Paeoniflorin alleviates high glucose-induced endothelial cell apoptosis in diabetes mellitus by inhibiting HRAS-activated RAS pathway
Paeoniflorin (Pae) can improve diabetes mellitus (DM), especially endothelial dysfunction induced by high glucose (HG). Molecularly, the mechanism pertinent to Pae and DM lacks further in-depth research. Hence, this study determined the molecular mechanism of Pae in treating DM through network pharm...
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The Japan Endocrine Society
2024-11-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/11/71_EJ24-0122/_html/-char/en |
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| author | Wenting Yu Hongchun Jiang |
| author_facet | Wenting Yu Hongchun Jiang |
| author_sort | Wenting Yu |
| collection | DOAJ |
| description | Paeoniflorin (Pae) can improve diabetes mellitus (DM), especially endothelial dysfunction induced by high glucose (HG). Molecularly, the mechanism pertinent to Pae and DM lacks further in-depth research. Hence, this study determined the molecular mechanism of Pae in treating DM through network pharmacology. The target of Pae was analyzed by TCMSP database, and DM-related genes were dissected by Genecards database and Omim database. PPI network was constructed for cross targets through Cytoscape 3.9.1 and STRING platform. GO and KEGG analyses were carried out on the cross targets. Protein molecular docking verification was completed by AutoDockTools and Pymol programs. Human umbilical vein endothelial cells (HUVECs) were separately treated with HG, Pae (5, 10, 20 μM) and/or HRAS overexpression plasmids (oe-HRAS). The cell viability, apoptosis and the protein expressions of HRAS and Ras-GTP were evaluated. There were 50 cross targets between Pae and DM, and VEGFA, EGFR, HRAS, SRC and HSP90AA1 were the key genes identified by PPI network analysis. GO and KEGG analyses revealed signal paths such as Rap1 and Ras. Molecular docking results confirmed that Pae had a good binding ability with key genes. In HG-treated HUVECs, Pae dose-dependently facilitated cell viability, attenuated cell apoptosis, and dwindled the expressions of HRAS and Ras-GTP, but these effects of Pae were reversed by oe-HRAS. In conclusion, Pae regulates the viability and apoptosis of HG-treated HUVECs by inhibiting the expression of HRAS. |
| format | Article |
| id | doaj-art-b3c7cba6e828401da36746498e9621ac |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-b3c7cba6e828401da36746498e9621ac2025-01-22T05:38:18ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-11-0171111045105310.1507/endocrj.EJ24-0122endocrjPaeoniflorin alleviates high glucose-induced endothelial cell apoptosis in diabetes mellitus by inhibiting HRAS-activated RAS pathwayWenting Yu0Hongchun Jiang1Department of Infection Control, Red Flag Hospital Affiliated to Mudanjiang Medical College, Heilongjiang 157011, ChinaThe Third Department of Ophthalmology, Mudanjiang Medical College Affiliated Hongqi Hospital First Branch, Heilongjiang 157099, ChinaPaeoniflorin (Pae) can improve diabetes mellitus (DM), especially endothelial dysfunction induced by high glucose (HG). Molecularly, the mechanism pertinent to Pae and DM lacks further in-depth research. Hence, this study determined the molecular mechanism of Pae in treating DM through network pharmacology. The target of Pae was analyzed by TCMSP database, and DM-related genes were dissected by Genecards database and Omim database. PPI network was constructed for cross targets through Cytoscape 3.9.1 and STRING platform. GO and KEGG analyses were carried out on the cross targets. Protein molecular docking verification was completed by AutoDockTools and Pymol programs. Human umbilical vein endothelial cells (HUVECs) were separately treated with HG, Pae (5, 10, 20 μM) and/or HRAS overexpression plasmids (oe-HRAS). The cell viability, apoptosis and the protein expressions of HRAS and Ras-GTP were evaluated. There were 50 cross targets between Pae and DM, and VEGFA, EGFR, HRAS, SRC and HSP90AA1 were the key genes identified by PPI network analysis. GO and KEGG analyses revealed signal paths such as Rap1 and Ras. Molecular docking results confirmed that Pae had a good binding ability with key genes. In HG-treated HUVECs, Pae dose-dependently facilitated cell viability, attenuated cell apoptosis, and dwindled the expressions of HRAS and Ras-GTP, but these effects of Pae were reversed by oe-HRAS. In conclusion, Pae regulates the viability and apoptosis of HG-treated HUVECs by inhibiting the expression of HRAS.https://www.jstage.jst.go.jp/article/endocrj/71/11/71_EJ24-0122/_html/-char/endiabetes mellitusendothelial dysfunctionpaeoniflorinhras |
| spellingShingle | Wenting Yu Hongchun Jiang Paeoniflorin alleviates high glucose-induced endothelial cell apoptosis in diabetes mellitus by inhibiting HRAS-activated RAS pathway Endocrine Journal diabetes mellitus endothelial dysfunction paeoniflorin hras |
| title | Paeoniflorin alleviates high glucose-induced endothelial cell apoptosis in diabetes mellitus by inhibiting HRAS-activated RAS pathway |
| title_full | Paeoniflorin alleviates high glucose-induced endothelial cell apoptosis in diabetes mellitus by inhibiting HRAS-activated RAS pathway |
| title_fullStr | Paeoniflorin alleviates high glucose-induced endothelial cell apoptosis in diabetes mellitus by inhibiting HRAS-activated RAS pathway |
| title_full_unstemmed | Paeoniflorin alleviates high glucose-induced endothelial cell apoptosis in diabetes mellitus by inhibiting HRAS-activated RAS pathway |
| title_short | Paeoniflorin alleviates high glucose-induced endothelial cell apoptosis in diabetes mellitus by inhibiting HRAS-activated RAS pathway |
| title_sort | paeoniflorin alleviates high glucose induced endothelial cell apoptosis in diabetes mellitus by inhibiting hras activated ras pathway |
| topic | diabetes mellitus endothelial dysfunction paeoniflorin hras |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/11/71_EJ24-0122/_html/-char/en |
| work_keys_str_mv | AT wentingyu paeoniflorinalleviateshighglucoseinducedendothelialcellapoptosisindiabetesmellitusbyinhibitinghrasactivatedraspathway AT hongchunjiang paeoniflorinalleviateshighglucoseinducedendothelialcellapoptosisindiabetesmellitusbyinhibitinghrasactivatedraspathway |