Qinggan Yipi capsule ameliorates hepatic fibrosis in rats by down-regulating the TGF-β1/Smad2/3 signaling pathway and improving gut microbiota imbalance
Background and objectiveQinggan Yipi Capsule (QgYp) is a hospital preparation that has been used for many years in the treatment of chronic liver diseases. However, the mechanism of QgYp in ameliorating hepatic fibrosis (HF) remains unclear. This study aims to clarify the anti-liver fibrosis effect...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1525914/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832589813625126912 |
|---|---|
| author | Wenjing Xue Haiqing Liu Ziheng Su Siqi Wang Junping Cheng Yunzhi Pan Lurong Zhang |
| author_facet | Wenjing Xue Haiqing Liu Ziheng Su Siqi Wang Junping Cheng Yunzhi Pan Lurong Zhang |
| author_sort | Wenjing Xue |
| collection | DOAJ |
| description | Background and objectiveQinggan Yipi Capsule (QgYp) is a hospital preparation that has been used for many years in the treatment of chronic liver diseases. However, the mechanism of QgYp in ameliorating hepatic fibrosis (HF) remains unclear. This study aims to clarify the anti-liver fibrosis effect of QgYp and its mechanism of action.MethodsThis study uses a carbon tetrachloride (CCl4) induced HF rat model and TGF-β1 stimulated HSC-T6 cell line (rat HSCs) as experimental models. The therapeutic effects were evaluated through pathology, biochemical tests, and ELISA. The therapeutic mechanism of QgYp for HF was predicted through network pharmacology. The expression of TGF-β1/Smad2/3 related proteins was detected by qPCR analysis and Western blot analysis. The composition of the gut microbiota was analyzed using 16S rRNA gene sequencing.ResultsHistopathological analysis, serum biochemical tests, and ELISA measurements showed that QgYp effectively decreased the levels of ALT, AST, HA, LN, PCIII, and IV-C while improving collagen deposition and hepatocyte necrosis. Protein-protein interaction (PPI) network analysis screened HF-related genes, including peroxisome proliferator-activated receptor gamma (PPARG), tumor necrosis factor (TNF), and TGF-β1. GO and KEGG analyses indicated that QgYp significantly affects TGF-β signaling pathway. In addition, the results of qPCR and Western blot analysis from both in vitro and in vivo experiments indicated that QgYp significantly downregulated the expression of proteins and mRNA associated with the TGF-β1/Smad2/3 pathway. The 16S rDNA gene sequencing results showed that QgYp can increase the diversity and richness of the gut microbiota in HF rats and alter the composition of the gut microbiota.ConclusionQgYp could effectively ameliorate HF, and this effect might be connected to the downregulation of the TGF-β1/Smad2/3 pathway, the suppression of HSCs activation, and regulation of gut microbiota dysbiosis. |
| format | Article |
| id | doaj-art-02343bc8f079472b80b8ba8b75c8b11d |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-02343bc8f079472b80b8ba8b75c8b11d2025-01-24T07:13:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011610.3389/fphar.2025.15259141525914Qinggan Yipi capsule ameliorates hepatic fibrosis in rats by down-regulating the TGF-β1/Smad2/3 signaling pathway and improving gut microbiota imbalanceWenjing Xue0Haiqing Liu1Ziheng Su2Siqi Wang3Junping Cheng4Yunzhi Pan5Lurong Zhang6Key Laboratory for Evaluation and Transformation of Wu Men Medical School’s Empirical Prescriptions, Suzhou Traditional Chinese Medicine Hospital, Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaKey Laboratory for Evaluation and Transformation of Wu Men Medical School’s Empirical Prescriptions, Suzhou Traditional Chinese Medicine Hospital, Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Pharmacy, Affiliated Hospital of Hebei University, Baoding, ChinaDepartment of Pharmacy, Suzhou Fifth People’s Hospital, Suzhou, ChinaKey Laboratory for Evaluation and Transformation of Wu Men Medical School’s Empirical Prescriptions, Suzhou Traditional Chinese Medicine Hospital, Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Pharmacy, Suzhou Fifth People’s Hospital, Suzhou, ChinaKey Laboratory for Evaluation and Transformation of Wu Men Medical School’s Empirical Prescriptions, Suzhou Traditional Chinese Medicine Hospital, Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaBackground and objectiveQinggan Yipi Capsule (QgYp) is a hospital preparation that has been used for many years in the treatment of chronic liver diseases. However, the mechanism of QgYp in ameliorating hepatic fibrosis (HF) remains