Mechanism of Action of Dengzhan Shengmai in Regulating Stroke from an Inflammatory Perspective: A Preliminary Analysis of Network Pharmacology

Stroke is a complicated disease with an increasing incidence and a very high mortality rate. A classical Chinese herbal medicine, Dengzhan Shengmai (DZSM), has shown to have therapeutic effects on stroke; however, its chemical basis and molecular mechanism are still unclear. In this study, a systems biology approach was applicable to elucidate the underlying mechanism of action of DZSM on stroke. All the compounds were obtained from databases, and pendant-related targets were obtained from various data platforms, including the TCM Systematic Pharmacology (TCMSP) database, TCM Integrated Database (TCMIP), High Throughput Experimental Reference Database (HERB), Comparative Toxicogenomics Database (CTD), SwissTargetPredicition, and SymMap, The Human Gene Database (GENECARD) and Comparative Toxicogenomics Database (CTD) were used for stroke disease target data, followed by network pharmacology analysis to predict the potential effect of DZSM on stroke. Animal experiments were intended to validate the underlying mechanisms. A total of 846 chemical components were compiled for the targets of DZSM drug, and quercetin, kaempferol, and Wuweizisu C are the highest chemical components compiled from DZSM. Overlapping with 375 disease-specific targets and 149 core targets, the core targets include TNF, IL-6, ALB, and AKT1, which are shown to regulate the disease process from an anti-inflammatory perspective. 198 enrichment messages were obtained by KEGG enrichment analysis, and we believe that the role of the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and IL-17 signaling pathway is more important. Based on rat experiments, we also demonstrated that DZSM could effectively modulate the inflammation level of brain infarct tissues and effectively alleviate behavioral characteristics. Grouped together, our study suggests that the combination of network pharmacology prediction and experimental validation can provide a useful tool to describe the molecular mechanisms of DZSM in Chinese medicine (TCM).

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Elucidation of the active compounds and molecular mechanisms of Smilacis Chinae Rhizoma for treatment of pelvic inflammatory disease based on network pharmacology and MMGBSA-docking

10.21203/rs.3.rs-20932/v1 ◽

2020 ◽

Author(s):

Yunsen Zhang ◽

Zikuang Zhao ◽

Wenxiang Wang ◽

Qi Li ◽

Huimin Chen ◽

...

Keyword(s):

Pelvic Inflammatory Disease ◽

Signaling Pathway ◽

Inflammatory Disease ◽

Molecular Mechanisms ◽

Binding Free Energy ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Ingredients ◽

Active Compounds ◽

Bidirectional Regulation

Abstract Background Smilacis Chinae Rhizoma (SCR) is widely used in the treatment of pelvic inflammatory disease (PID). However, its active ingredients and the mechanisms against PID remain elusive. This study aimed to clarify the active ingredients and explore their molecular mechanisms on PID. Method Network pharmacology and MMGBSA-docking exploited the active compounds and mechanisms against PID, as well as validating the binding mode of candidate targets.Results Network pharmacology revealed 32 active compounds and 718 compound-related targets mapped to 91 pathways which were clustered 7 genres (e.g., immunoregulation). C-T-P network and PPI analysis illustrated 17 PID-related targets, indicating that SCR may decrease inflammation, ameliorate fibrosis, and inhibit microorganisms via bidirectionally regulating IL-17 signaling pathway. Furthermore, active compounds were uncovered that bound to prostaglandin-endoperoxide synthase 2, matrix metalloprotein-9, lipocalin, signal transducer and activator of transcription 3, myeloperoxidase, and tumor necrosis factor. 19 active compounds (e.g., rutin (-66.43 kcal/mol), moracin M (-37.01 kcal/mol) and oxyresveratrol (-38.84 kcal/mol)) were found to show excellent binding free energy, demonstrating that H-bond, Pi electron cloud and electrostatic potential as the main binding ability to these targets. Conclusion Approach of network pharmacology and MMGBSA-docking revealed the active ingredients, such as rutin, moracin M, and oxyresveratrol, in SCR and dissected it exhibits the therapeutic eﬀects (e.g., decrease inflammation, ameliorate fibrosis, and inhibit microorganisms) of PID by the bidirectional regulation of IL-17 signaling pathway.

