Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammation
Abstract Chronic kidney disease (CKD) is a major health concern, with renal interstitial fibrosis (RIF) as a key feature. Effective management of RIF is crucial for treating CKD. Yiqi Juanshen decoction (YQJSD), as traditional Chinese medicine, has shown promising results in CKD treatment. This stud...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-86622-7 |
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| author | Kaiyue Tan Jingwei Deng Yi Liu Yudi Zhang Yu Xiong Su Yuan Jun Liu Zhiwei Chen Yuanyuan Liu Wenfu Cao |
| author_facet | Kaiyue Tan Jingwei Deng Yi Liu Yudi Zhang Yu Xiong Su Yuan Jun Liu Zhiwei Chen Yuanyuan Liu Wenfu Cao |
| author_sort | Kaiyue Tan |
| collection | DOAJ |
| description | Abstract Chronic kidney disease (CKD) is a major health concern, with renal interstitial fibrosis (RIF) as a key feature. Effective management of RIF is crucial for treating CKD. Yiqi Juanshen decoction (YQJSD), as traditional Chinese medicine, has shown promising results in CKD treatment. This study evaluates YQJSD’s effectiveness in ameliorating RIF and explores the underlying molecular mechanisms using the unilateral ureteral obstruction (UUO) model. YQJSD has been shown to effectively reduce serum creatinine and blood urea nitrogen levels, decrease extracellular matrix deposition, and down-regulate the expression of α-SMA, COL4α1, Fibronectin (FN). Mechanistically, YQJSD exerts its effects by modulating multiple pathways: it inhibits the NF-κB signaling pathway, inhibiting the expression of pro-inflammatory cytokines like NF-κB1, IL-1β, TNF-α, and CCR1. Simultaneously, YQJSD suppresses the epithelial-mesenchymal transition (EMT) by downregulating the expression of Snail1, Vimentin, Twist1, and FSP1, while increasing E-cadherin expression. Moreover, YQJSD can regulate the PI3K/AKT signaling pathway by decreasing the expression of LOXL2 and PIK3R1, along with p-AKT1/2/3. This modulation of the LOXL2/PI3K/AKT pathway contributes to the inhibition of both EMT and inflammation, highlighting a critical role in the therapeutic intervention against RIF. These findings suggest that YQJSD may serve as a promising therapeutic management of RIF in CKD patients. |
| format | Article |
| id | doaj-art-5f9e496032cf4227a42146ead914be5d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-5f9e496032cf4227a42146ead914be5d2025-02-09T12:29:59ZengNature PortfolioScientific Reports2045-23222025-02-0115111510.1038/s41598-025-86622-7Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammationKaiyue Tan0Jingwei Deng1Yi Liu2Yudi Zhang3Yu Xiong4Su Yuan5Jun Liu6Zhiwei Chen7Yuanyuan Liu8Wenfu Cao9Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical UniversityChongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical UniversityChongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical UniversityCollege of Combination of Chinese and Western Medicine, Chongqing College of Traditional Chinese MedicineChongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical UniversityChongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical UniversityChongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical UniversityChongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical UniversityDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical UniversityChongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical UniversityAbstract Chronic kidney disease (CKD) is a major health concern, with renal interstitial fibrosis (RIF) as a key feature. Effective management of RIF is crucial for treating CKD. Yiqi Juanshen decoction (YQJSD), as traditional Chinese medicine, has shown promising results in CKD treatment. This study evaluates YQJSD’s effectiveness in ameliorating RIF and explores the underlying molecular mechanisms using the unilateral ureteral obstruction (UUO) model. YQJSD has been shown to effectively reduce serum creatinine and blood urea nitrogen levels, decrease extracellular matrix deposition, and down-regulate the expression of α-SMA, COL4α1, Fibronectin (FN). Mechanistically, YQJSD exerts its effects by modulating multiple pathways: it inhibits the NF-κB signaling pathway, inhibiting the expression of pro-inflammatory cytokines like NF-κB1, IL-1β, TNF-α, and CCR1. Simultaneously, YQJSD suppresses the epithelial-mesenchymal transition (EMT) by downregulating the expression of Snail1, Vimentin, Twist1, and FSP1, while increasing E-cadherin expression. Moreover, YQJSD can regulate the PI3K/AKT signaling pathway by decreasing the expression of LOXL2 and PIK3R1, along with p-AKT1/2/3. This modulation of the LOXL2/PI3K/AKT pathway contributes to the inhibition of both EMT and inflammation, highlighting a critical role in the therapeutic intervention against RIF. These findings suggest that YQJSD may serve as a promising therapeutic management of RIF in CKD patients.https://doi.org/10.1038/s41598-025-86622-7Traditional Chinese medicineRenal interstitial fibrosisEMTInflammationLOXL2/PI3K/AKT pathway |
| spellingShingle | Kaiyue Tan Jingwei Deng Yi Liu Yudi Zhang Yu Xiong Su Yuan Jun Liu Zhiwei Chen Yuanyuan Liu Wenfu Cao Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammation Scientific Reports Traditional Chinese medicine Renal interstitial fibrosis EMT Inflammation LOXL2/PI3K/AKT pathway |
| title | Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammation |
| title_full | Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammation |
| title_fullStr | Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammation |
| title_full_unstemmed | Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammation |
| title_short | Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammation |
| title_sort | yiqi juanshen decoction alleviates renal interstitial fibrosis by targeting the loxl2 pi3k akt pathway to suppress emt and inflammation |
| topic | Traditional Chinese medicine Renal interstitial fibrosis EMT Inflammation LOXL2/PI3K/AKT pathway |
| url | https://doi.org/10.1038/s41598-025-86622-7 |
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