scholarly journals Exploring the Pharmacological Mechanism of Liuwei Dihuang Decoction for Diabetic Retinopathy: A Systematic Biological Strategy-Based Research

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Mengxia Yuan ◽  
Qi He ◽  
Zhiyong Long ◽  
Xiaofei Zhu ◽  
Wang Xiang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Signaling Pathways ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Ppi Network ◽  
Pharmacological Mechanism ◽  
Target Network ◽  
Erbb Signaling

Objective. To explore the pharmacological mechanism of Liuwei Dihuang decoction (LDD) for diabetic retinopathy (DR). Methods. The potential targets of LDD were predicted by PharmMapper. GeneCards and other databases were used to collect DR genes. Cytoscape was used to construct and analyze network DR and LDD’s network, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were carried out to verify the results of systematic pharmacology. Results. Five networks were constructed and analyzed: (1) diabetic retinopathy genes’ PPI network; (2) compound-compound target network of LDD; (3) LDD-DR PPI network; (4) compound-known target network of LDD; (5) LDD known target-DR PPI network. Several DR and treatment-related targets, clusters, signaling pathways, and biological processes were found. Animal experiments found that LDD can improve the histopathological changes of the retina. LDD can also increase erythrocyte filtration rate and decrease the platelet adhesion rate ( P < 0.05 ) and decrease MDA and TXB2 ( P < 0.05 ). Compared with the model group, the retinal VEGF and HIF-1α expression in the LDD group decreased significantly ( P < 0.05 ). Conclusion. The therapeutic effect of LDD on DR may be achieved by interfering with the biological processes (such as response to insulin, glucose homeostasis, and regulation of angiogenesis) and signaling pathways (such as insulin, VEGF, HIF-1, and ErbB signaling pathway) related to the development of DR that was found in this research.

scholarly journals Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Yi Chen ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathways ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemic

Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained.Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR.Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p &lt; 0.05).Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study.

scholarly journals The Effect of Hedysarum multijugum Maxim.-Chuanxiong rhizoma Compound on Ischemic Stroke: A Research Based on Network and Experimental Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-24
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Yongmei Shi ◽  
Xiaofei Zhu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Ischemic Stroke ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathways ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Buyang Huanwu Decoction

Background. Hedysarum multijugum Maxim.-Chuanxiong rhizoma compound (HCC) is a common herbal formula modified from Buyang Huanwu decoction. Clinical trials have demonstrated its therapeutic potential for ischemic stroke (IS). However, the mechanism of HCC remains unclear. Methods. The HCC’s components were collected from the TCMSP database and TCM@Taiwan database. After that, the HCC’s compound targets were predicted by PharmMapper. The IS-related genes were obtained from GeneCards, and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from the String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis and the Cytoscape 3.7.2 was utilized to construct and analyze the networks. Finally, a series of animal experiments were carried out to validate the prediction results of network pharmacology. The expressions of GRP78, p-PERK, and CHOP proteins and mRNAs in different time periods after HCC intervention were detected by Western blot, immunohistochemistry, and RT-qPCR. Results. A total of 440 potential targets and 388 IS genes were obtained. The results of HCC-IS PPI network analysis showed that HCC may regulate IS-related targets (such as ALB, AKT1, MMP9, IGF1, and CASP3), biological processes (such as endoplasmic reticulum stress, inflammation modules, hypoxia modules, regulation of neuronal apoptosis and proliferation, and angiogenesis), and signaling pathways (such as PI3K-Akt, FoxO, TNF, HIF-1, and Rap1 signaling). The animal experiments showed that HCC can improve the neurobehavioral scores and protect the neurons of IS rats ( P < 0.05 ). HCC inhibited the expression of p-PERK in the PERK pathway from 12 h after surgery, significantly promoted the expression of GRP78 protein, and inhibited the expression of CHOP protein after surgery, especially at 24 h after surgery ( P < 0.05 ). The results of RT-qPCR showed that HCC can significantly reduce the expression of CHOP mRNA in the neurons in the CA1 region of the hippocampus 72 h after MCAO ( P < 0.05 ). Conclusion. HCC may achieve a role in the treatment of IS by intervening in a series of targets, signaling pathways, and biological processes such as inflammation, oxidative stress, endoplasmic reticulum stress, and angiogenesis.

