Molecular Biological Mechanism ofBletilla striata on Neuropsychiatric System by Network Pharmacology and Experimental Validation

2021 ◽  
Vol 15 (5) ◽  
pp. 663-670
Author(s):  
Jun Li ◽  
Shirun Chu ◽  
Mei Yang ◽  
Jungang Yue ◽  
Lu Wang ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Functional Groups ◽  
Cell Activity ◽  
Neuronal Cell ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Bletilla Striata ◽  
Material Basis ◽  
Neuropsychiatric Diseases

Bletilla striata is a rare traditional Chinese medicine with protective effect for neuropsychiatric system. Nevertheless, the material basis and molecular mechanism of this effect remain unclear. By means of network pharmacology, five common neuropsychiatric targets for B. striata ingredients that can pass through the blood-brain barrier were conducted to probe the material basis and molecular mechanism of its neuropsychiatric protecting effects. Besides, the in vitro model of neurons injury was built to verify the effect of these ingredients on neurons. Results indicated that 8 active ingredients and 21 core targets were screened, and 9 groups of gene functional groups were screened by GO analysis. The KEGG pathway enrichment revealed that, 14 signal pathways were mapped and 6 REACTOME Pathways and 33 Wiki Pathways were also detected. Preliminary experimental verification demonstrated that, B. striata protected, maintained and enhanced neuronal cell activity and up-regulated the expression of DRD2 and GRM2 genes through dihydrophenanthrene compounds. From the above results, we speculated that B. striata may act on multi-target gene functional groups through multiple ingredients, resulting in various effects, thus achieving the purpose of protecting the neuropsychiatric system, as well as its functions. Our research findings also suggested that the experimental research method combining network pharmacology with experimental cell research is effective for quickly analyzing the material basis and molecular mechanism of B. striata in protecting the neuropsychiatric system and treating neuropsychiatric diseases.

scholarly journals Molecular mechanism underlying the hypolipidemic effect of Shanmei Capsule based on network pharmacology and molecular docking

2021 ◽  
Vol 29 ◽  
pp. 239-256
Author(s):  
Qian Wang ◽  
Lijing Du ◽  
Jiana Hong ◽  
Zhenlin Chen ◽  
Huijian Liu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Kegg Pathway ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Signal Pathways ◽  
Hypolipidemic Effect ◽  
Active Ingredients ◽  
Pathway Enrichment

BACKGROUND: Shanmei Capsule is a famous preparation in China. However, the related mechanism of Shanmei Capsule against hyperlipidemia has yet to be revealed. OBJECTIVE: To elucidate underlying mechanism of Shanmei Capsule against hyperlipidemia through network pharmacology approach and molecular docking. METHODS: Active ingredients, targets of Shanmei Capsule as well as targets for hyperlipidemia were screened based on database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed via Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8 database. Ingredient-target-disease-pathway network was visualized utilizing Cytoscape software and molecular docking was performed by Autodock Vina. RESULTS: Seventeen active ingredients in Shanmei Capsule were screened out with a closely connection with 34 hyperlipidemia-related targets. GO analysis revealed 40 biological processes, 5 cellular components and 29 molecular functions. A total of 15 signal pathways were enriched by KEGG pathway enrichment analysis. The docking results indicated that the binding activities of key ingredients for PPAR-α are equivalent to that of the positive drug lifibrate. CONCLUSIONS: The possible molecular mechanism mainly involved PPAR signaling pathway, Bile secretion and TNF signaling pathway via acting on MAPK8, PPARγ, MMP9, PPARα, FABP4 and NOS2 targets.

Insight into the molecular mechanism of a herbal injection by integrating network pharmacology and in vitro

2015 ◽  
Vol 173 ◽  
pp. 91-99 ◽  
Author(s):  
Yi-min Ma ◽  
Xin-zhuang Zhang ◽  
Zhen-zhen Su ◽  
Na Li ◽  
Liang Cao ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Network Pharmacology ◽  
Insight Into

scholarly journals Chlorogenic acid protects PC12 cells against corticosterone-induced neurotoxicity related to inhibition of autophagy and apoptosis

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaowen Shi ◽  
Nian Zhou ◽  
Jieyi Cheng ◽  
Xunlong Shi ◽  
Hai Huang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Chlorogenic Acid ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Molecular Mechanism ◽  
Cell Activity ◽  
Neuronal Cell ◽  
Mtor Signaling ◽  
Specific Marker ◽  
Mtor Signaling Pathway

