Integrating network pharmacology deciphers the action mechanism of Zuojin capsule in suppressing colorectal cancer

Fan, Jinjiang; Xu, Min; Zhou, Liming; Gui, Zhengwei; Li, Xuegang; Ye, Xiaoli

doi:10.1016/j.phymed.2021.153881

Cited by 26 publications

(12 citation statements)

References 34 publications

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“…P21 (encoded by CDKN1A), is a cyclin-dependent kinase inhibitor that prevents the phosphorylation of key cyclin-dependent kinase substrates, thereby inhibiting cell cycle progression. MYC is a key proto-oncogene but currently, there are no therapies that directly target MYC ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated network pharmacology and experimental verification to investigate the mechanisms of YYFZBJS against colorectal cancer via CDK1/PI3K/Akt signaling

Zhou

Yang

et al. 2022

Front. Oncol.

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BackgroundColorectal cancer (CRC) is a common digestive tract malignancy with rising incidence and morbidity worldwide during recent years. Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS), a traditional Chinese medicine formula, has showed positive effects against cancers. However, the mechanisms underlying its anticancer effects requires investigation.MethodsInformation on bioactive compounds, potential YYFZBJS targets, and CRC-associated genes, was obtained from public databases. The key targets and ingredients as well their corresponding signaling pathways were identified using bioinformatic approaches, including Kyoto encyclopedia of genes and genomes (KEGG) analyses, gene ontology (GO), and protein–protein interaction (PPI). Subsequently, molecular docking was used to verify the main compounds-targets. Potential YYFZBJS therapeutic effects against CRC were validated in vitro and in vivo.ResultsUsing pharmacological network analysis, 40 YYFZBJS active compounds and 21 potential anti-CRC targets were identified. YYFZBJS was an important regulator of CRC through various targets and signaling pathways, particularly the cell cycle and PI3K/AKT pathway. Additionally, YYFZBJS suppressed the proliferation of CRC cells. Flow cytometry showed that YYFZBJS induced apoptosis and cell cycle arrest in the G2/M phase. Western blotting analysis indicated that YYFZBJS reduced the protein levels of CDK1, p-AKT, and p-PI3K, without altering total PI3K and AKT protein levels. In vivo analysis found that YYFZBJS inhibited tumor growth and PI3K/AKT signaling in a mouse model of CRC.ConclusionAs predicted by network pharmacology and validated by the experimental results, YYFZBJS inhibited proliferation, induced apoptosis and arrested cell cycle progression in CRC by modulating the CDK1/PI3K/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Integrated network pharmacology and experimental verification to investigate the mechanisms of YYFZBJS against colorectal cancer via CDK1/PI3K/Akt signaling

Zhou

Yang

et al. 2022

Front. Oncol.

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“…The PVDF membranes were scanned using a molecular odyssey infrared imaging system (Li-COR Biosciences), and the bands were analysed. Integrated optical density was used to determine the relative protein content, as previously described [ 16 – 18 ].…”

Section: Methodsmentioning

confidence: 99%

Hydroxycamptothecin regulates scar formation of the filtration channel under scleral flap by inhibiting the proliferation of scleral fibroblasts

Liang

Shen

et al. 2023

PLoS ONE

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Background To investigate the inhibitory effect of a hyaluronic acid hydrogel loaded with hydroxycamptothecin (HCPT) on scar formation after filtration surgery in a rabbit model. Methods Scleral fibroblasts were isolated and extracted from rabbits’ eyes. After treatment with different concentrations of HCPT, cytotoxicity was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and proliferation and extent of apoptosis were analysed using flow cytometry. Hydrogels loaded with different dosages of HCPT were prepared and placed under the scleral flap after the filtration surgery. One day, one week, and two weeks after surgery, follicular, conjunctival, corneal, and anterior chamber inflammation and iris and lens changes were observed. Results In vitro, compared with cells not treated with HCPT, cells treated with HCPT had decreased survival rate and proliferation, and the apoptosis level increased with increasing HCPT concentrations (p < 0.05). In vivo, the flattening time of filtering blebs in the three groups treated with different dosages of HCPT hydrogel was delayed. The degrees of oedema, inflammation, and bleeding were similar to those observed in the control group. The HCPT hydrogel effectively downregulated the expression of collagen 1 and 3 and tissue inhibitor of metalloproteinase 2 and upregulated the expression of matrix metalloproteinase 2 in a dose-dependent manner. Conclusions HCPT significantly inhibited the growth of rabbits’ scleral fibroblasts and effectively inhibited scar formation after filtering surgery by accelerating the degradation of extracellular matrix deposition.

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“…In the TCMSP system, Oral bioavailability (OB) and Drug likeness (DL) is the major parameter to evaluate the quality of active ingredients. As recommended in several studies, the ingredients with OB ≥ 30% and DL ≥ 0.18 are considered to have better pharmacologic effects and can be selected as candidate ingredients for the next step [ 18 ]. All the target proteins corresponding to each molecular were also collected from TCMSP and transformed into gene symbols using the UniProt knowledge database ( https://www.uniprot.org/ ).…”

Section: Methodsmentioning

confidence: 99%

Transcriptome sequencing and network pharmacology-based approach to reveal the effect and mechanism of Ji Chuan Jian against Parkinson’s disease

Liu

et al. 2023

BMC Complement Med Ther

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Background Ji Chuan Jian (JCJ), a classic Traditional Chinese Medicine (TCM) formula, has been widely applied in treating Parkinson’s disease (PD) in China, However, the interaction of bioactive compounds from JCJ with the targets involved in PD remains elusive. Methods Based on the transcriptome sequencing and network pharmacology approaches, the chemical compounds of JCJ and gene targets for treating PD were identified. Then, the Protein-protein interaction (PPI) and “Compound-Disease-Target” (C-D-T) network were constructed by using of Cytoscape. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to these target proteins. Finally, AutoDock Vina was used for applying molecular docking. Results In the present study, a total number of 2669 differentially expressed genes (DEGs) were identified between PD and healthy controls using whole transcriptome RNA sequencing. Then, 260 targets of 38 bioactive compounds in JCJ were identified. Of these targets, 47 were considered PD-related targets. Based on the PPI degree, the top 10 targets were identified. In C-D-T network analysis, the most important anti-PD bioactive compounds in JCJ were determined. Molecular docking revealed that potential PD-related targets, matrix metalloproteinases-9 (MMP9) were more stably bound with naringenin, quercetin, baicalein, kaempferol and wogonin. Conclusion Our study preliminarily investigated the bioactive compounds, key targets, and potential molecular mechanism of JCJ against PD. It also provided a promising approach for identifying the bioactive compounds in TCM as well as a scientific basis for further elucidating the mechanism of TCM formulae in treating diseases.

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Integrating network pharmacology deciphers the action mechanism of Zuojin capsule in suppressing colorectal cancer

Cited by 26 publications

References 34 publications

Integrated network pharmacology and experimental verification to investigate the mechanisms of YYFZBJS against colorectal cancer via CDK1/PI3K/Akt signaling

Integrated network pharmacology and experimental verification to investigate the mechanisms of YYFZBJS against colorectal cancer via CDK1/PI3K/Akt signaling

Hydroxycamptothecin regulates scar formation of the filtration channel under scleral flap by inhibiting the proliferation of scleral fibroblasts

Transcriptome sequencing and network pharmacology-based approach to reveal the effect and mechanism of Ji Chuan Jian against Parkinson’s disease

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