Academic Journal
Euphorbia factor L3 ameliorates hepatic steatosis by activating LKB1-AMPK signaling pathway-regulated lipid metabolism.
| Τίτλος: | Euphorbia factor L3 ameliorates hepatic steatosis by activating LKB1-AMPK signaling pathway-regulated lipid metabolism. |
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| Συγγραφείς: | Fang Y; Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education; Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming 650091, PR China., Liu H; Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education; Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming 650091, PR China., Jiang F; Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education; Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming 650091, PR China., Lu Q; Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education; Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming 650091, PR China., Huang B; Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education; Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming 650091, PR China., Mao C; Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education; Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming 650091, PR China., Long Q; Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education; Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming 650091, PR China., Zhou Q; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences (CAS), Kunming 650223, PR China., Yang X; Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education; Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming 650091, PR China. Electronic address: xdyang@ynu.edu.cn., Cao J; State Key Laboratory of Vegetation Structure, Functions and Construction (Veglab), Ministry of Education; Key Laboratory for Transboundary Ecosecurity of Southwest China, Yunnan Key Laboratory of Plant Reproductive Adaptation and Evolutionary Ecology, Institute of Biodiversity, School of Ecology and Environmental Science, Yunnan University, 650500 Kunming, PR China. Electronic address: juncao@vip.163.com., Xiong W; Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education; Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming 650091, PR China. Electronic address: xwy@ynu.edu.cn. |
| Πηγή: | Bioorganic chemistry [Bioorg Chem] 2026 Sep 05; Vol. 179, pp. 110008. Date of Electronic Publication: 2026 May 19. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| Ιατρικοί όροι (MeSH): | Lipid Metabolism*/drug effects , AMP-Activated Protein Kinases*/metabolism , Protein Serine-Threonine Kinases*/metabolism , Fatty Liver*/drug therapy , Fatty Liver*/metabolism , Euphorbia*/chemistry , Diterpenes*/pharmacology , Diterpenes*/chemistry , Diterpenes*/isolation & purification, Signal Transduction/drug effects ; Animals ; Mice ; AMP-Activated Protein Kinase Kinases ; Humans ; Male ; Mice, Inbred C57BL ; Molecular Structure ; Structure-Activity Relationship ; Dose-Response Relationship, Drug ; Cells, Cultured |
| Περίληψη: | Hepatic steatosis is a chronic progressive condition that leads to multiple severe liver disorders. However, current therapeutic options are limited for available drugs. Screening active natural products for curing hepatic steatosis provide novel chemical scaffolds for drug development and chemical probes to reveal novel mechanisms in the development of hepatic steatosis. Here, we established an in vitro cell model for measuring hepatic lipid content and screened a series of euphorane-type diterpenoids to identify active diterpenoids for decreasing hepatic lipids. Interestingly, among these diterpenoids, euphorbia factor L3 (EFL3) exhibited the most pronounced lipid-lowering activity, both in cultured hepatocytes and in HFD-induced mice with hepatic steatosis. Mechanistic studies demonstrated that EFL3 activated the LKB1-AMPK signaling pathway in hepatocytes, leading to downregulation of the lipogenic factors SREBP-1c, ACC1, and FASN, and leading to upregulation of fatty acid oxidation-related proteins SIRT1, PGC-1α, PPARα, and CPT1A. These changes improved cellular lipid metabolism and ultimately ameliorated hepatic steatosis in mice. In summary, this study supports the key role of LKB1-AMPK pathway in regulation of hepatic steatosis and reveals that EFL3 could be considered as a novel compound for drug development against hepatic steatosis. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| 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: Euphorbia factor L3; Hepatic steatosis; LKB1-AMPK; Lipid metabolism; Natural product |
| Substance Nomenclature: | EC 2.7.11.31 (AMP-Activated Protein Kinases) EC 2.7.11.1 (Protein Serine-Threonine Kinases) EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases) EC 2.7.11.1 (Stk11 protein, mouse) 0 (Diterpenes) EC 2.7.11.1 (STK11 protein, human) |
| Entry Date(s): | Date Created: 20260523 Date Completed: 20260613 Latest Revision: 20260613 |
| Update Code: | 20260613 |
| DOI: | 10.1016/j.bioorg.2026.110008 |
| PMID: | 42176359 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2026.110008 |