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System Pharmacology-Based Strategy to Investigate Core Component Group and Molecular Mechanisms of Xuefu Zhuyu Decoction in the Treatment of Gbm

10.21203/rs.3.rs-141955/v1 ◽

2021 ◽

Author(s):

Zhiying Lin ◽

Kexin Wang ◽

Runwei Yang ◽

Zhiyong Li ◽

Guozhong Yi ◽

...

Keyword(s):

Signaling Pathway ◽

Molecular Mechanisms ◽

Next Generation Sequencing Data ◽

Network Pharmacology ◽

Chemical Components ◽

Pharmacokinetic Parameters ◽

Core Component ◽

Component Group ◽

Pathogenic Genes ◽

Core Components

Abstract BackgroundXuefu Zhuyu Decoction (XFZYD) is a well-known Traditional Chinese Medicine (TCM) formula that has many pharmacological effects, including enhancing immune function, improving hemorheology and regulating blood vessels bidirectionally. Modern pharmacological and clinical studies showed that XFZYD could ameliorate curative effect of glioblastoma (GBM). The aim of this study was to interpret core components and the hidden molecular mechanisms of XFZYD on GBM. MethodsHere, a novel network pharmacology strategy, which combined pharmacological data, next generation sequencing data, pharmacokinetic parameters and a novel node importance calculation method was designed to decipher the potential therapeutic mechanism of XFZYD on GBM. The partial components in core component group (CCG) were evaluated by in vitro expriments. We identified 117 chemical components analysis through ADME screening, then component-target network and GBM related genes were integrated as the component-target-pathogenic gene (C-T-P) network. ResultsThe results show that the enriched pathways of targets in the key functional network could cover 77.92% of the enriched pathways of pathogenic genes. A novel cumulative contribution rate (CCR) calculation model was designed and captured CCG with 21 components. The statistics results indicate that 15 enriched pathways of the targets of CCG were overlap with pathogenic genes enriched pathways. Finally, some core components in CCG were validated by in vitro experiments. ConclusionThe results show that our proposed stategy for decoding CCG and infering the underlying mechanism with good reliability and accuracy. The validation results indicate that the CCG play a therapeutic role on GBM by targeting to PI3K-Akt signaling pathway and Toll-like receptor signaling pathway. Our strategy provides methodological reference for the optimization and secondary development of TCM formula.

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Molecular Mechanisms of Danhong Injection in Treatment of Pulmonary Fibrosis Based on Network Pharmacology and Experimental Validation

10.21203/rs.3.rs-590776/v1 ◽

2021 ◽

Author(s):

Di Han ◽

Yong Xu ◽

Wenpan Peng ◽

Dan Wang ◽

Tongxing Huang ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Signaling Pathway ◽

