scholarly journals Mechanisms and Molecular Targets of the Tao-Hong-Si-Wu-Tang Formula for Treatment of Osteonecrosis of Femoral Head: A Network Pharmacology Study

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Fanyu Fu ◽  
Zeqing Huang ◽  
Hengli Ye ◽  
Biao Tan ◽  
Rongtian Wang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Femoral Head ◽  
Traditional Chinese Medicine ◽  
Drug Targets ◽  
Target Genes ◽  
Molecular Targets ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Osteonecrosis Of Femoral Head ◽  
Intersection Analysis

The Tao-Hong-Si-Wu-Tang (THSWT) formula, a classic prescription of traditional Chinese medicine, has long been used for the treatment of osteonecrosis of femoral head (ONFH). However, its mechanisms of action and molecular targets are not comprehensively clear. In the present study, the Traditional Chinese Medicine System Pharmacology (TCMSP) database was employed to retrieve the active compounds of each herb included in the THSWT formula. After identifying the drug targets of active compounds and disease targets of ONFH, intersection analysis was conducted to screen out the shared targets. The protein-protein network of the shared targets was built for further topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were then carried out. A gene pathway network was constructed to screen the core target genes. We identified 61 active compounds, 155 drug targets, and 5443 disease targets. However, intersection analysis only screened out 37 shared targets. Kaempferol, luteolin, and baicalein regulated the greatest number of targets associated with ONFH. The THSWT formula may regulate osteocyte function through specific biological processes, including responses to toxic substances and oxidative stress. The regulated pathways included the relaxin, focal adhesion, nuclear factor-κB, toll-like receptor, and AGE/RAGE signaling pathways. RELA, VEGFA, and STAT1 were the important target genes in the gene network associated with the THSWT formula for the treatment of ONFH. Therefore, the present study suggested that the THSWT formula has an action mechanism involving multiple compounds and network targets for the treatment of ONFH.

scholarly journals A Network Pharmacology-Based Study on the Anti-Lung Cancer Effect of Dipsaci Radix

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Jiayan Wu ◽  
Shengkun Hong ◽  
Xiankuan Xie ◽  
Wangmi Liu
Keyword(s):  
Lung Cancer ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Active Compounds

Objective. Dipsaci Radix (DR) has been used to treat fracture and osteoporosis. Recent reports have shown that myeloid cells from bone marrow can promote the proliferation of lung cancer. However, the action and mechanism of DR has not been well defined in lung cancer. The aim of the present study was to define molecular mechanisms of DR as a potential therapeutic approach to treat lung cancer. Methods. Active compounds of DR with oral bioavailability ≥30% and drug-likeness index ≥0.18 were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform. The potential target genes of the active compounds and bone were identified by PharmMapper and GeneCards, respectively. The compound-target network and protein-protein interaction network were built by Cytoscape software and Search Tool for the Retrieval of Interacting Genes webserver, respectively. GO analysis and pathway enrichment analysis were performed using R software. Results. Our study demonstrated that DR had 6 active compounds, including gentisin, sitosterol, Sylvestroside III, 3,5-Di-O-caffeoylquinic acid, cauloside A, and japonine. There were 254 target genes related to these active compounds as well as to bone. SRC, AKT1, and GRB2 were the top 3 hub genes. Metabolisms and signaling pathways associated with these hub genes were significantly enriched. Conclusions. This study indicated that DR could exhibit the anti-lung cancer effect by affecting multiple targets and multiple pathways. It reflects the traditional Chinese medicine characterized by multicomponents and multitargets. DR could be considered as a candidate for clinical anticancer therapy by regulating bone physiological functions.

scholarly journals Exploring the mechanism of Astragalus membranaceus against uterine fibroids based on network pharmacology

2021 ◽  
Author(s):  
qiu tiantian ◽  
Li DongHua ◽  
Liu Yu ◽  
Gao LiFang ◽  
Wei Chao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Mechanism Of Action ◽  
Regulatory Network ◽  
Drug Targets ◽  
Target Genes ◽  
Uterine Fibroids ◽  
Network Pharmacology ◽  
Ppi Network