scholarly journals Systems Pharmacological Approach to Investigate the Mechanism of Acori Tatarinowii Rhizoma for Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Zhenyan Song ◽  
Fang Yin ◽  
Biao Xiang ◽  
Bin Lan ◽  
Shaowu Cheng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Biological Processes ◽  
Pathway Enrichment ◽  
Study Results ◽  
Target Network ◽  
Anti Inflammatory

In traditional Chinese medicine (TCM), Acori Tatarinowii Rhizoma (ATR) is widely used to treat memory and cognition dysfunction. This study aimed to confirm evidence regarding the potential therapeutic effect of ATR on Alzheimer’s disease (AD) using a system network level based in silico approach. Study results showed that the compounds in ATR are highly connected to AD-related signaling pathways, biological processes, and organs. These findings were confirmed by compound-target network, target-organ location network, gene ontology analysis, and KEGG pathway enrichment analysis. Most compounds in ATR have been reported to have antifibrillar amyloid plaques, anti-tau phosphorylation, and anti-inflammatory effects. Our results indicated that compounds in ATR interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by ATR are elevated significantly in heart, brain, and liver. Our results suggest that the anti-inflammatory and immune system enhancing effects of ATR might contribute to its major therapeutic effects on Alzheimer’s disease.

System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

2020 ◽  
Author(s):  
Zhiqiang Liu ◽  
Bolong Wang
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Kegg Pathway ◽  
Inflammatory Diseases ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Pharmacological Effects ◽  
Ppi Network ◽  
Pathway Enrichment ◽  
Pharmacological Mechanism

Abstract Background: Jianghuang (JH) is a popular ingredient in blood-regulating traditional Chinese Medicine (TCM) that could be effective for the treatment of various diseases. We demonstrate the compatibility laws and system pharmacological mechanisms of the key formula containing JH by leveraging data mining of bioinformatics databases.Material/Methods: The compatibility laws of blood-regulating formulae containing JH from the Chinese Traditional Medicine Formula Dictionary were analyzed using a generalized rule induction (GRI) algorithm implemented. The putative target gene and miRNA were retrieved via a combination of the Arrowsmith knowledge discovery tool and FunRich 3.1.3. System pharmacological mechanisms are traced by their protein-protein interaction (PPI) network, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using Uniprot, the Human Protein Atlas (HPA), STRING 11.0, and KOBAS 3.0.Results: We found that the JH-CX-DG formula (Ligusticum chuanxiong-Angelica sinensis) could represent a key formula containing JH in blood-regulating TCM formulae. The JH-CX-DG formula was observed to directly target AKT, TLR4, caspase-3, PI3K, mTOR, p38 MAPK, VEGF, iNOS, Nrf2, BDNF, NF-κB, Bcl-2, and Bax 13 targets and regulate targets through 13 miRNA. The PPI network and KEGG pathway enrichment analysis showed that the JH-CX-DG formula possess potential pharmacological effects including anti-inflammatory, improving microcirculation, and anti-tumor through the regulation of multiple pathways including PI3K/Akt, MAPK, Toll-like receptor, T cell receptor, EGFR, VEGFR, Apoptosis, HIF-1 (p < 0.05).Conclusion: The JH-CX-DG formula can exert beneficial pharmacological effects through multi-target and multi-pathway interactions. It can be effectively administered for the treatment of inflammatory diseases, microcirculation disorders, cardiovascular disease, and cancer. We found a new effective drug formula through analyzing the compatibility law and systemic pharmacological mechanism of JH. Our study provides a theoretical basis and directions for subsequent research on the JH-CX-DG formula.

