Pharmacological Mechanism of Zuojin Pill for Gastroesophageal Reflux Disease: A Network Pharmacology Study.
Saved in:
| Title: | Pharmacological Mechanism of Zuojin Pill for Gastroesophageal Reflux Disease: A Network Pharmacology Study. |
|---|---|
| Authors: | Lv, Mi1,2 (AUTHOR), Huang, Jinke1,2 (AUTHOR), Hu, Jiayan1,2 (AUTHOR), Yu, Wenxi2,3 (AUTHOR), Liu, Ping1,2 (AUTHOR), Zhang, Kunli1,2 (AUTHOR), Wang, Fengyun1,2 (AUTHOR) |
| Source: | Journal of Food Quality. 8/27/2022, p1-13. 13p. |
| Subjects: | Gastroesophageal reflux, Tumor suppressor genes, Molecular dynamics, Fos oncogenes, Pharmacology, Oncogenes, Gene regulatory networks |
| Geographic Terms: | China |
| Abstract: | Background. Although Zuojin Pill (ZJP) is widely used in China as a traditional prescription to treat gastroesophageal reflux disease (GERD), its exact mechanism of action is still unknown. Therefore, we employed network pharmacology (NP), molecular docking (MD), and molecular dynamics simulation (MDS) to investigate the pharmacological mechanisms of ZJP against GERD. Methods. Active compounds and target genes corresponding to ZJP and target genes related to GERD were identified through analysis of publicly available datasets. Subsequently, the obtained data were subjected to further network pharmacological analysis to explore the potential key active compounds, core target genes, and biological processes (BPs) associated with the effect of ZJP against GERD. Finally, the prediction results of NP were validated by MD, and MDS of the optimal core protein-ligand for each component obtained by MD were performed using Gromacs 2020 software. Results. Twelve active components of ZJP were identified to act on 82 target genes associated with GERD, and ZJP might exert an anti-GERD effect through the regulation of BPs such as reactive oxygen species (ROS) metabolism, response to oxidative stress (OS), and ROS, as well as the activation of signaling pathways such as apoptosis, p53 signaling, chemical carcinogenesis-ROS, and HIF-1 signaling pathways. Furthermore, quercetin, kaempferol, and coptisine, the three key components of ZJP were shown to stably bond with the 14 core target genes, including AKT1, MMP2, TP53, EGFR, JUN, CASP3, CXCL8, HIF1α, IL-1β, MYC, PPARG, MMP9, PTGS2, and FOS. Results from MDS showed that PPARG-quercetin and MMP2-quercetin bound more stably. Conclusions. The findings suggest that ZJP alleviates the symptoms of GERD and improves the prognosis by regulating ROS metabolism, thereby reducing the secretion of proinflammatory cytokines like IL-1β, COX-2, CXCL8, and MMPs, regulating the expression of oncogenes such as JUN and FOS, and maintaining the normal expression of tumor suppressor genes such as TP53 and MYC. However, whether the effect of this modulation of ROS metabolism is positive or negative needs to be further verified by pharmacological experiments. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Food Quality is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
|
Full text is not displayed to guests.
Login for full access.
|
|
| Abstract: | Background. Although Zuojin Pill (ZJP) is widely used in China as a traditional prescription to treat gastroesophageal reflux disease (GERD), its exact mechanism of action is still unknown. Therefore, we employed network pharmacology (NP), molecular docking (MD), and molecular dynamics simulation (MDS) to investigate the pharmacological mechanisms of ZJP against GERD. Methods. Active compounds and target genes corresponding to ZJP and target genes related to GERD were identified through analysis of publicly available datasets. Subsequently, the obtained data were subjected to further network pharmacological analysis to explore the potential key active compounds, core target genes, and biological processes (BPs) associated with the effect of ZJP against GERD. Finally, the prediction results of NP were validated by MD, and MDS of the optimal core protein-ligand for each component obtained by MD were performed using Gromacs 2020 software. Results. Twelve active components of ZJP were identified to act on 82 target genes associated with GERD, and ZJP might exert an anti-GERD effect through the regulation of BPs such as reactive oxygen species (ROS) metabolism, response to oxidative stress (OS), and ROS, as well as the activation of signaling pathways such as apoptosis, p53 signaling, chemical carcinogenesis-ROS, and HIF-1 signaling pathways. Furthermore, quercetin, kaempferol, and coptisine, the three key components of ZJP were shown to stably bond with the 14 core target genes, including AKT1, MMP2, TP53, EGFR, JUN, CASP3, CXCL8, HIF1α, IL-1β, MYC, PPARG, MMP9, PTGS2, and FOS. Results from MDS showed that PPARG-quercetin and MMP2-quercetin bound more stably. Conclusions. The findings suggest that ZJP alleviates the symptoms of GERD and improves the prognosis by regulating ROS metabolism, thereby reducing the secretion of proinflammatory cytokines like IL-1β, COX-2, CXCL8, and MMPs, regulating the expression of oncogenes such as JUN and FOS, and maintaining the normal expression of tumor suppressor genes such as TP53 and MYC. However, whether the effect of this modulation of ROS metabolism is positive or negative needs to be further verified by pharmacological experiments. [ABSTRACT FROM AUTHOR] |
|---|---|
| ISSN: | 01469428 |
| DOI: | 10.1155/2022/5933348 |
