Academic Journal
Aloe-emodin ameliorates non-alcoholic fatty liver disease by regulating the ZNRF3/Wnt/β-catenin axis and suppressing hepatic lipogenesis.
| Τίτλος: | Aloe-emodin ameliorates non-alcoholic fatty liver disease by regulating the ZNRF3/Wnt/β-catenin axis and suppressing hepatic lipogenesis. |
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| Συγγραφείς: | Li W; Department of Infection, The First Hospital of Changsha, Changsha, Hunan, 410011, China., Pan M; Department of Infection, The First Hospital of Changsha, Changsha, Hunan, 410011, China. Electronic address: iris18711055073@163.com., Tang J; Department of Infection, The First Hospital of Changsha, Changsha, Hunan, 410011, China. |
| Πηγή: | Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2026 Aug 20; Vol. 827, pp. 153979. Date of Electronic Publication: 2026 May 19. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2002- >: San Diego, CA : Elsevier Original Publication: New York, Academic Press. |
| Ιατρικοί όροι (MeSH): | Non-alcoholic Fatty Liver Disease*/drug therapy , Non-alcoholic Fatty Liver Disease*/metabolism , Non-alcoholic Fatty Liver Disease*/pathology , Lipogenesis*/drug effects , Anthraquinones*/pharmacology , Anthraquinones*/therapeutic use , Wnt Signaling Pathway*/drug effects , Liver*/drug effects , Liver*/metabolism , Liver*/pathology , Ubiquitin-Protein Ligases*/metabolism, Diet, High-Fat/adverse effects ; beta Catenin/metabolism ; Hepatocytes/drug effects ; Hepatocytes/metabolism ; Animals ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation |
| Περίληψη: | Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with limited approved pharmacological treatment options, creating an urgent need for novel therapeutic agents. This study investigated the efficacy and underlying molecular mechanism of aloe-emodin, a natural anthraquinone from Rhei Radix et Rhizoma, in treating NAFLD. In a high-fat diet (HFD)-induced mouse model, aloe-emodin administration significantly reduced body and liver weight, ameliorated hepatic steatosis, lowered serum ALT and hepatic lipid levels, and suppressed the expression of key lipogenic genes. These protective effects were recapitulated in an in vitro model using free fatty acid (FFA)-treated hepatocytes, where aloe-emodin reduced intracellular lipid accumulation without affecting cell viability. Mechanistic investigation revealed that aloe-emodin restored AMPK activation, increased PPARα-associated fatty acid oxidation markers, and suppressed Wnt/β-catenin signaling. Functional rescue experiments further supported the involvement of the ZNRF3-Wnt/β-catenin axis in the anti-lipogenic effects of aloe-emodin. Molecular docking identified ZNRF3, a critical negative regulator of the Wnt pathway, as the top potential binding target for aloe-emodin. We confirmed that ZNRF3 expression, which was downregulated in NAFLD models, was significantly restored by aloe-emodin treatment. Crucially, rescue experiments demonstrated that the therapeutic and anti-lipogenic effects of aloe-emodin were abolished both in vivo and in vitro when ZNRF3 was genetically knocked down or when the Wnt pathway was pharmacologically activated. These findings suggest that aloe-emodin ameliorates NAFLD, at least in part, by restoring ZNRF3 expression and suppressing Wnt/β-catenin pathway-associated lipogenic activation. (Copyright © 2026. Published by Elsevier Inc.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Aloe-emodin; Hepatic steatosis; Lipogenesis; Non-alcoholic fatty liver disease (NAFLD); Wnt/β-catenin signaling; ZNRF3 |
| Substance Nomenclature: | 0 (Anthraquinones) C8IYT9CR7C (aloe emodin) 0 (beta Catenin) EC 2.3.2.27 (Ubiquitin-Protein Ligases) |
| Entry Date(s): | Date Created: 20260529 Date Completed: 20260613 Latest Revision: 20260613 |
| Update Code: | 20260615 |
| DOI: | 10.1016/j.bbrc.2026.153979 |
| PMID: | 42214922 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1090-2104 |
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| DOI: | 10.1016/j.bbrc.2026.153979 |