Investigating the molecular mechanisms of the “Astragalus-Codonopsis” herb pair in treating diabetes: a network pharmacology and bioinformatics approach with molecular docking validation
Astragalus membranaceus and Codonopsis pilosula are widely used in traditional chinese medicine for the treatment of diabetes because of their notable hypoglycemic pharmacological effects. Studies have indicatedthat the active compounds in the Astragalus-Codonopsis herb pair may exert their hypoglyc...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1618575/full |
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| author | Jinliang Yang Mingyang Li Ziyue Zhu Fengling Han Yanyan Ma Jinbo Hou Qingfeng Zhao Hui Yuan XiuMei Li |
| author_facet | Jinliang Yang Mingyang Li Ziyue Zhu Fengling Han Yanyan Ma Jinbo Hou Qingfeng Zhao Hui Yuan XiuMei Li |
| author_sort | Jinliang Yang |
| collection | DOAJ |
| description | Astragalus membranaceus and Codonopsis pilosula are widely used in traditional chinese medicine for the treatment of diabetes because of their notable hypoglycemic pharmacological effects. Studies have indicatedthat the active compounds in the Astragalus-Codonopsis herb pair may exert their hypoglycemic effects through the modulation of the insulin receptor (IRSP) signaling pathway. In this study, the rhamnolitrin and folic acid were confirmed as the key active components in the Astragalus-Codonopsis herb pair that regulate the IRSP, with their synergistic mechanisms in Type 2 Diabetes Mellitus (T2DM) being further systematically explored by network pharmacology combined with DFT theoretical calculation, molecular docking, molecular dynamics simulation and alanine scanning mutation technology. The results suggest that GSK3β is a critical target through which rhamnolitrin and folic acid exert their anti-diabetic effects. Subsequent molecular docking and molecular dynamics simulations confirmed that both active compounds selected in this study can bind stably with the GSK3β protein. Further alanine scanning mutagenesis experiments validated the importance of key amino acid residues in ligand-receptor interactions. Finally, DFT theoretical calculations provided a detailed elucidation of the binding mechanism between the core components (rhamnolitrin and folic acid) and the target protein GSK3β. This study not only revealed the molecular mechanism of Astragalus-Codonopsis for the treatment of type 2 diabetes, provided a theoretical basis for its clinical application, but also provided a potential molecular target for the development of new anti-diabetes drugs. |
| format | Article |
| id | doaj-art-a782310c6b614a849d2ba9846e9c4bbb |
| institution | Kabale University |
| issn | 2296-4185 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj-art-a782310c6b614a849d2ba9846e9c4bbb2025-08-20T03:30:28ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-07-011310.3389/fbioe.2025.16185751618575Investigating the molecular mechanisms of the “Astragalus-Codonopsis” herb pair in treating diabetes: a network pharmacology and bioinformatics approach with molecular docking validationJinliang Yang0Mingyang Li1Ziyue Zhu2Fengling Han3Yanyan Ma4Jinbo Hou5Qingfeng Zhao6Hui Yuan7XiuMei Li8Department of Traditional Chinese Medicine, General Hospital of Ningxia Medical University, Yinchuan, ChinaSchool of Pharmacy, Ningxia Medical University, Yinchuan, ChinaCollege of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaDermatology, Lingwu People’s Hospital, Lingwu, ChinaDermatology, Lingwu People’s Hospital, Lingwu, ChinaSchool of Information Science and Engineering, Henan University of Technology, Zhengzhou, ChinaSchool of Pharmacy, Ningxia Medical University, Yinchuan, ChinaSchool of Pharmacy, Ningxia Medical University, Yinchuan, ChinaSchool of Pharmacy, Ningxia Medical University, Yinchuan, ChinaAstragalus membranaceus and Codonopsis pilosula are widely used in traditional chinese medicine for the treatment of diabetes because of their notable hypoglycemic pharmacological effects. Studies have indicatedthat the active compounds in the Astragalus-Codonopsis herb pair may exert their hypoglycemic effects through the modulation of the insulin receptor (IRSP) signaling pathway. In this study, the rhamnolitrin and folic acid were confirmed as the key active components in the Astragalus-Codonopsis herb pair that regulate the IRSP, with their synergistic mechanisms in Type 2 Diabetes Mellitus (T2DM) being further systematically explored by network pharmacology combined with DFT theoretical calculation, molecular docking, molecular dynamics simulation and alanine scanning mutation technology. The results suggest that GSK3β is a critical target through which rhamnolitrin and folic acid exert their anti-diabetic effects. Subsequent molecular docking and molecular dynamics simulations confirmed that both active compounds selected in this study can bind stably with the GSK3β protein. Further alanine scanning mutagenesis experiments validated the importance of key amino acid residues in ligand-receptor interactions. Finally, DFT theoretical calculations provided a detailed elucidation of the binding mechanism between the core components (rhamnolitrin and folic acid) and the target protein GSK3β. This study not only revealed the molecular mechanism of Astragalus-Codonopsis for the treatment of type 2 diabetes, provided a theoretical basis for its clinical application, but also provided a potential molecular target for the development of new anti-diabetes drugs.https://www.frontiersin.org/articles/10.3389/fbioe.2025.1618575/fullAstragalus-Codonopsisnetwork pharmacologymolecular dynamicsGSK3 βinsulin resistance |
| spellingShingle | Jinliang Yang Mingyang Li Ziyue Zhu Fengling Han Yanyan Ma Jinbo Hou Qingfeng Zhao Hui Yuan XiuMei Li Investigating the molecular mechanisms of the “Astragalus-Codonopsis” herb pair in treating diabetes: a network pharmacology and bioinformatics approach with molecular docking validation Frontiers in Bioengineering and Biotechnology Astragalus-Codonopsis network pharmacology molecular dynamics GSK3 β insulin resistance |
| title | Investigating the molecular mechanisms of the “Astragalus-Codonopsis” herb pair in treating diabetes: a network pharmacology and bioinformatics approach with molecular docking validation |
| title_full | Investigating the molecular mechanisms of the “Astragalus-Codonopsis” herb pair in treating diabetes: a network pharmacology and bioinformatics approach with molecular docking validation |
| title_fullStr | Investigating the molecular mechanisms of the “Astragalus-Codonopsis” herb pair in treating diabetes: a network pharmacology and bioinformatics approach with molecular docking validation |
| title_full_unstemmed | Investigating the molecular mechanisms of the “Astragalus-Codonopsis” herb pair in treating diabetes: a network pharmacology and bioinformatics approach with molecular docking validation |
| title_short | Investigating the molecular mechanisms of the “Astragalus-Codonopsis” herb pair in treating diabetes: a network pharmacology and bioinformatics approach with molecular docking validation |
| title_sort | investigating the molecular mechanisms of the astragalus codonopsis herb pair in treating diabetes a network pharmacology and bioinformatics approach with molecular docking validation |
| topic | Astragalus-Codonopsis network pharmacology molecular dynamics GSK3 β insulin resistance |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1618575/full |
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