scholarly journals Network Pharmacological Analysis of Huanglian Jiedu Decoction for Anti- Atherosclerosis

2020 ◽  
Author(s):  
Kerui Wu ◽  
Lu Jiang ◽  
Lanlin Huang ◽  
Yaxing He ◽  
Xia Yan ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Fluid Shear Stress ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Active Ingredients ◽  
Active Components ◽  
Protein Protein Interaction ◽  
Target Regulation

Abstract Objective: We aimed to predict the possible active components,key targets and pathways of Huanglian Jiedu Decoction(HLJDD) for anti-atherosclerosis. Methods: The TCMSP database was searched to obtain the active components and targets of HLJDD, the GeneCards and OMIM databases were searched to obtain related targets of atherosclerosis, and we obtain the intersection targets of them, which are the potential targets of HLJDD for anti-atherosclerosis.Application of Cytoscape 3.6.0 software to build a herbal-active ingredient-potential target regulation network.We perform protein-protein interaction(PPI) network analysis of potential targets through STRING 11.0 database and obtain the key targets,and the results of PPI network of key targets were visualized by Cytoscape3.6.0 software. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the key targets were performed using STRING11.0 database, and we finally constructed the possible pharmacological network of HLJDD for anti-atherosclerosis .Results: We finally obtained 14 key active ingredients of HLJDD, 65 key targets of anti-atherosclerosis, and 14 key active ingredients corresponded to 52 of these targets. These targets are mainly involved in biological processes such as reaction to organic substance, reaction to chemical stimulation,etc.They mainly involved in biological signaling pathways such as pathways in cancer,IL-17 signaling pathway,etc. Conclusion: HLJDD may act on 52 key targets such as PTGS2, HSP90AA1 and RELA through 14 key active ingredients, and influence the signaling pathways including fluid shear stress and atherosclerosis,PI3K-Akt signaling pathway,IL-17 signaling pathway,AGE-RAGE signaling pathway in diabetic complications,TNF signaling pathway,etc.Thus, it may play an anti-atherosclerosis role by inhibiting inflammatory reaction, oxidative stress and improving hemodynamics,etc.

scholarly journals The Mechanism of Aidi Injection on Breast Cancer Based on Network Pharmacologyanalysis

2020 ◽  
Author(s):  
Jing Su ◽  
Kedi Liu ◽  
Xingru Tao ◽  
Fei Li ◽  
Shi Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Bioactive Components ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Pharmacological Mechanism ◽  
Target Network ◽  
Aidi Injection

Abstract Background: Aidi injection (ADI)is a Chinese patent medicine with anti-cancer effect, which has been used to treat breast cancer (BC) in China for many years, but its potential pharmacological mechanism is still indeterminacy. In this resaearch, network pharmacology, a systematic and comprehensive approach, was used to reveal ADI's potential pharmacological mechanism in treating BC for the first time.Methods: Databases were used to collect targets related to the bioactive components of ADI and BC. the relevant networks were established by the string database, and were screened potential bioactive components and core targets. Eventually, core targets and pathway enrichment were analyzed by DAVID database.Results: As the results showed, we collected 99 bioactive ingredients,345 ADI-related targets after deduplication and 368 BC-related targets. Of these, 108 common targets were overlapped. We then performed an enrichment analysis on the common target network and the protein-protein interaction (PPI) network.Conclusion: The results showed that ADI may inhibit breast cancer through seven important signal pathways involved in the "regulation of vascular endothelial function", "inflammatory response" and "apoptosis” biological processes. Through further clustering and enrichment analysis of the PPI network of ADI’s bioactive component targets and BC-related targets, we found that cancer, ErbB, MAPK, TLR, chemokine, p53 and cell cycle signaling pathway, mainly contributed to the effects of ADI in treating BC. In conclusion, this study reveals the possible mechanism of ADI in treating BC, and provides a new direction for drug development for ADI in treating BC.

