{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:12:28Z","timestamp":1790946748508,"version":"4.1.0"},"reference-count":45,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intervirology"],"abstract":"<jats:p>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-\u03b1), phosphorylated-PPAR-\u03b1 (p-PPAR-\u03b1), CYP27, \u03b1-smooth muscle actin (\u03b1-SMA), connective tissue growth factor (CTGF), and Integrin-\u03b21, 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. <\/jats:p>","DOI":"10.1159\/000542355","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T17:00:59Z","timestamp":1733504459000},"page":"119-135","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Biological Mechanisms of Action of Chrysophanol in Hepatic Stellate Cells Activated by Hepatic B Virus X Based on Network 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