Mechanism Of Action ◽

Experimental Validation ◽

Molecular Mechanisms ◽

Interaction Analysis ◽

Network Pharmacology ◽

Mouse Lung ◽

Danhong Injection ◽

Mechanistic Investigation

Abstract Backgroud: Danhong injection has been proven to be reliable and practical in the clinical treatment of Pulmonary Fibrosis (PF), whereas the mechanism of action is unclear. The aim of this study was to investigate the mechanism of action of Danhong injection in the treatment of PF through network pharmacology and experimental validation. Methods: In this paper, multiple databases were utilized to capture the targets of Danhong injection and PF disease-related targets. The interaction network such as active ingredient-target was constructed and protein interaction analysis was performed via Cytoscape software. Bioprocess and signaling pathway analysis of the targets was carried out through DIVID database. Based on the analytical results, pharmacodynamic validation and mechanistic investigation were conducted in mice. Results: In this study, 111 compounds and common targets for diseases were filtered, with key targets involving MDM2, IL-2, CCL5, AKT1, MMP9, CASP3, MMP2, etc. The KEGG and GO enrichment analysis identified 16 significantly different signaling pathways, encompassing bioprocesses such as cell proliferation, apoptosis, programmed death and immune response. Animal experiments demonstrated that Danhong injection could reduce bleomycin-induced PF in mice, and could decrease the mRNA of AKT1 and the protein expression of p-Pi3k and p-Akt, thereby reducing apoptosis in mouse lung tissues. Conclusions: This study initially revealed that Danhong injection may inhibit apoptosis through the Pi3k/Akt signaling pathway and thus reduce PF in mice.

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A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Zuogui Yin in the Treatment of Male Infertility

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999200824112611 ◽

2020 ◽

Vol 23 ◽

Author(s):

Qi Zhao ◽

Hengheng Dai ◽

Jisheng Wang ◽

Fei Yan ◽

Guejin Jang ◽

...

Keyword(s):

Network Analysis ◽

Male Infertility ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Alternative Therapy ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Complementary And Alternative Therapy

Background and Aim: Traditional Chinese medicine (TCM), as a complementary and alternative therapy, has played increasingly important roles in clinical treatment and disease prevention. Zuogui Yin (ZGY) is one of the well-known TCM prescription used for the treatment of male infertility. To fully reveal the potential mechanisms underlying the therapeutic effects of ZGY on male infertility, a network pharmacology approach was conducted at the molecular level. Methods: Network pharmacology approach was used in this study, which mainly included active compound screening, target prediction, gene enrichment analysis and network analysis. Results: The network analysis successfully identified 148 potential active ingredients of ZGY and 155 predicted targets that were associated with male infertility. ZGY might play a role in the treatment of male infertility by regulating ten hub targets (VEGFA, CASP3 , TNF, AKT1, EGF, EGFR, IL-6, MAPK1, TP53 and PTGS2) and six pathways (TNF signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Toll-like receptor signaling pathway, VEGF signaling pathway and MAPK signaling pathway). Conclusion: This study explored the pharmacological activity and molecular mechanisms of ZGY against male infertility from a holistic perspective. The underlying molecular mechanisms were closely related to the intervention of oxidative stress and apoptosis with CASP3, TP53, AKT1 and MAPK1 being possible targets.

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Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190717124507 ◽

2019 ◽

Vol 22 (6) ◽

pp. 411-420 ◽

Cited By ~ 5

Author(s):

Xian-Jun Wu ◽

Xin-Bin Zhou ◽

Chen Chen ◽

Wei Mao

Keyword(s):

Cardiovascular Disease ◽

Cardiovascular Diseases ◽

Signaling Pathway ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Therapeutic Effects ◽

Pathway Enrichment ◽

Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

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Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model

Chinese Medicine ◽

10.1186/s13020-021-00446-x ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Jiye Chen ◽

Yongjian Zhang ◽

Yongcheng Wang ◽

Ping Jiang ◽

Guofeng Zhou ◽

...

Keyword(s):

Signaling Pathway ◽

Rat Model ◽

Experimental Studies ◽

Matrix Metalloproteinase 2 ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Therapeutic Effects ◽

Active Ingredients ◽

Active Compounds ◽

Guizhi Decoction

Abstract Background Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. Methods The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. Results A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C–C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1β, MMP-2 and MMP-9 in rats. Conclusion The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

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Network Pharmacology Study of The Mechanism of Anti-Pneumonia Action Mechanism of Gentiana Rhodantha Franch

10.21203/rs.3.rs-539959/v1 ◽

2021 ◽

Author(s):

Jun Luo ◽

Xiusheng Tang ◽

Guotao Shu ◽

Dongxin Tang ◽

Jia Yu ◽

...