scholarly journals Exploring the Pharmacological Mechanism of Quercetin-Resveratrol Combination for Polycystic Ovary Syndrome: A Systematic Pharmacological Strategy-Based Research

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Tingting Bao ◽  
Zhiyong Long ◽  
Bing Jin
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Molecular Mechanism ◽  
Polycystic Ovary ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Ppi Network ◽  
Ovary Syndrome ◽  
Potential Target ◽  
Target Network ◽  
Compound Target

AbstractResveratrol and quercetin have effects on polycystic ovary syndrome (PCOS). Hence, resveratrol combined with quercetin may have better effects on it. However, because of the limitations in animal and human experiments, the pharmacological and molecular mechanism of quercetin-resveratrol combination (QRC) remains to be clarified. In this research, a systematic pharmacological approach comprising multiple compound target collection, multiple potential target prediction, and network analysis was used for comparing the characteristic of resveratrol, quercetin and QRC, and exploring the mechanism of QRC. After that, four networks were constructed and analyzed: (1) compound-compound target network; (2) compound-potential target network; (3) QRC-PCOS PPI network; (4) QRC-PCOS-other human proteins (protein-protein interaction) PPI network. Through GO and pathway enrichment analysis, it can be found that three compounds focus on different biological processes and pathways; and it seems that QRC combines the characteristics of resveratrol and quercetin. The in-depth study of QRC further showed  more PCOS-related biological processes and pathways. Hence, this research not only offers clues to the researcher who is interested in comparing the differences among resveratrol, quercetin and QRC, but also provides hints for the researcher who wants to explore QRC’s various synergies and its pharmacological and molecular mechanism.

scholarly journals Network pharmacology study of vaccarin for the prevention and treatment of postmenopausal osteoporosis

2020 ◽  
Author(s):  
Mengying Bao ◽  
Yan Dai ◽  
Xiaojun Chen ◽  
Shijie Liao ◽  
Wenyu Feng ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Postmenopausal Osteoporosis ◽  
Inflammatory Responses ◽  
Enrichment Analysis ◽  
Osteoclast Formation ◽  
Flavonoid Glycoside ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Ppi Network ◽  
Prevention And Treatment

Abstract Background: As the main active ingredient of Semen Vaccariae, vaccarin is a flavonoid glycoside useful for the prevention and treatment of numerous diseases. Our previous study found that vaccarin can reduce osteolysis-induced titanium by inhibiting osteoclast formation. However, the issue of whether vaccarin can prevent and treat postmenopausal osteoporosis remains unclear.Method: In this study, we explored the mechanism of action of vaccarin for the prevention of postmenopausal osteoporosis via a network pharmacological approach. We identified the intersecting targets of osteoporosis-related genes retrieved from multiple disease target databases, as well as targets of potential action of vaccarin retrieved from drug-related databases. We then used the intersectional targets to establish a protein-protein interaction (PPI) network. Finally, we performed bioinformatics analysis to enrich Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.Results：A total of 28 cross targets of vaccarin and osteoporosis were identified. PPI network analysis identified six target proteins, namely, IL-6, TNF, VEGFA, HSP90AA1, CREB1, and IL-2, which may be the key targets of vaccarin against osteoporosis. The 28 intersectional targets were mainly involved in 23 biological processes, such as regulation of apoptosis, positive regulation of neovascularization, and angiogenesis, whereas KEGG enrichment analysis revealed that they were primarily related to 22 different signaling pathways, such as PI3K/Akt pathway, cancer pathway, hepatitis B pathway, and tuberculosis pathway.Conclusion: We used a network pharmacology approach to predict the key targets of vaccarin for the prevention of osteoporosis from a systems perspective. We determined that the signaling pathways were chiefly engaged in different pathological processes affecting differentiation and apoptosis of bone rebuilding cells, endocrine metabolic disorders, inflammatory responses, and other disease interactions. This study provides a theoretical basis and therapeutic ideas for the treatment of postmenopausal osteoporosis and offers promising directions for further research on the regulatory mechanism of vaccarin.

