targets identified in PLP. Besides, a total of 160 AD-related targets were identified. Among these targets, 30 shared targets of PLP and AD were acquired. After topological analysis of the PLP potential target-AD target network, 33 key targets that were highly responsible for the therapeutic effects of PLP on AD were obtained. Further GO and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in cell apoptosis and inflammatory response and maintained the function of neurons to accomplish the anti-AD activity. The molecular docking analysis verified that the 7 active compounds had definite affinity with the key targets. Conclusions. The ameliorative effects of PLP on AD were predicted to be associated with regulating neural cell apoptosis, inflammatory response, and neurotrophy via various pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, and neurotrophin signaling pathway.

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