Keyword(s):

Chinese Medicine ◽

Signaling Pathway ◽

High Throughput Sequencing ◽

Biological Information ◽

Network Pharmacology ◽

Chemical Components ◽

Sequencing Analysis ◽

Data Set ◽

Annotation Database ◽

Functional Richness

Abstract Background: Serum dragon bile is a Chinese medicine used to treat pneumonia, but its mechanism of action is not clear. Meanwhile, due to the development of microarray and RNA‐sequencing technology, high-throughput sequencing analysis is being used increasingly, and it has been applied as an indispensable tool in many medical fields. Therefore, in this article, we want to employed the bioinformatics approach to explore the relevant pharmacological mechanism of dragon serum bile in the treatment of pneumonia through network pharmacology.Methods: In this paper, the active chemical composition and action target of serum dragon bile are obtained through the pharmacology database (TCMSP) of Chinese medicine system and the literature, and the data set of the intersection of active ingredient and disease target is established, and the protein interoperability network of serum gallbladder action target and pneumonia action target is analyzed by using protein interaction network (PPI). Using the Biological Information Annotation Database (DAVID) for gene ontology (GO) functional richness analysis and based on kyoto Gene and Genomics Encyclopedia (KEGG) pathogenic rich analysis, to predict the mechanism of the role of seroclon bile against pneumonia. Results: Through the network pharmacological prediction, it is shown that the main chemical components of serum dragon bile are quercetin, isoorientin, luteolin, Stigmasterol, vanillic acid, etc, all of which have anti-pneumonia effects. The anti-pneumonia effect of serum dragon bile is mainly regulated by pathways in cancer, Bradder cancer, TNF signaling pathway, Hepatitis B and Non-small cell lung cancer, among which the TNF signaling pathway is more associated with pneumonia. Conclusions: It is concluded from the network pharmacological prediction that serum dragon bile may play an anti-pneumonia role by promoting apoptosis, survival, immunity, etc. Its anti-pneumonia path is closely related to key targets IL6, FOS, CASP3 and AKT1. This study provides theoretical support for the follow-up study of the anti-pneumonia mechanism of serum gentian bile.

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Network Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of the Drug Pair Astragalus-Angelica for Treatment of Male Infertility

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8281506 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Feng Zhao ◽

Yingjun Deng ◽

Guanchao Du ◽

Shengjing Liu ◽

Jun Guo ◽

...

Keyword(s):

Male Infertility ◽

Signaling Pathway ◽

Mechanism Of Action ◽

Protein Interactions ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Protein Protein Interactions ◽

Drug Pair ◽

Effective Components ◽

New Ideas

Background. The traditional Chinese medicines Astragalus and Angelica are often combined to treat male infertility, but the specific therapeutic mechanism is not clear. Therefore, this study applies a network pharmacology approach to investigate the possible mechanism of action of the drug pair Astragalus-Angelica (PAA) in the treatment of male infertility. Methods. Relevant targets for PAA treatment of male infertility are obtained through databases. Protein-protein interactions (PPIs) are constructed through STRING database and screen core targets, and an enrichment analysis is conducted through the Metascape platform. Finally, molecular docking experiments were carried out to evaluate the affinity between the target protein and the ligand of PAA. Results. The active ingredients of 112 PAA, 980 corresponding targets, and 374 effective targets of PAA for the treatment of male infertility were obtained, which are related to PI3K-Akt signaling pathway, HIF-1 signaling pathway, AGE-RAGE signaling pathway, IL-17 signaling pathway, and thyroid hormone signaling pathway. Conclusion. In this study, using a network pharmacology method, we preliminarily analyzed the effective components and action targets of the PAA. We also explored the possible mechanism of action of PAA in treating male infertility. They also lay a foundation for expanding the clinical application of PAA and provide new ideas and directions for further research on the mechanisms of action of the PAA and its components for male infertility treatment.