Abstract Backgroud: Uterine fibroids (ULs) are the most common benign tumors of the reproductive tract in gynecology and their clinical presentations include menorrhagia, pelvic pressure, dysmenorrhea, and anemia. Surgical resection and the hormonal drug administration are the primary treatment. The plant Astragalus membranaceus (astragalus) has a long history of use in traditional Chinese medicine and studies have shown that it has antitumor effects. However, the role and mechanism of astragalus in ULs are not completely clear. The present study aimed to investigate the astragalus mechanism of action against ULs based on network pharmacology approach, in order to provid insights for the development of a safe and effective drug for the ULs treatment.Methods: The astragalus active ingredients and the potential drug targets were screened by the Traditional Chinese Medicine System Pharmacology Database and Analytical Platform (TCMSP). The gene expression profiles of ULs were obtained from Gene Expression Omnibus (GEO). The intersection of astragalus components target genes and differentially expressed genes between UL and normal patients were obtained using Perl software to provide the astragalus-ULs drug regulatory network. The protein–protein interaction (PPI) network was established using the STRING online database and Cytoscape software, followed by the topological properties analysis of the PPI networks. GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were conducted by R software. The KEGG relational network was constructed using Cytoscape software. Results: A total of 21 astragalus active ingredients and 406 drug targets were obtained from the TCMSP. Seventeen of these targets overlap with ULs disease targets and were considered potential targets for the ULs treatment by astragalus. The analysis of the regulatory network showed that the astragalus active components with the most targets are quercetin, kaempferol, mangiferin, tetrodotoxin and isorhamnetin. Target genes with the highest Dgree values obtained from the PPI network analysis are estrogen receptor 1 (ESR1), tumor suppressor factor p53 (TP53), neurotrophic tyrosine kinase receptor 1 (NTRK1) and E3 ubiquitin ligase protein (CUL3). GO and KEGG enrichment analyses indicate that these targets are mainly involved in biological processes related to cellular response to reactive oxygen species, oxidative stress and response to lipopolysaccharides. The main signal transduction pathways involved include the IL-17 and TNF signaling pathways, the AGE-RAGE signaling pathway in diabetic complications and proteoglycans in cancer.Conclusions: The present study demonstrates that the astragalus therapeutic use against ULs have multicomponent and multi-target properties, providing a novel approach to further investigate the astragalus mechanism of action in the treatment of ULs.

scholarly journals Systematic Elucidation of the Mechanism of Oroxylum indicum via Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Junmin Chen ◽  
Jianyong Chen ◽  
Jingrong Lu
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Drug Targets ◽  
Target Genes ◽  
Wide Spectrum ◽  
Network Pharmacology ◽  
Network Analyses ◽  
Oroxylum Indicum ◽  
Potential Drug Targets ◽  
Pathway Networks

Oroxylum indicum (O. indicum) is an important traditional Chinese medicine that exerts a wide spectrum of pharmacological activities. However, the pharmacological effect of O. indicum and its mechanism of action have not to be systematically elucidated yet. In this study, the druggability for active compounds of O. indicum was assessed via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the potential drug targets of O. indicum were identified using PharmMapper database. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed via WebGestalt. Drug-target-pathway networks were constructed using Cytoscape to give a visual view. Our findings revealed that O. indicum has extremely superb druggability with 41 putative identified target genes. GO, KEGG, and network analyses showed that these targets were associated with inflammatory immunoreactions, cancer, and other biological processes. In summary, O. indicum is predicted to target multiple genes/proteins and pathways that shape a network which can exert systematic pharmacological effects.

scholarly journals Network Pharmacology Reveals the Molecular Mechanism of Cuyuxunxi Prescription in Promoting Wound Healing in Patients with Anal Fistula

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yin Qu ◽  
Zhijun Zhang ◽  
Yafeng Lu ◽  
De Zheng ◽  
Yang Wei
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Target Genes ◽  
Herbal Medicines ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Surgical Wound ◽  
Active Compounds

Background. The healing process of the surgical wound of anal fistulotomy is much slower because of the presence of stool within the wound. Cuyuxunxi (CYXX) prescription is a Chinese herbal fumigant that is being used to wash surgical wound after anal fistulotomy. This study aimed at investigating the molecular mechanism of CYXX prescription using a network pharmacology-based strategy. Materials and Methods. The active compounds in each herbal medicine were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and in Traditional Chinese Medicine Integrated Database (TCMID) analysis platform based on the criteria of oral bioavailability ≥40% and drug-likeness ≥0.2. The disease-related target genes were extracted from the Comparative Toxicogenomics Database. Protein-protein interaction network was built for the overlapped genes as well as functional enrichment analysis. Finally, an ingredient-target genes-pathway network was built by integrating all information. Results. A total of 375 chemical ingredients of the 5 main herbal medicines in CYXX prescription were retrieved from TCMSP database and TCMID. Among the 375 chemical ingredients, 59 were active compounds. Besides, 325 target genes for 16 active compounds in 3 herbal medicines were obtained. Functional enrichment analysis revealed that these overlapped genes were significantly related with immune response, biosynthesis of antibiotics, and complement and coagulation cascades. A comprehensive network which contains 133 nodes (8 disease nodes, 3 drug nodes, 8 ingredients, 103 target gene nodes, 7 GO nodes, and 4 pathway nodes) was built. Conclusion. The network built in this study might aid in understanding the action mechanism of CYXX prescription at molecular level to pathway level.

