Abstract | ETHNOPHARMACOLOGICAL RELEVANCE: AIM OF THE STUDY: The aim of this study was to investigate the anti- fibrosis effect of XYS and to explore the molecular mechanisms by combining network pharmacology and transcriptomic technologies. MATERIALS AND METHODS: The carbon tetrachloride (CCl4)-induced liver fibrosis rat were treated with three doses of XYS. The liver fibrosis and function were evaluated by histopathological examination and serum biochemical detection. The fibrosis related protein a-SMA and collagen I were assessed by Western blot. Different expressed genes (DEGs) between XYS-treated group and model group were analyzed. The herb-component-target network was constructed combined the network pharmacology. The predict targets and pathways were validated by in vitro and in vivo experiments. RESULTS: With XYS treatment, the liver function was significantly improved, and fibrotic changes were alleviated. The a-SMA and collagen I expression levels in the liver were also decreased in XYS-treated rats compared with CCl4 model rats. 108 active components and 42 targets from 8 herbs constituted herb-compound-target network by transcriptomics and network pharmacology analysis. The KEGG pathway and GO enrichment analyses showed that the FoxO, TGFβ, AMPK, MAPK, PPAR, and hepatitis B and C pathways were involved in the anti- fibrosis effects of XYS. In the liver tissues, p-FoxO3a and p-Akt expression levels were significantly increased in the CCl4 model group but decreased in the XYS-treated group. The TGFβ1/Smad pathway and Akt/FoxO3 pathway were verified in LX2 cells by inhibiting phosphorylation of Smad3 and Akt activity, respectively. CONCLUSIONS: Our findings suggested that XYS markedly alleviated CCl4-induced liver fibrosis in histopathological and serum liver function analyses, and this effect may occur via the TGFβ1/Smad and Akt/FoxO signaling pathways.
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Authors | Yuan Zhou, Rong Wu, Fei-Fei Cai, Wen-Jun Zhou, Yi-Yu Lu, Hui Zhang, Qi-Long Chen, Shi-Bing Su |
Journal | Journal of ethnopharmacology
(J Ethnopharmacol)
Vol. 264
Pg. 113021
(Jan 10 2021)
ISSN: 1872-7573 [Electronic] Ireland |
PMID | 32479885
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 Elsevier B.V. All rights reserved. |
Chemical References |
- Drugs, Chinese Herbal
- FOXO3 protein, rat
- Forkhead Box Protein O3
- Smad3 Protein
- Smad3 protein, rat
- Transforming Growth Factor beta
- xiaoyaosan
- Proto-Oncogene Proteins c-akt
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Topics |
- Animals
- Drugs, Chinese Herbal
(pharmacology, therapeutic use)
- Forkhead Box Protein O3
(antagonists & inhibitors, metabolism)
- Liver Cirrhosis
(drug therapy, metabolism)
- Male
- Protein Interaction Maps
(drug effects, physiology)
- Proto-Oncogene Proteins c-akt
(antagonists & inhibitors, metabolism)
- Rats
- Rats, Wistar
- Signal Transduction
(drug effects, physiology)
- Smad3 Protein
(antagonists & inhibitors, metabolism)
- Transforming Growth Factor beta
(antagonists & inhibitors, metabolism)
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