Network pharmacology-based study on the mechanism of Yiwei Decoction in chronic atrophic gastritis and experimental assessment

Objective: Yiwei Decoction (YWD) is an ancient TCM formula with historical use in treating chronic atrophic gastritis (CAG). However, its pharmacodynamic mechanisms remain poorly understood. This study aims to study the effect of YWD on CAG through network pharmacology and experimental verification....

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Main Authors: Zepeng Zhang, Ju Liu, Yi Wang, Xiwen Li, Manman Guo, Menglei Ding, Tongtong Zhu, Lei Zhang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-12-01
Series:Journal of Holistic Integrative Pharmacy
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Online Access:http://www.sciencedirect.com/science/article/pii/S270736882400061X
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author Zepeng Zhang
Ju Liu
Yi Wang
Xiwen Li
Manman Guo
Menglei Ding
Tongtong Zhu
Lei Zhang
author_facet Zepeng Zhang
Ju Liu
Yi Wang
Xiwen Li
Manman Guo
Menglei Ding
Tongtong Zhu
Lei Zhang
author_sort Zepeng Zhang
collection DOAJ
description Objective: Yiwei Decoction (YWD) is an ancient TCM formula with historical use in treating chronic atrophic gastritis (CAG). However, its pharmacodynamic mechanisms remain poorly understood. This study aims to study the effect of YWD on CAG through network pharmacology and experimental verification. Methods: UPLC/MS and the SwissADME database were employed to identify active compounds in YWD. YWD targets were screened by SwissTargetPrediction databases, CAG targets were screened by databases, and the two were intersected for PPI network analysis. The target prediction was performed by GO and KEGG analysis. H2O2-induced injury models were established in zebrafish and GES-1 ​cells, which were subsequently treated with varying doses of YWD. Oxidative stress indicators and apoptosis and inflammation levels in zebrafish and GES-1 ​cells were assessed using fluorescence microscopy, flow cytometry, and microplate reader assays. The binding capabilities of the core components and core targets were examined using molecular docking. Q-PCR and Western blot were employed to analyze the expression levels of Nrf2, Keap1, and HO-1, respectively. Results: Forty-nine compounds were identified from YWD. Network pharmacological analysis suggested that YWD may treat CAG by modulating redox-related signaling pathways, inhibiting apoptosis, and reducing inflammation. Subsequent in vitro and in vivo experiments validated these predictions. YWD effectively mitigated H2O2-induced oxidative stress in zebrafish and GES-1 ​cells, suppressing ROS and decreasing apoptosis. YWD reduced inflammation in gastric epithelial cells. Molecular docking results suggested that methylophiopogonanone A and imperatorin may play a key role in the treatment of YWD. Mechanistically, YWD activated the Nrf2 signaling pathway, downregulated Keap1 expression, and upregulated HO-1 and Bcl2 expression. Conclusion: YWD could improve oxidative stress indicators, inhibiting cell apoptosis, reducing inflammation, and its molecular mechanism of the CAG treatment may be through the Keap1/Nrf2/HO-1 pathways, and to promote the body's antioxidant system.
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spelling doaj-art-e939acfb8397471eb7aae24251f353ec2024-12-31T04:13:28ZengKeAi Communications Co., Ltd.Journal of Holistic Integrative Pharmacy2707-36882024-12-0154277290Network pharmacology-based study on the mechanism of Yiwei Decoction in chronic atrophic gastritis and experimental assessmentZepeng Zhang0Ju Liu1Yi Wang2Xiwen Li3Manman Guo4Menglei Ding5Tongtong Zhu6Lei Zhang7Department of Pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, 215347, ChinaDepartment of Pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, 215347, ChinaDepartment of Pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, 215347, ChinaDepartment of Pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, 215347, ChinaDepartment of Pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, 215347, ChinaDepartment of Pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, 215347, ChinaDepartment of Pharmacy, Kunshan Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, 215332, ChinaDepartment of Pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, 215347, China; Corresponding author.Objective: Yiwei Decoction (YWD) is an ancient TCM formula with historical use in treating chronic atrophic gastritis (CAG). However, its pharmacodynamic mechanisms remain poorly understood. This study aims to study the effect of YWD on CAG through network pharmacology and experimental verification. Methods: UPLC/MS and the SwissADME database were employed to identify active compounds in YWD. YWD targets were screened by SwissTargetPrediction databases, CAG targets were screened by databases, and the two were intersected for PPI network analysis. The target prediction was performed by GO and KEGG analysis. H2O2-induced injury models were established in zebrafish and GES-1 ​cells, which were subsequently treated with varying doses of YWD. Oxidative stress indicators and apoptosis and inflammation levels in zebrafish and GES-1 ​cells were assessed using fluorescence microscopy, flow cytometry, and microplate reader assays. The binding capabilities of the core components and core targets were examined using molecular docking. Q-PCR and Western blot were employed to analyze the expression levels of Nrf2, Keap1, and HO-1, respectively. Results: Forty-nine compounds were identified from YWD. Network pharmacological analysis suggested that YWD may treat CAG by modulating redox-related signaling pathways, inhibiting apoptosis, and reducing inflammation. Subsequent in vitro and in vivo experiments validated these predictions. YWD effectively mitigated H2O2-induced oxidative stress in zebrafish and GES-1 ​cells, suppressing ROS and decreasing apoptosis. YWD reduced inflammation in gastric epithelial cells. Molecular docking results suggested that methylophiopogonanone A and imperatorin may play a key role in the treatment of YWD. Mechanistically, YWD activated the Nrf2 signaling pathway, downregulated Keap1 expression, and upregulated HO-1 and Bcl2 expression. Conclusion: YWD could improve oxidative stress indicators, inhibiting cell apoptosis, reducing inflammation, and its molecular mechanism of the CAG treatment may be through the Keap1/Nrf2/HO-1 pathways, and to promote the body's antioxidant system.http://www.sciencedirect.com/science/article/pii/S270736882400061XYiwei DecoctionChronic atrophic gastritisNetwork pharmacologyZebrafishGES-1Oxidative stress
spellingShingle Zepeng Zhang
Ju Liu
Yi Wang
Xiwen Li
Manman Guo
Menglei Ding
Tongtong Zhu
Lei Zhang
Network pharmacology-based study on the mechanism of Yiwei Decoction in chronic atrophic gastritis and experimental assessment
Journal of Holistic Integrative Pharmacy
Yiwei Decoction
Chronic atrophic gastritis
Network pharmacology
Zebrafish
GES-1
Oxidative stress
title Network pharmacology-based study on the mechanism of Yiwei Decoction in chronic atrophic gastritis and experimental assessment
title_full Network pharmacology-based study on the mechanism of Yiwei Decoction in chronic atrophic gastritis and experimental assessment
title_fullStr Network pharmacology-based study on the mechanism of Yiwei Decoction in chronic atrophic gastritis and experimental assessment
title_full_unstemmed Network pharmacology-based study on the mechanism of Yiwei Decoction in chronic atrophic gastritis and experimental assessment
title_short Network pharmacology-based study on the mechanism of Yiwei Decoction in chronic atrophic gastritis and experimental assessment
title_sort network pharmacology based study on the mechanism of yiwei decoction in chronic atrophic gastritis and experimental assessment
topic Yiwei Decoction
Chronic atrophic gastritis
Network pharmacology
Zebrafish
GES-1
Oxidative stress
url http://www.sciencedirect.com/science/article/pii/S270736882400061X
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