Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia–reperfusion induced acute kidney injury based on gut–kidney crosstalk
This study aimed to explore the mechanism of Xiaoyu Xiezhuo decoction (XXD) on ischemia–reperfusion-induced acute kidney injury (IRI-AKI) using network pharmacology methods and gut microbiota analysis. A total of 1778 AKI-related targets were obtained, including 140 targets possibly regulated by AKI...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Renal Failure |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2365982 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849689344948830208 |
|---|---|
| author | Yue Ji Yunming Xiao Shipian Li Yihua Fan Yuzi Cai Bo Yang Hongbo Chen Shouci Hu |
| author_facet | Yue Ji Yunming Xiao Shipian Li Yihua Fan Yuzi Cai Bo Yang Hongbo Chen Shouci Hu |
| author_sort | Yue Ji |
| collection | DOAJ |
| description | This study aimed to explore the mechanism of Xiaoyu Xiezhuo decoction (XXD) on ischemia–reperfusion-induced acute kidney injury (IRI-AKI) using network pharmacology methods and gut microbiota analysis. A total of 1778 AKI-related targets were obtained, including 140 targets possibly regulated by AKI in XXD, indicating that the core targets were mainly enriched in inflammatory-related pathways, such as the IL-17 signaling pathway and TNF signaling pathway. The unilateral IRI-AKI animal model was established and randomly divided into four groups: the sham group, the AKI group, the sham + XXD group, and the AKI + XXD group. Compared with the rats in the AKI group, XXD improved not only renal function, urinary enzymes, and biomarkers of renal damage such as Kim-1, cystatin C, and serum inflammatory factors such as IL-17, TNF-α, IL-6, and IL 1-β, but also intestinal metabolites including lipopolysaccharides, d-lactic acid, indoxyl sulfate, p-cresyl sulfate, and short-chain fatty acids. XXD ameliorated renal and colonic pathological injury as well as inflammation and chemokine gene abundance, such as IL-17, TNF-α, IL-6, IL-1β, ICAM-1, and MCP-1, in AKI rats via the TLR4/NF-κB/NLRP3 pathway, reducing the AKI score, renal pathological damage, and improving the intestinal mucosa’s inflammatory infiltration. It also repaired markers of the mucosal barrier, including claudin-1, occludin, and ZO-1. Compared with the rats in the AKI group, the α diversity was significantly increased, and the Chao1 index was significantly enhanced after XXD treatment in both the sham group and the AKI group. The treatment group significantly reversed this change in microbiota. |
| format | Article |
| id | doaj-art-ff930c83ef4241fb8bac31e05b13d2c1 |
| institution | DOAJ |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-ff930c83ef4241fb8bac31e05b13d2c12025-08-20T03:21:40ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2365982Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia–reperfusion induced acute kidney injury based on gut–kidney crosstalkYue Ji0Yunming Xiao1Shipian Li2Yihua Fan3Yuzi Cai4Bo Yang5Hongbo Chen6Shouci Hu7Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, PR ChinaDepartment of Nephrology, Medical School of Chinese PLA, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, PR ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, PR ChinaDepartment of Rheumatism and Immunity, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, PR ChinaInstitute of Nephrology & Beijing Key Laboratory, Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Beijing, PR ChinaDepartment of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, PR ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, PR ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, PR ChinaThis study aimed to explore the mechanism of Xiaoyu Xiezhuo decoction (XXD) on ischemia–reperfusion-induced acute kidney injury (IRI-AKI) using network pharmacology methods and gut microbiota analysis. A total of 1778 AKI-related targets were obtained, including 140 targets possibly regulated by AKI in XXD, indicating that the core targets were mainly enriched in inflammatory-related pathways, such as the IL-17 signaling pathway and TNF signaling pathway. The unilateral IRI-AKI animal model was established and randomly divided into four groups: the sham group, the AKI group, the sham + XXD group, and the AKI + XXD group. Compared with the rats in the AKI group, XXD improved not only renal function, urinary enzymes, and biomarkers of renal damage such as Kim-1, cystatin C, and serum inflammatory factors such as IL-17, TNF-α, IL-6, and IL 1-β, but also intestinal metabolites including lipopolysaccharides, d-lactic acid, indoxyl sulfate, p-cresyl sulfate, and short-chain fatty acids. XXD ameliorated renal and colonic pathological injury as well as inflammation and chemokine gene abundance, such as IL-17, TNF-α, IL-6, IL-1β, ICAM-1, and MCP-1, in AKI rats via the TLR4/NF-κB/NLRP3 pathway, reducing the AKI score, renal pathological damage, and improving the intestinal mucosa’s inflammatory infiltration. It also repaired markers of the mucosal barrier, including claudin-1, occludin, and ZO-1. Compared with the rats in the AKI group, the α diversity was significantly increased, and the Chao1 index was significantly enhanced after XXD treatment in both the sham group and the AKI group. The treatment group significantly reversed this change in microbiota.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2365982Xiaoyu Xiezhuo decoctionnetwork pharmacologyacute kidney injurygut flora |
| spellingShingle | Yue Ji Yunming Xiao Shipian Li Yihua Fan Yuzi Cai Bo Yang Hongbo Chen Shouci Hu Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia–reperfusion induced acute kidney injury based on gut–kidney crosstalk Renal Failure Xiaoyu Xiezhuo decoction network pharmacology acute kidney injury gut flora |
| title | Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia–reperfusion induced acute kidney injury based on gut–kidney crosstalk |
| title_full | Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia–reperfusion induced acute kidney injury based on gut–kidney crosstalk |
| title_fullStr | Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia–reperfusion induced acute kidney injury based on gut–kidney crosstalk |
| title_full_unstemmed | Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia–reperfusion induced acute kidney injury based on gut–kidney crosstalk |
| title_short | Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia–reperfusion induced acute kidney injury based on gut–kidney crosstalk |
| title_sort | protective effect and mechanism of xiaoyu xiezhuo decoction on ischemia reperfusion induced acute kidney injury based on gut kidney crosstalk |
| topic | Xiaoyu Xiezhuo decoction network pharmacology acute kidney injury gut flora |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2365982 |
| work_keys_str_mv | AT yueji protectiveeffectandmechanismofxiaoyuxiezhuodecoctiononischemiareperfusioninducedacutekidneyinjurybasedongutkidneycrosstalk AT yunmingxiao protectiveeffectandmechanismofxiaoyuxiezhuodecoctiononischemiareperfusioninducedacutekidneyinjurybasedongutkidneycrosstalk AT shipianli protectiveeffectandmechanismofxiaoyuxiezhuodecoctiononischemiareperfusioninducedacutekidneyinjurybasedongutkidneycrosstalk AT yihuafan protectiveeffectandmechanismofxiaoyuxiezhuodecoctiononischemiareperfusioninducedacutekidneyinjurybasedongutkidneycrosstalk AT yuzicai protectiveeffectandmechanismofxiaoyuxiezhuodecoctiononischemiareperfusioninducedacutekidneyinjurybasedongutkidneycrosstalk AT boyang protectiveeffectandmechanismofxiaoyuxiezhuodecoctiononischemiareperfusioninducedacutekidneyinjurybasedongutkidneycrosstalk AT hongbochen protectiveeffectandmechanismofxiaoyuxiezhuodecoctiononischemiareperfusioninducedacutekidneyinjurybasedongutkidneycrosstalk AT shoucihu protectiveeffectandmechanismofxiaoyuxiezhuodecoctiononischemiareperfusioninducedacutekidneyinjurybasedongutkidneycrosstalk |