scholarly journals Melittin Constrains the Expression of Identified Key Genes Associated with Bladder Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Zidan Jin ◽  
Jie Yao ◽  
Nianlin Xie ◽  
Libo Cai ◽  
Shuai Qi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Signaling Pathways ◽  
Theoretical Basis ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Pcr Analysis ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Pubmed Database ◽  
Key Genes

This work is aimed at investigating the effect of melittin on identified key genes in bladder cancer (BC) and further providing a theoretical basis for BC treatment. GSE35014 downloaded from the Gene Expression Omnibus (GEO) database was used to screen differentially expressed genes (DEGs) in BC cells and control. Results showed that a total of 389 upregulated and 169 downregulated genes were identified. Subsequently, GO analysis, KEGG pathway enrichment analysis, and PPI network analysis were employed to disclose the crucial genes and signaling pathways involved in BC. Fifteen module-related DEGs and their associated signaling pathways were obtained according to the PPI network and modular analyses. Based on the analysis of articles retrieved in the PubMed database, we found that melittin could induce apoptosis and constrain the progression of tumor cells as a result of regulating critical cancer-related signaling pathways, such as PI3K-Akt and TNF signaling pathways. Furthermore, PI3K-Akt and TNF signaling pathways were also found to be associated with module-related DEGs according to biological analyses. At last, qRT-PCR analysis demonstrated that melittin could constrain the expression of module-related DEGs (LPAR1, COL5A1, COL6A2, CXCL1, CXCL2, and CXCL3) associated with PI3K-Akt and TNF signaling pathways in BC cells. Functional assays revealed that melittin could constrain the proliferative and migrated abilities of BC cells. Conjointly, these findings provide a theoretical basis for these six genes as drug-sensitive markers of melittin in BC treatment.

scholarly journals Network Pharmacology Strategy to Investigate the Pharmacological Mechanism of HuangQiXiXin Decoction on Cough Variant Asthma and Evidence-Based Medicine Approach Validation

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Qingqing Xia ◽  
Mingtao Liu ◽  
Hui Li ◽  
Lijun Tian ◽  
Jia Qi ◽  
...  
Keyword(s):  
Target Genes ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Curative Effect ◽  
Cough Variant Asthma ◽  
Related Target ◽  
Active Target ◽  
Pharmacological Mechanism ◽  
Target Network

Objective. To investigate the pharmacological mechanism of HuangQiXiXin decoction (HQXXD) on cough variant asthma (CVA) and validate the clinical curative effect. Methods. The active compounds and target genes of HQXXD were searched using TCMSP. CVA-related target genes were obtained using the GeneCards database. The active target genes of HQXXD were compared with the CVA-related target genes to identify candidate target genes of HQXXD acting on CVA. A medicine-compound-target network was constructed using Cytoscape 3.6.0 software, and a protein-protein interaction (PPI) network was constructed using the STRING database. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using RGUI3.6.1 and Cytoscape 3.6.0. We searched the main database for randomized controlled trials of HQXXD for CVA. We assessed the quality of the included studies using the Cochrane Reviewers’ Handbook. A meta-analysis of the clinical curative effect of HQXXD for CVA was conducted using the Cochrane Collaboration’s RevMan 5.3 software. Results. We screened out 48 active compounds and 217 active target genes of HQXXD from TCMSP. The 217 active target genes of HQXXD were compared with the 1481 CVA-related target genes, and 132 candidate target genes for HQXXD acting on CVA were identified. The medicine-compound-target network and PPI network were constructed, and the key compounds and key targets were selected. GO function enrichment and KEGG pathway enrichment analysis were performed. Meta-analysis showed that the total effective rate of the clinical curative effect was significantly higher in the experimental group than the control group. Conclusion. The pharmacological mechanism of HQXXD acting on CVA has been further determined, and the clinical curative effect of HQXXD on CVA is remarkable.

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