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Network Pharmacology of Yougui Pill Combined with Buzhong Yiqi Decoction for the Treatment of Sexual Dysfunction

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1243743 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Yangyun Wang ◽

Wandong Yu ◽

Chaoliang Shi ◽

Wei Jiao ◽

Junhong Li ◽

...

Keyword(s):

Sexual Dysfunction ◽

Signaling Pathway ◽

Herbal Medicines ◽

Mapk Signaling ◽

Glycyrrhetinic Acid ◽

Network Pharmacology ◽

Receptor Interaction ◽

Chemical Components ◽

Target Proteins ◽

Yougui Pill

Purpose. We aimed to find the possible key targets of Yougui pill and Buzhong Yiqi decoction for the treatment of sexual dysfunction. Materials and Methods. The composition of Yougui pill combined with Buzhong Yiqi decoction was obtained, and its effective components of medicine were screened using ADME; the component target proteins were predicted and screened based on the TCMSP and BATMAN databases. Target proteins were cross-validated using the CTD database. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins using the Cytoscape plugin ClueGO + CluePedia and the R package clusterProfiler, respectively. Subsequently, protein-protein interaction (PPI) analyses were conducted using the STRING database. Finally, a pharmacological network was constructed. Results. The pharmacological network contained 89 nodes and 176 relation pairs. Among these nodes, there were 12 for herbal medicines (orange peel, licorice, Eucommia, Aconite, Astragalus, Chinese wolfberry, yam, dodder seed, ginseng, Cornus officinalis, Rehmannia, and Angelica), 9 for chemical components (18-beta-glycyrrhetinic acid, carvacrol, glycyrrhetinic acid, higenamine, nobilin, quercetin, stigmasterol, synephrine, and thymol), 62 for target proteins (e.g., NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53), and 6 for pathways (MAPK signaling pathway, proteoglycans in cancer, dopaminergic synapse, thyroid hormone signaling pathway, cAMP signaling pathway, and neuroactive ligand-receptor interaction). Conclusion. NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53 may be important targets for the key active elements in the decoction combining Yougui pill and Buzhong Yiqi. Furthermore, these target proteins are relevant to the treatment of sexual dysfunction, probably via pathways associated with cancer and signal transduction.

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A Network Pharmacology Approach to Uncover the Mechanisms of Shen-Qi-Di-Huang Decoction against Diabetic Nephropathy

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/7043402 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 9

Author(s):

Sha Di ◽

Lin Han ◽

Qing Wang ◽

Xinkui Liu ◽

Yingying Yang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Interaction Network ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Protein Protein Interaction ◽

Regulation Of Blood Pressure ◽

Protein Protein Interaction Network

Shen-Qi-Di-Huang decoction (SQDHD), a well-known herbal formula from China, has been widely used in the treatment of diabetic nephropathy (DN). However, the pharmacological mechanisms of SQDHD have not been entirely elucidated. At first, we conducted a comprehensive literature search to identify the active constituents of SQDHD, determined their corresponding targets, and obtained known DN targets from several databases. A protein-protein interaction network was then built to explore the complex relations between SQDHD targets and those known to treat DN. Following the topological feature screening of each node in the network, 400 major targets of SQDHD were obtained. The pathway enrichment analysis results acquired from DAVID showed that the significant bioprocesses and pathways include oxidative stress, response to glucose, regulation of blood pressure, regulation of cell proliferation, cytokine-mediated signaling pathway, and the apoptotic signaling pathway. More interestingly, five key targets of SQDHD, named AKT1, AR, CTNNB1, EGFR, and ESR1, were significant in the regulation of the above bioprocesses and pathways. This study partially verified and predicted the pharmacological and molecular mechanisms of SQDHD on DN from a holistic perspective. This has laid the foundation for further experimental research and has expanded the rational application of SQDHD in clinical practice.

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