Abstract Background There are evidences that chlorogenic acid (CGA) has antidepressant effects, however the underlying molecular mechanism has not been well understood. The aim of the study was to explore the neuroprotective effect of CGA on corticosterone (CORT)-induced PC 12 cells and its mechanism, especially the autophagy pathway. Methods PC12 cells were incubated with CORT (0, 100, 200, 400 or 800 μM) for 24 h, cell viability was measured by MTT assay. PC12 cells were cultured with 400 μM of CORT in the absence or presence of CGA (25 μg/ml) for 24 h, morphologies and specific marker of autophagosome were observed by transmission electron microscope (TEM) and confocal immunofluorescence microscopy, respectively. In addition, PC12 cells were treated with different doses of CGA (0, 6.25, 12.5, 25 or 50 μg/ml) with or without CORT (400 μM) for 24 h, cell viability and changes in the morphology were observed, and further analysis of apoptotic and autophagic proteins, and expression of AKT/mTOR signaling pathway were carried out by Western blot. Specific inhibitors of autophagy 3-Methyladenine (3-MA) and chloroquine (CQ) were added to the PC12 cells cultures to explore the potential role of autophagy in CORT-induced neuronal cell apoptosis. Results Besides decreasing PC12 cell activity, CORT could also induce autophagy and apoptosis of PC12 cells, while CGA could reverse these effects. In addition, CGA treatment regulated AKT/mTOR signaling pathway in PC12 cells. CGA, similar to 3-MA and QC, significantly inhibited CORT-induced apoptosis in PC12 cells. Conclusions Our results provide a new molecular mechanism for the treatment of CORT-induced neurotoxicity by CGA, and suggest CGA may be a potential substance which is can alleviate depression.

scholarly journals Molecular mechanism of the anti-lung cancer effect of Jin Ning Fang based on network pharmacology and experimental verification

2021 ◽  
Author(s):  
Chunxiao Wu ◽  
Qiquan Yu ◽  
Weizhen Shou ◽  
Kun Zhang ◽  
Yang Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Mechanism ◽  
Mrna Level ◽  
A549 Cells ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Apoptosis Pathway ◽  
Protein Protein Interaction ◽  
Anti Cancer

Background: Jin Ning Fang (JNF) is widely used as an adjuvant therapy for lung cancer. However, its molecular mechanism against lung cancer is still unclear. Methods: The chemical compounds JNF were screened from the TCMSP database and its target proteins were then predicted. The genes related to lung cancer were collected from the CTD and DisGeNET databases. Next, targets were integrated with disease-related genes to obtain candidate genes. Functional enrichment and protein-protein interaction (PPI) analysis were also performed, followed by construction of pharmacological network. Meanwhile, Autodock was used to assess the affinity between targets and compound. Finally, the anti-cancer effect of JNF on lung cancer cells was detected and some predicted key genes was validated by using real-time PCR. Results: Twenty-five overlapping targets were obtained, and pathway analysis showed that JNF might exert its anti-cancer function by regulating some biological pathways, such as apoptosis pathway. PPI and pharmacological network revealed several core targets (such as AKT1, AR, and ESR1) and three compounds (quercetin, calcium carbonate, and beta-sitosterol). Then, beta-sitosterol had a high affinity with AKT1, AR, and ESR1. Further in vitro experiments confirmed that JNF could inhibit proliferation and promote apoptosis of A549 cells. The expression of FDPS, PIM1, VCAM1, SLC29A1, NQO1, and ESR1 were significantly decreased, while mRNA level of AR and ANPEP were markedly increased after JNF treatment. Conclusion: JNF may exert anti-lung cancer effect through multiple targets and pathways, and identified genes may be used as potential biomarkers for diagnosis and treatment of lung cancer.

scholarly journals Mechanism of Youguiyin in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Yi Pan ◽  
Wanlu Zhao ◽  
Luping Qin ◽  
Lu Zhang
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Transcriptional Gene Silencing ◽  
Pathway Enrichment Analysis ◽  
Signal Pathways ◽  
Biological Processes ◽  
The Core ◽  
Material Basis