scholarly journals Research on Active Compounds of Huanglian Jiedu Decoction for the Treatment of Corona Virus Disease 2019 Based on Network Pharmacology and Molecular Docking

2020 ◽  
Author(s):  
Leping Liu ◽  
Xinyi Xu ◽  
Xueshuai Cao ◽  
Xi Long ◽  
Yanwei Luo ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathways ◽  
Target Genes ◽  
Virus Disease ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Active Compounds ◽  
Corona Virus

Abstract Background Huanglian Jiedu Decoction (HLJDD) is a traditional Chinese prescription for the treatment of influenza, inflammation and other ailments related to heat-syndrome, a typical pathological symptom in Traditional Chinese Medicine. It was recommended as one of the basic prescriptions among the Proposed Diagnoses and Treatment issued by China’s National Health Commission. In this work we investigated the molecular mechanism of action of Huanglian Jiedu Decoction in the treatment of Corona Virus Disease 2019 (COVID-19) through network pharmacology and molecular docking approaches. Methods The chemical constituents and action targets of Coptis chinensis, Scutellaria baicalensis, Phellodendron amurense, Gardenia jasminoides in HLJDD were retrieved on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The database of UniProt and GeneCards were used to query the target genes that corresponding to the active compounds, and then a compound-target network was constructed using Cytoscape 3.7.2. GO database was used to annotate GO functions. Reactome was used to analyze KEGG enrichment pathway, predicting the possible mechanisms of active compounds. DAVID database was used to analysis the tissue enrichment. The main active ingredient is molecularly docked with the SARS-CoV-2, ACE2 and TMPRSS2. Results We screened 84 compounds and obtained 341 corresponding target genes in the network. Gene annotation showed that the targets were involved mainly in 457 biological functions. 306 signaling pathways was enriched, involving chemokine and cytokine signaling pathways that mediate inflammation, interferon-γ signaling pathway, p53 pathway. And the targets mainly distributed in the lung liver and placenta, involving a variety of immune cells, such as T cells, B cells. The molecular docking results showed that core compounds such as beta-sitosterol, stigmasterol and quercetin had high affinity with SARS-CoV-2, ACE2 and TMPRSS2, which was comparable with drugs like abidol used to COVID-19 treatment by. Conclusions The active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as VEGF, NOS2, IL6, MMP9, IL10, and TGFB1.

scholarly journals Molecular Targets and Pathways Contributing to the Effects of Wenxin Keli on Atrial Fibrillation Based on a Network Pharmacology Approach

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yujie Zhang ◽  
Xiaolin Zhang ◽  
Xi Zhang ◽  
Yi Cai ◽  
Minghui Cheng ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Clinical Symptoms ◽  
Chemical Constituents ◽  
Molecular Targets ◽  
Network Pharmacology ◽  
Systems Pharmacology

Background. Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with high rates of mortality and morbidity. The traditional Chinese medicine Wenxin Keli (WXKL) can effectively improve clinical symptoms and is safe for the treatment of AF. However, the active substances in WXKL and the molecular mechanisms underlying its effects on AF remain unclear. In this study, the bioactive compounds in WXKL, as well as their molecular targets and associated pathways, were evaluated by systems pharmacology. Materials and Methods. Chemical constituents and potential targets of WXKL were obtained via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). The TTD, DrugBank, DisGeNET, and GeneCards databases were used to collect AF-related target genes. Based on common targets related to both AF and WXKL, a protein interaction network was generated using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment analyses were performed. Network diagrams of the active component-target and protein-protein interactions (PPIs) were constructed using Cytoscape. Results. A total of 30 active ingredients in WXKL and 219 putative target genes were screened, including 83 genes identified as therapeutic targets in AF; these overlapping genes were considered candidate targets for subsequent analyses. The effect of treating AF was mainly correlated with the regulation of target proteins, such as IL-6, TNF, AKT1, VEGFA, CXCL8, TP53, CCL2, MMP9, CASP3, and NOS3. GO and KEGG analyses revealed that these targets are associated with the inflammatory response, oxidative stress reaction, immune regulation, cardiac energy metabolism, serotonergic synapse, and other pathways. Conclusions. This study demonstrated the multicomponent, multitarget, and multichannel characteristics of WXKL, providing a basis for further studies of the mechanism underlying the beneficial effects of WXKL in AF.

