Disclosing targets and pharmacological mechanisms of total bioflavonoids extracted from Selaginella doederleinii against non-small cell lung cancer by combination of network pharmacology and proteomics
| Autor: | Dafen Xu, Ai-Lin Liu, Xinhua Lin, Dan-Dan Huang, Bing Chen, Jianyong Huang, Xuewen Wang |
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| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
Male Proteomics Selaginellaceae Lung Neoplasms MAP Kinase Signaling System Mice Nude Network Pharmacology Mice Western blot In vivo Carcinoma Non-Small-Cell Lung Cell Line Tumor Drug Discovery medicine Animals Humans Epidermal growth factor receptor Protein kinase A Protein kinase B Pharmacology Flavonoids Mice Inbred BALB C biology medicine.diagnostic_test Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays Molecular Docking Simulation Cancer research biology.protein Signal transduction Phosphatidylinositol 3-Kinase Proto-Oncogene Proteins c-akt |
| Zdroj: | Journal of ethnopharmacology. 286 |
| ISSN: | 1872-7573 |
| Popis: | Ethnopharmacological relevance Previously, the total bioflavonoids extract from Selaginella doederleinii (SDTBE) presented favorable in vitro and in vivo activities against non-small cell lung cancer (NSCLC), hinting at its medicinal potential. However, up to nowadays, targets and integrative action mechanisms of SDTBE are still not very clear, which presents an obstacle to the development of herbal medicine. Aim of the study: The present study aimed to disclose the potential targets and integrative action mechanism of SDTBE against NSCLC. Materials and methods A system pharmacology-based strategy including target fishing, network pharmacology analysis and molecular docking were applied to predict the potential targets and pathways for the seven main active ingredients in SDTBE. A proteomics study was subsequently performed for validating the affected pathways and possible targets. Western blot assay, mouse xenograft tumor model and immunofluorescence assays were used to further confirm the key targets and integrative action mechanisms of SDTBE against NSCLC. Results By system pharmacology, it was inferred that SDTBE could mainly act on mitogen-activated protein kinase (MAPK) and PI3K-AKT signaling pathways by targeting epidermal growth factor receptor (EGFR), protein kinase B (AKT) and mitogen-activated or extracellular signal-regulated protein kinase (MEK), which was validated by proteomics results, and further confirmed in vitro and in vivo by Western blot and immunofluorescence assays. Conclusion SDTBE targeting multi-targets including EGFR, AKT and MEK could exert its anti-NSCLC effect mainly via MAPK and PI3K-AKT signaling pathways. |
| Databáze: | OpenAIRE |
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