Molecular Biological Mechanisms of Action of Chrysophanol in Hepatic Stellate Cells Activated by Hepatic B Virus X Based on Network Pharmacology
Introduction: Chrysophanol (Cho) is a natural anthraquinone with biological effects such as inducing ferroptosis and anticancer activity. The hepatitis B virus X protein (HBx) is essential for HBV replication. We aimed to identify the key pathways in HBx-induced hepatic stellate cell (HSC...
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| Format: | Article |
| Language: | English |
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Karger Publishers
2024-01-01
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| Series: | Intervirology |
| Online Access: | https://karger.com/article/doi/10.1159/000542355 |
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| author | Chih-Hung Lin Ching-Feng Cheng Yi-Shiou Chiou Inga Wang Chan-Yen Kuo |
| author_facet | Chih-Hung Lin Ching-Feng Cheng Yi-Shiou Chiou Inga Wang Chan-Yen Kuo |
| author_sort | Chih-Hung Lin |
| collection | DOAJ |
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Introduction: Chrysophanol (Cho) is a natural anthraquinone with biological effects such as inducing ferroptosis and anticancer activity. The hepatitis B virus X protein (HBx) is essential for HBV replication. We aimed to identify the key pathways in HBx-induced hepatic stellate cell (HSC) activation and to characterize the potential mechanisms of action of Cho against liver fibrosis. Methods: HSC-T6 cells were transfected with FLAG (control group) or FLAG-HBx (HBx group), and RNA sequencing and Western blotting analysis were conducted to assess the effects of HBx and Cho on specific molecular targets and signaling pathways. Results: Gene ontology and pathway analyses indicated that the genes targeted by HBx participate in immunological responses, chemokine and cytokine activity, cell-substrate adhesion, extracellular matrix organization, growth factor binding, defense responses, and antigen processing and presentation. RNA-seq and Western blotting data revealed that HBx-activated HSC-T6 cells exhibited upregulated expression of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), S6, phosphorylated S6 (p-S6), peroxisome proliferator-activated receptor (PPAR-α), phosphorylated-PPAR-α (p-PPAR-α), CYP27, α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and Integrin-β1, which was reversed after treatment with Cho. These results were also verified in a HBx-activated HSC-T6 and LX-2 cell model and thioacetamide-induced liver fibrosis mouse model. Conclusions: Thus, our findings indicate that Cho ameliorates HBx-induced HSC activation and liver fibrosis via inhibition of the mTOR and PPARs signaling pathways, suggesting that Cho is a potential therapeutic for chronic liver inflammation-mediated diseases. |
| format | Article |
| id | doaj-art-5f6999fb158146f4a1c2c2bb3d76751f |
| institution | OA Journals |
| issn | 1423-0100 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Karger Publishers |
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| series | Intervirology |
| spelling | doaj-art-5f6999fb158146f4a1c2c2bb3d76751f2025-08-20T02:31:55ZengKarger PublishersIntervirology1423-01002024-01-0167111913510.1159/000542355Molecular Biological Mechanisms of Action of Chrysophanol in Hepatic Stellate Cells Activated by Hepatic B Virus X Based on Network PharmacologyChih-Hung LinChing-Feng ChengYi-Shiou ChiouInga WangChan-Yen Kuohttps://orcid.org/0000-0002-5702-5730 Introduction: Chrysophanol (Cho) is a natural anthraquinone with biological effects such as inducing ferroptosis and anticancer activity. The hepatitis B virus X protein (HBx) is essential for HBV replication. We aimed to identify the key pathways in HBx-induced hepatic stellate cell (HSC) activation and to characterize the potential mechanisms of action of Cho against liver fibrosis. Methods: HSC-T6 cells were transfected with FLAG (control group) or FLAG-HBx (HBx group), and RNA sequencing and Western blotting analysis were conducted to assess the effects of HBx and Cho on specific molecular targets and signaling pathways. Results: Gene ontology and pathway analyses indicated that the genes targeted by HBx participate in immunological responses, chemokine and cytokine activity, cell-substrate adhesion, extracellular matrix organization, growth factor binding, defense responses, and antigen processing and presentation. RNA-seq and Western blotting data revealed that HBx-activated HSC-T6 cells exhibited upregulated expression of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), S6, phosphorylated S6 (p-S6), peroxisome proliferator-activated receptor (PPAR-α), phosphorylated-PPAR-α (p-PPAR-α), CYP27, α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and Integrin-β1, which was reversed after treatment with Cho. These results were also verified in a HBx-activated HSC-T6 and LX-2 cell model and thioacetamide-induced liver fibrosis mouse model. Conclusions: Thus, our findings indicate that Cho ameliorates HBx-induced HSC activation and liver fibrosis via inhibition of the mTOR and PPARs signaling pathways, suggesting that Cho is a potential therapeutic for chronic liver inflammation-mediated diseases. https://karger.com/article/doi/10.1159/000542355 |
| spellingShingle | Chih-Hung Lin Ching-Feng Cheng Yi-Shiou Chiou Inga Wang Chan-Yen Kuo Molecular Biological Mechanisms of Action of Chrysophanol in Hepatic Stellate Cells Activated by Hepatic B Virus X Based on Network Pharmacology Intervirology |
| title | Molecular Biological Mechanisms of Action of Chrysophanol in Hepatic Stellate Cells Activated by Hepatic B Virus X Based on Network Pharmacology |
| title_full | Molecular Biological Mechanisms of Action of Chrysophanol in Hepatic Stellate Cells Activated by Hepatic B Virus X Based on Network Pharmacology |
| title_fullStr | Molecular Biological Mechanisms of Action of Chrysophanol in Hepatic Stellate Cells Activated by Hepatic B Virus X Based on Network Pharmacology |
| title_full_unstemmed | Molecular Biological Mechanisms of Action of Chrysophanol in Hepatic Stellate Cells Activated by Hepatic B Virus X Based on Network Pharmacology |
| title_short | Molecular Biological Mechanisms of Action of Chrysophanol in Hepatic Stellate Cells Activated by Hepatic B Virus X Based on Network Pharmacology |
| title_sort | molecular biological mechanisms of action of chrysophanol in hepatic stellate cells activated by hepatic b virus x based on network pharmacology |
| url | https://karger.com/article/doi/10.1159/000542355 |
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