scholarly journals A network pharmacology-based approach to explore the active ingredients and molecular mechanism of Lei-gong-gen formula granule on a spontaneously hypertensive rat model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qiaofeng Li ◽  
Taijin Lan ◽  
Songhua He ◽  
Weiwei Chen ◽  
Xiaolan Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Nicotinic Acid ◽  
Signaling Pathway ◽  
Antihypertensive Effect ◽  
Spontaneously Hypertensive Rat ◽  
Shikimic Acid ◽  
Network Pharmacology ◽  
Active Compounds

Abstract Background Lei-gong-gen formula granule (LFG) is a folk prescription derived from Zhuang nationality, the largest ethnic minority among 56 nationalities in China. It consists of three herbs, namely Eclipta prostrata (L.) L., Smilax glabra Roxb, and Centella asiatica (L.) Urb. It has been widely used as health protection tea for hundreds of years to prevent hypertension in Guangxi Zhuang Autonomous Region. The purpose of this study is to validate the antihypertensive effect of LFG on the spontaneously hypertensive rat (SHR) model, and to further identify the effective components and anti-hypertension mechanism of LFG. Methods The effects of LFG on blood pressure, body weight, and heart rate were investigated in vivo using the SHR model. The levels of NO, ANG II, and ET-1 in the serum were measured, and pathological changes in the heart were examined by H&E staining. The main active components of LFG, their corresponding targets, and hypertension associated pathways were discerned through network pharmacology analysis based on the Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Then the predicted results were further verified by molecular biology experiments such as RT-qPCR and western blot. Additionally, the potential active compounds were predicted by molecular docking technology, and the chemical constituents of LFG were analyzed and identified by UPLC-QTOF/MS technology. Finally, an in vitro assay was performed to investigate the protective effects of potential active compounds against hydrogen peroxide (H2O2) induced oxidative damage in human umbilical vein endothelial cells (HUVEC). Results LFG could effectively reduce blood pressure and increase serum NO content in SHR model. Histological results showed that LFG could ameliorate pathological changes such as cardiac hypertrophy and interstitial inflammation. From network pharmacology analysis, 53 candidate active compounds of LFG were collected, which linked to 765 potential targets, and 828 hypertension associated targets were retrieved, from which 12 overlapped targets both related to candidate active compounds from LFG and hypertension were screened and used as the potential targets of LFG on antihypertensive effect. The molecular biology experiments of the 12 overlapped targets showed that LFG could upregulate the mRNA and protein expressions of NOS3 and proto-oncogene tyrosine-protein kinase SRC (SRC) in the thoracic aorta. Pathway enrichment analysis showed that the PI3K-AKT signaling pathway was closely related to the expression of NOS3 and SRC. Moreover, western blot results showed that LFG significantly increased the protein expression levels of PI3K and phosphorylated AKT in SHR model, suggesting that LFG may active the PI3K-AKT signaling pathway to decrease hypertension. Molecular docking study further supported that p-hydroxybenzoic acid, cedar acid, shikimic acid, salicylic acid, nicotinic acid, linalool, and histidine can be well binding with NOS3, SRC, PI3K, and AKT. UPLC-QTOF/MS analysis confirmed that p-hydroxybenzoic acid, shikimic acid, salicylic acid, and nicotinic acid existed in LFG. Pre-treatment of HUVEC with nicotinic acid could alleviate the effect on cell viability induced by H2O2 and increase the NO level in cell supernatants. Conclusions LFG can reduce the blood pressure in SHR model, which might be attributed to increasing the NO level in serum for promoting vasodilation via upregulating SRC expression level and activating the PI3K-AKT-NOS3 signaling pathway. Nicotinic acid might be the potential compound for LFG antihypertensive effect.