unclear. This study aims to clarify the anti-liver fibrosis effect of QgYp and its mechanism of action.MethodsThis study uses a carbon tetrachloride (CCl4) induced HF rat model and TGF-β1 stimulated HSC-T6 cell line (rat HSCs) as experimental models. The therapeutic effects were evaluated through pathology, biochemical tests, and ELISA. The therapeutic mechanism of QgYp for HF was predicted through network pharmacology. The expression of TGF-β1/Smad2/3 related proteins was detected by qPCR analysis and Western blot analysis. The composition of the gut microbiota was analyzed using 16S rRNA gene sequencing.ResultsHistopathological analysis, serum biochemical tests, and ELISA measurements showed that QgYp effectively decreased the levels of ALT, AST, HA, LN, PCIII, and IV-C while improving collagen deposition and hepatocyte necrosis. Protein-protein interaction (PPI) network analysis screened HF-related genes, including peroxisome proliferator-activated receptor gamma (PPARG), tumor necrosis factor (TNF), and TGF-β1. GO and KEGG analyses indicated that QgYp significantly affects TGF-β signaling pathway. In addition, the results of qPCR and Western blot analysis from both in vitro and in vivo experiments indicated that QgYp significantly downregulated the expression of proteins and mRNA associated with the TGF-β1/Smad2/3 pathway. The 16S rDNA gene sequencing results showed that QgYp can increase the diversity and richness of the gut microbiota in HF rats and alter the composition of the gut microbiota.ConclusionQgYp could effectively ameliorate HF, and this effect might be connected to the downregulation of the TGF-β1/Smad2/3 pathway, the suppression of HSCs activation, and regulation of gut microbiota dysbiosis.https://www.frontiersin.org/articles/10.3389/fphar.2025.1525914/fullQinggan Yipi capsulehepatic fibrosisTGF-β1/Smad2/3 signaling pathwaygut microbiotanetwork pharmacologyHSC-T6 |
| spellingShingle | Wenjing Xue Haiqing Liu Ziheng Su Siqi Wang Junping Cheng Yunzhi Pan Lurong Zhang Qinggan Yipi capsule ameliorates hepatic fibrosis in rats by down-regulating the TGF-β1/Smad2/3 signaling pathway and improving gut microbiota imbalance Frontiers in Pharmacology Qinggan Yipi capsule hepatic fibrosis TGF-β1/Smad2/3 signaling pathway gut microbiota network pharmacology HSC-T6 |
| title | Qinggan Yipi capsule ameliorates hepatic fibrosis in rats by down-regulating the TGF-β1/Smad2/3 signaling pathway and improving gut microbiota imbalance |
| title_full | Qinggan Yipi capsule ameliorates hepatic fibrosis in rats by down-regulating the TGF-β1/Smad2/3 signaling pathway and improving gut microbiota imbalance |
| title_fullStr | Qinggan Yipi capsule ameliorates hepatic fibrosis in rats by down-regulating the TGF-β1/Smad2/3 signaling pathway and improving gut microbiota imbalance |
| title_full_unstemmed | Qinggan Yipi capsule ameliorates hepatic fibrosis in rats by down-regulating the TGF-β1/Smad2/3 signaling pathway and improving gut microbiota imbalance |
| title_short | Qinggan Yipi capsule ameliorates hepatic fibrosis in rats by down-regulating the TGF-β1/Smad2/3 signaling pathway and improving gut microbiota imbalance |
| title_sort | qinggan yipi capsule ameliorates hepatic fibrosis in rats by down regulating the tgf β1 smad2 3 signaling pathway and improving gut microbiota imbalance |
| topic | Qinggan Yipi capsule hepatic fibrosis TGF-β1/Smad2/3 signaling pathway gut microbiota network pharmacology HSC-T6 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1525914/full |
| work_keys_str_mv | AT wenjingxue qingganyipicapsuleameliorateshepaticfibrosisinratsbydownregulatingthetgfb1smad23signalingpathwayandimprovinggutmicrobiotaimbalance AT haiqingliu qingganyipicapsuleameliorateshepaticfibrosisinratsbydownregulatingthetgfb1smad23signalingpathwayandimprovinggutmicrobiotaimbalance AT zihengsu qingganyipicapsuleameliorateshepaticfibrosisinratsbydownregulatingthetgfb1smad23signalingpathwayandimprovinggutmicrobiotaimbalance AT siqiwang qingganyipicapsuleameliorateshepaticfibrosisinratsbydownregulatingthetgfb1smad23signalingpathwayandimprovinggutmicrobiotaimbalance AT junpingcheng qingganyipicapsuleameliorateshepaticfibrosisinratsbydownregulatingthetgfb1smad23signalingpathwayandimprovinggutmicrobiotaimbalance AT yunzhipan qingganyipicapsuleameliorateshepaticfibrosisinratsbydownregulatingthetgfb1smad23signalingpathwayandimprovinggutmicrobiotaimbalance AT lurongzhang qingganyipicapsuleameliorateshepaticfibrosisinratsbydownregulatingthetgfb1smad23signalingpathwayandimprovinggutmicrobiotaimbalance |