Abstract Background: Youguiyin (YGY) has been confirmed to treat osteoporosis (OP) in clinical trials, but its specific pharmacological mechanism remains unclear. This study aimed to explore the material basis and potential mechanism of YGY in the treatment of OP based on network pharmacology and molecular docking.Methods: Databases including TCMSP, SwissTargetPrediction database, OMIM, and TTD were used to predict the effective ingredients and relevant targets of YGY in the treatment of OP. The STRING database was used to reveal the relationship between each intersection target protein. Metascape database was used to perform GO enrichment analysis and KEGG pathway enrichment analysis on the intersection targets. Cytoscape 3.6.0 software was used to show the complex network relationship of YGY in the treatment of OP. According to the results of network characteristics analysis, the core effective ingredients and the core targets were screened out. Autodock 4.0 was used for molecular docking and Pymol was used to visualize the docking results.Results: 290 effective ingredients, 1127 targets of the effective ingredients, 273 relevant targets of OP and 17 intersection targets were screened out in total by searching literature and databases. Intersection targets could affect biological processes including regulation of inflammatory response, ossification, negative regulation of post-transcriptional gene silencing, positive regulation of cytokine biosynthetic process and regulation of hormone levels by regulating signal pathways including TNF signaling pathway, osteoclast differentiation, apoptosis, MAPK signaling pathway and PI3K/Akt signaling pathway. Through screening, 14 core effective ingredients and 6 core targets were confirmed. The results of molecular docking showed that most of the core effective ingredients including α-humulene, cinnamaldehyde, denudatine, benzoylhypaconine and quercetin had good binding activity with the core targets including TNF-α, IL-1β and IL-6.Conclusion: Based on network pharmacology and molecular docking, the critical effective ingredients, key targets, important signal pathways and main biological processes of YGY in the treatment of OP were successfully screened out. This study revealed the material basis and the mechanism of YGY in the treatment of OP and provided a theoretical basis for follow-up experimental research and clinical application of YGY.

scholarly journals Exploration of the Potential Mechanism of Tao Hong Si Wu Decoction for the Treatment of Breast Cancer Based on Network Pharmacology and In Vitro Experimental Verification

2021 ◽  
Vol 11 ◽  
Author(s):  
Shi Huang ◽  
Yan Chen ◽  
Lingyu Pan ◽  
Changyi Fei ◽  
Ni Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Potential Mechanism ◽  
Active Ingredients ◽  
The Core

BackgroundTao Hong Si Wu Decoction (THSWD) is a well-known traditional Chinese medicine used clinically alone or combined with drugs to treat breast cancer. However, there has been no study to date on the underlying mechanisms of its therapeutic effects.ObjectivesTo explore the potential mechanism of THSWD for the treatment of breast cancer using network pharmacology and experimental research.MethodsThe active ingredients of THSWD were screened according to Lipinski’s rule of five based on the 107 ingredients of THSWD identified by UPLC-Q-TOF-MSE. The targets of THSWD and breast cancer from multiple databases were collected, and a Compound-Target-Pathway network based on protein-protein interaction (PPI) was constructed. Gene ontology (GO) analysis and KEGG pathway analysis were performed via the DAVID server. Molecular docking studies verified the selected key ingredients and key targets. The results of network pharmacology were verified by in vitro experiments. Including the effects of THSWD drug-containing rat serum (THSWD serum) on cell proliferation, and on the targets HRAS, MAPK1, AKT1, GRB2, and MAPK14 were assayed by RT-qPCR and Western blot assays.ResultsIn total, 27 active ingredients including 8 core components, were obtained from 107 ingredients and 218 THSWD target genes for the treatment of breast cancer were identified. THSWD is active in the treatment of breast cancer by targeting Ras, FoxO, PI3K-Akt and other signaling pathways. MCF-7 and MDA-MB-231 cell proliferation was inhibited by THSWD serum in a time and concentration dependent manner. THSWD could regulated the RNA and protein expression of core targets HRAS, MAPK1, AKT1, GRB2, and MAPK14 for treatment of breast cancer.ConclusionThe results of network pharmacology study showed that THSWD is active against breast cancer by intervening with multiple targets and pathways. Luteolin, kaempferol, senkyunolide E, and other 8 compounds may be the core active ingredients of THSWD in the treatment of breast cancer. THSWD treatment of breast cancer may be related to targeting Ras, FoxO, PI3K-Akt, and other signal pathways associated with the core targets HRAS, MAPK1, AKT1, GRB2, and MAPK14.

