ArticleEndocrinology, diabetes & metabolism2021
Oxy210, a novel inhibitor of hedgehog and TGF-β signalling, ameliorates hepatic fibrosis and hypercholesterolemia in mice.
Article in Endocrinology, diabetes & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Cell differentiation-related signaling pathways: biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
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- Therapeutic Targets and Approaches to Manage Inflammation of NAFLD.Biomedicines · 2025Review
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- Article
- Profiling of differentially expressed MicroRNAs in familial hypercholesterolemia via direct hybridization.Non-coding RNA research · 2024Article
- A two-way street - cellular metabolism and myofibroblast contraction.NPJ Regenerative medicine · 2024Review
- Multifunctional roles of inflammation and its causative factors in primary liver cancer: A literature review.World journal of hepatology · 2023Review
- Circulating indian hedgehog is a marker of the hepatocyte-TAZ pathway in experimental NASH and is elevated in humans with NASH.JHEP reports : innovation in hepatology · 2023Article
- Anti-miR-96 and Hh pathway inhibitor MDB5 synergistically ameliorate alcohol-associated liver injury in mice.Biomaterials · 2023Article
- Oxy210, a Semi-Synthetic Oxysterol, Inhibits Profibrotic Signaling in Cellular Models of Lung and Kidney Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH).Signal transduction and targeted therapy · 2022Review
- Oxysterol derivatives Oxy186 and Oxy210 inhibit WNT signaling in non-small cell lung cancer.Cell & bioscience · 2022Article
- Oxy210, a Semi-Synthetic Oxysterol, Exerts Anti-Inflammatory Effects in Macrophages via Inhibition of Toll-like Receptor (TLR) 4 and TLR2 Signaling and Modulation of Macrophage Polarization.International journal of molecular sciences · 2022Article
- Diagnostic and therapeutic strategies for non-alcoholic fatty liver disease.Frontiers in pharmacology · 2022Review
- Oxy210, a novel inhibitor of hedgehog and TGF-β signalling, ameliorates hepatic fibrosis and hypercholesterolemia in mice.Endocrinology, diabetes & metabolism · 2021Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
aimsNon-alcoholic steatohepatitis (NASH) is associated with increased overall morbidity and mortality in non-alcoholic fatty liver disease (NAFLD) patients. Liver fibrosis is the strongest prognostic factor for clinical outcomes, liver-related mortality and liver transplantation. Currently, no single therapy or medication for NASH has been approved by the U.S. Food and Drug Administration (FDA). Oxy210, an oxysterol derivative, displays the unique property of antagonizing both Hedgehog (Hh) and transforming growth factor-beta (TGF-β) signalling in primary human hepatic stellate cells (HSC). We hypothesized that inhibition of both Hh and TGF-β signalling by Oxy210 could reduce hepatic fibrosis in NASH. In this study, we examined the therapeutic potential of Oxy210 on NASH in vivo.
methodsWe examined the effect of Oxy210 treatment on Hh and TGF-β pathways in HSC. The efficacy of Oxy210 on liver fibrosis was tested in a 'humanized' hyperlipidemic mouse model of NASH that has high relevance to human pathology. APPROACH AND
resultsWe show that Oxy210 inhibits both Hh and TGF-β pathways in human HSC and attenuates baseline and TGF-β-induced expression of pro-fibrotic genes in vitro. Oral delivery of Oxy210 in food resulted in significant liver exposure and significantly reduced hepatic fibrosis in mice over the course of the 16-week study with no apparent safety issues. Additionally, we observed several benefits related to NASH phenotype: (a) reduced plasma pro-inflammatory cytokine and the corresponding hepatic gene expression; (b) reduced pro-fibrotic cytokine and inflammasome gene expression in the liver; (c) reduced apoptosis in the liver; (d) reduced hepatic unesterified cholesterol accumulation; and (e) reduced plasma total and unesterified cholesterol levels.
conclusionsOxy210 effectively ameliorated hepatic fibrosis and inflammation and improved hypercholesterolemia in mice. Our findings suggest that Oxy210 and related analogues are a new class of drug candidates that may serve as potential therapeutics candidates for NASH.
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