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| Exploration of the target mechanism of Rongchang Capsule in the treatment of epilepsy in children based on network pharmacology, molecular docking and molecular dynamics simulation |
| Hits 849 Download times 3906 Received:October 25, 2022 |
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| DOI
10.11656/j.issn.1672-1519.2023.04.16 |
| Key Words
epilepsy;Rongchang Capsule;network pharmacology;molecular docking;molecular dynamics simulation |
| Author Name | Affiliation | E-mail | | AN Zimeng | First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300193, China | | | FU Qianfang | First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300193, China | | | XUE Yaruo | Affiliated Hospital of Nanjing University of traditional Chinese Medicine, Nanjing 210000, China | | | YANG Xinming | First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300193, China | | | GUO Yuning | First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300193, China | | | ZHANG Xilian | First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300193, China | zxl2072@126.com |
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| Abstract
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| [Objective] The team's previous research has confirmed that the treatment of epilepsy by Rongchang Capsules are associated with estrogen levels, autophagy, AMPK, and mTOR signaling pathways, but there is no relationship between components and targets at this time. This paper will use network pharmacology, the multi-molecular, multi-target and multi-pathway mechanism of action of Rongchang Capsule was discussed by docking and molecular dynamics simulation, which provided a reference reference for its basic and clinical research. [Methods] Screening of bioactive components and targets of velvet calamus capsules by TCMSP, TCMID, BATMAN-TCM and literature search, retrieve the disease target information and take the intersection target of drug and disease by GeneCards, OMIM, DisGeNET database;use String database to obtain the protein interaction relationship and use Cytoscape software to construct drug-active ingredient-target maps and drug-target-KEGG network relationship maps;use AutoDockTools, Vina software to perform molecular docking, use Gromacs software to perform molecular dynamics simulations of ESR1 and naringenin. [Results] The 117 active ingredients and 115 drug-disease intersecting targets were screened out of Rongchang Capsules, and 18 core targets were screened by the CytoNCA plug-in. GO analysis showed that it is mainly involved in steroid metabolic process, response to the metal ion, etc. KEGG analysis showed that it was primarily involved in lipid and atherosclerosis pathway, AGE-RAGE, etc. Molecular docking results showd that the Affinity values of 30 pairs of combinations are all ≤ -5(kcal/mol). In molecular dynamics simulation, the values of RMSD and ROG in molecular dynamics simulations fluctuated less, and the values of Res 307-350 and Res 525-551 in RMSF were large. [Conclusion] The potential mechanism of action of Rongchang Capsule in the treatment of epilepsy was predicted by network pharmacology, mainly involving quercetin, kaempferol, β-sitosterol molecule and AKT1, TNF, IL-6 targets, acting on lipid and atherosclerosis pathways, AGE-RAGE signaling pathway, and interleukin-17 signaling pathway to intervention for epilepsy. These pathways are most closely related to neuroinflammation and oxidative stress, and predict the early stage of epilepsy. These pathways were most closely related to neuroinflammation and oxidative stress, and predicted drug-target relationships in the previously studied pathways;molecular docking results showed that the top 5 molecules bound more tightly to the top 6 targets;molecular dynamics simulations showed that ESR1 bound stably and tightly to naringenin, suggesting that regulation of estrogen levels may be one of the potential mechanisms of action of velvet calamus capsules in the treatment of epilepsy. |
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