scholarly journals Mechanism of Youguiyin In The Treatment of Osteoporosis Based On Network Pharmacology And Molecular Docking

2021 ◽  
Author(s):  
Yi Pan ◽  
Wanlu Zhao ◽  
Luping Qin ◽  
Lu Zhang
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Transcriptional Gene Silencing ◽  
Pathway Enrichment Analysis ◽  
Signal Pathways ◽  
Biological Processes ◽  
The Core ◽  
Material Basis

Abstract Background: Youguiyin (YGY) has been confirmed to treat osteoporosis (OP) in clinical trials, but its specific pharmacological mechanism remains unclear. This study aimed to explore the material basis and potential mechanism of YGY in the treatment of OP based on network pharmacology and molecular docking.Methods: Databases including TCMSP, SwissTargetPrediction database, OMIM, and TTD were used to predict the effective ingredients and relevant targets of YGY in the treatment of OP. The STRING database was used to reveal the relationship between each intersection target protein. Metascape database was used to perform GO enrichment analysis and KEGG pathway enrichment analysis on the intersection targets. Cytoscape 3.6.0 software was used to show the complex network relationship of YGY in the treatment of OP. According to the results of network characteristics analysis, the core effective ingredients and the core targets were screened out. Autodock 4.0 was used for molecular docking and Pymol was used to visualize the docking results.Results: 290 effective ingredients, 1127 targets of the effective ingredients, 273 relevant targets of OP and 17 intersection targets were screened out in total by searching literature and databases. Intersection targets could affect biological processes including regulation of inflammatory response, ossification, negative regulation of post-transcriptional gene silencing, positive regulation of cytokine biosynthetic process and regulation of hormone levels by regulating signal pathways including TNF signaling pathway, osteoclast differentiation, apoptosis, MAPK signaling pathway and PI3K/Akt signaling pathway. Through screening, 14 core effective ingredients and 6 core targets were confirmed. The results of molecular docking showed that most of the core effective ingredients including α-humulene, cinnamaldehyde, denudatine, benzoylhypaconine and quercetin had good binding activity with the core targets including TNF-α, IL-1β and IL-6.Conclusion: Based on network pharmacology and molecular docking, the critical effective ingredients, key targets, important signal pathways and main biological processes of YGY in the treatment of OP were successfully screened out. This study revealed the material basis and the mechanism of YGY in the treatment of OP and provided a theoretical basis for follow-up experimental research and clinical application of YGY.

Study on the Mechanism of Paeoniflorin Against Atherosclerosis Through Network Pharmacology and Molecular Docking

2020 ◽  
Vol 14 (4) ◽  
pp. 467-475
Author(s):  
Chengguo Zhao ◽  
Wenpei Ling ◽  
Chunyu Luo ◽  
Meifang Yin ◽  
Shuzhi Qin
Keyword(s):  
Molecular Docking ◽  
Protein Modification ◽  
Cell Activity ◽  
Enrichment Analysis ◽  
Binding Activity ◽  
Signalling Pathway ◽  
Network Pharmacology ◽  
Literature Mining ◽  
Signal Pathways ◽  
Cyclic Compounds

This study explored the mechanism of paeoniflorin (PF) against atherosclerosis (AS) at the molecular level using network pharmacology and molecular docking. The targets of PF and disease targets related to AS were obtained through literature mining and database search, the PPI network diagram was drawn, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the PF structure was docked with core target. In the results, 130 common target proteins of PF and AS were obtained. GO enrichment analysis found 1071 items related to biological processes, mainly related to metabolism, protein modification, regulation of cell activity, regulation of macromolecule synthesis, etc. There were 107 items related to molecular functions, mainly related to cyclic compounds, ions, nucleotides, and ribose Combine etc. KEGG analysis revealed 79 pathways, mainly Pathways in cancer, PI3K-Akt signalling pathway, Proteoglycans in cancer, Ras signalling pathway, FoxO signalling pathway, etc. The molecular docking results showed that PF had good binding activity with the screened target. In conclusion, this study indicated that PF treatment of AS involves multiple direct or indirect targets and signal pathways, providing a reference for further research on the mechanism of PF treatment of AS.

