A network pharmacology strategy to investigate the anti-osteoarthritis mechanism of main lignans components of Schisandrae Fructus
| Autor: | Lingtian Min, Daguo Mi, Yu Wu, Cheng Chen, Gang Cao |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Immunology Cell Network Pharmacology Pharmacology Lignans Mice 03 medical and health sciences 0302 clinical medicine In vivo Osteoarthritis Papain Gene expression medicine Animals Humans Immunology and Allergy Protein Interaction Maps Schisandra Plant Extracts Chemistry Arthritis Experimental In vitro Molecular Docking Simulation Blot 030104 developmental biology medicine.anatomical_structure Fruit 030220 oncology & carcinogenesis Signal transduction Function (biology) Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | International Immunopharmacology. 98:107873 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2021.107873 |
| Popis: | Osteoarthritis (OA) is a chronic age-related progressive joint disorder. Degradation of the cartilage extracellular matrix (ECM) is considered a hallmark of OA and may be a target for new therapeutic methods. Schisandrae Fructus (SF) has been shown to be effective in treating OA. The major active components of SF are lignans. However, the targets of SF and the pharmacological mechanisms underlying the effects of SF lignans in the treatment of OA have not been elucidated. Therefore, based on network pharmacology, this research predicted the treatment targets of six lignans in SF, constructed a protein-protein interaction network and identified 15 hub genes in the OA-target protein-protein interaction network. Through Gene Ontology function and pathway analyses, the gene functions of lignans in the treatment of OA were determined. Finally, the anti-OA effects of lignans and underlying mechanisms identified in the network pharmacology analysis were verified by molecular docking, real-time PCR and western blotting in vitro. The biological processes of the genes and proteins targeted by lignans in the treatment of OA included the immune response, inflammatory response, cell signal transduction and phospholipid metabolism. Moreover, 20 metabolic pathways were enriched. Network pharmacology, molecular docking and in vitro and in vivo experimental results revealed that SF, schisanhenol and gamma-schisandrin inhibited EGFR and MAPK14 gene expression by inhibiting SRC gene expression and activity and then decreased MMP 13 and collagen II protein and gene expression. This research provides a basis for further study of the anti-OA effects and mechanisms of SF, schisanhenol and gamma-schisandrin. |
| Databáze: | OpenAIRE |
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