scholarly journals Exploring the Mechanisms of Lian Hua Qing Wen Capsule against COVID-19 by Network Pharmacology and Molecular Docking Approach

2020 ◽  
Author(s):  
Li Chen ◽  
Hua Qu ◽  
Yu Tan ◽  
Tao Han Wu ◽  
Zhuo Da Shi
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Active Compounds ◽  
Related Target ◽  
Docking Approach ◽  
Omim Database

Abstract Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) disease has led to a wide-spread global pandemic. There is no specific antiviral drug proven effective for the treatment of patients with COVID-19 at present. Combination of western and traditional Chinese medicine (TCM) is recommended, and Lian Hua Qing Wen (LHQW) capsule is a basic prescription and widely used to treat COVID-19 in China. However, the mechanisms of LHQW capsule treating COVID-19 are not clear. The aim of the study is to explore the mechanisms of LHQW capsule treating COVID-19 based on network pharmacy and molecular docking approach. Methods The active compounds and targets of LHQW capsule were obtained from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). COVID-19 related target genes were obtained from GeneCards database and OMIM database. Protein–protein interaction (PPI) networks of LHQW capsule targets and COVID-19-related genes were visualized and merged to identify the candidate targets for LHQW capsule treating COVID-19. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed. The hub genes involved in the gene-related pathways were screened and their corresponding compounds were used for in vitro validation of molecular docking predictions.Results A total of 185 active compounds of LHQW capsule were screened out, and 263 targets were predicted. Third hundred and fifty-two COVID-19 related target genes were obtained from GeneCards database and OMIM database. GO functional enrichment analysis showed that the biological processes of LHQW capsule treating COVID-19 were closely linked with the regulation of inflammation, immunity, cytokines production, vascular permeability, oxidative stress and apoptosis. KEGG enrichment analysis revealed that the pathways of LHQW capsule treating COVID-19 were significantly enriched in AGE−RAGE signaling pathway in diabetic complications, Kaposi sarcoma−associated herpesvirus infection, TNF, IL−17, and Toll−like receptor (TLR) signaling pathway. The hub targets genes in the gene-related pathways analysis of LHQW capsule treating COVID-19 included MAPK1, MAPK3, RELA, IL-6 and CASP8, which closely associated with inflammation, cytokines storm and apoptosis. Finally, molecular docking showed that top 5 compounds of LHQW capsule also had good binding activities to the important targets in COVID-19.Conclusions The mechanisms of LHQW capsule treating COVID-19 may involve in inhibiting inflammatory response, cytokine storm and virus infection, and regulating immune reactions, apoptosis and endothelial barrier.

scholarly journals Network Pharmacology Analysis of Traditional Chinese Medicine Formula Xiao Ke Yin Shui Treating Type 2 Diabetes Mellitus

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Jiewen Zhou ◽  
Qiuyan Wang ◽  
Zhinan Xiang ◽  
Qilin Tong ◽  
Jun Pan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Target Genes ◽  
Network Pharmacology ◽  
Ppi Networks ◽  
Chinese Medicine Formula ◽  
Herb Extracts

Xiao Ke Yin Shui (XKYS) formula is a traditional Chinese medicine formula treating type 2 diabetes mellitus (T2DM). XKYS formula consists of four herbs, i.e., Coptidis rhizoma, Liriopes radix, bitter melon, and Cassiae semen. Herein, the chemical profiles of four herb extracts were investigated, and further analysis of the underlying mechanism of XKYS formula treating T2DM was performed using network pharmacology. The main components were selected for our network-based research. Targets of XKYS formula were mainly collected from two databases, SwissTargetPrediction and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the text-mining method was also implemented. T2DM relating genes and therapeutic targets were collected from five databases. Subsequently, STRING and Cytoscape were employed for the analysis of protein-protein interaction (PPI) networks. Functional annotation and pathway analysis were conducted to investigate the functions and relating pathways of target genes. The content of 12 compounds in the herb extracts was determined. With the analysis of PPI networks, a total of 76 genes were found to be important nodes and could be defined as the main target genes regulated by XKYS formula in the treatment of T2DM and its complications. Components in XKYS formula mainly regulate proteins including protein kinase B (Akt), phosphatidylinositol 3-kinase (PI3K), insulin receptor substrate (IRS), and tumor necrosis factor (TNF). XKYS formula exerts therapeutic effects in a synergetic manner and exhibits antidiabetic effect mainly via reducing insulin resistance. These findings could be guidelines in the further investigation of this formula.

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