scholarly journals Regulatory Mechanism and Experimental Verification of Patchouli Alcohol on Gastric Cancer Cell Based on Network Pharmacology

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanru Song ◽  
Liang Chang ◽  
Xiaoyuan Wang ◽  
Bibo Tan ◽  
Jianbo Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanism ◽  
Gastrointestinal Diseases ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Patchouli Alcohol ◽  
Pogostemon Cablin ◽  
The Impact

BackgroundPogostemon cablin is a traditional Chinese medicine (TCM) that is frequently used to treat various gastrointestinal diseases. Patchouli alcohol (PA), a compound extracted from the Pogostemon cablin, has been shown to have anti-tumor efficacy in human colorectal cancer. However, the mechanism of PA’s anticancer effect on gastric cancer (GC) remains unknown.MethodsWe used the public database to obtain the potential targets of PA and genes related to GC. Bioinformatic analyses, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interactions (PPI), were used for analyzing the potential signal pathways and targets. Cell experiments were also conducted to further explain the impact and molecular mechanism of PA on GC, as well as to confirm the findings of network pharmacology.ResultsUsing network pharmacological analysis, 161 possible targets were identified for the treatment of GC. Network analysis and functional enrichment analysis show that PA produced a marked effect in the treatment of GC through multi-targets and multi-pathways, especially the MAPK and PI3K/AKT signal pathways. In addition, PA showed the inhibition of GC cell proliferation, migration and invasion in cell experiments. According to our findings, PA could also cause G0/G1 phase arrest and apoptosis in GC cells.ConclusionUsing network pharmacology, we aim to uncover the possible molecular mechanism of PA on GC treatment in this research. Cell experiments were also conducted to confirm the therapeutic effect of PA on GC.

scholarly journals Potential molecular mechanism of Yishen capsule in the treatment of diabetic nephropathy based on network pharmacology and molecular docking technology

2021 ◽  
Author(s):  
Yaling Hu ◽  
Shuang Liu ◽  
Wenyuan Liu ◽  
Ziyuan Zhang ◽  
Yuxiang Liu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Docking ◽  
Signaling Pathways ◽  
High Glucose ◽  
Kidney Tissue ◽  
Signal Pathway ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Active Components

Abstract Background : Using network pharmacology and molecular docking technology to explore the mechanism of Yishen capsules in the treatment of diabetic nephropathy. Methods: Active components of Yishen Capsules were obtained using database such as TCMSP and TCMID, and diabetic nephropathy targets were obtained from databases such as Gencards, OMIM, DisGeNET. A network of "Yishen Capsule Components-Diabetic Nephropathy Targets-Pathways" was constructed by analyzing data above to screening out core targets for molecular docking verification. Finally, a rat model of diabetic nephropathy was generated, and renal tubular epithelial cells were extracted and cultured under high glucose conditions. Based on these experimental models, the key signal pathway target protein genes screened by network pharmacology were verified both in vitro and in vivo. Results: The main active components of Yishen Capsule in the treatment of diabetic nephropathy include quercetin, kaempferol, gallic acid, astragaloside IV and so on. Some key targets (such as AR, AKT1, TP53, ESR1, JUN) and important signal pathways (such as AGE-RAGE signal pathway, HIF-1 signal pathway and JAK-STAT signal pathway) were included in the treatment of diabetic nephropathy of Yishen Capsule. Molecular docking assay showed that most of the targets have good binding activity with the components of Yishen Capsules. Based on the results of network pharmacology, key target proteins in HIF-1α and JAK2/STAT3 signaling pathways were selected for experimental verification. Results presented that HIF-1α, JAK2, STAT3, TGF-β and MCP were increased under high glucose environment. With the treatment of Yishen Capsule, the expression of HIF-1α further increased, while the expression of JAK2, STAT3, MCP-1 and TGF-β were decreased. Conclusions : This study revealed the mechanism of Yishen Capsules in the treatment of diabetic nephropathy, which possesses the characteristics of multi-component, multi-target, and multi-pathway. Further experiments confirmed that Yishen Capsules interfered with HIF-1α and JAK/STAT signaling pathways to reduce inflammation and fibrosis damage in the kidney tissue of rats with diabetic nephropathy. Key Words: Diabetic Nephropathy(DN); Network pharmacology; Molecular docking;HIF-1α; JAK/STAT

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