ArticleBritish journal of pharmacology2020
Costunolide represses hepatic fibrosis through WW domain-containing protein 2-mediated Notch3 degradation.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 64 citations in OpenAlex.
- A tale of dual role: HECT‑type E3 ubiquitin ligase mechanisms in liver diseases (Review).International journal of molecular medicine · 2026Review
- How to efficiently establish animal models of cholangiocarcinoma: challenges and inspiration.Medical review (2021) · 2026Review
- Overexpression ofTranslational lung cancer research · 2025Article
- Chikusetsusaponin IVa targeted YAP as an inhibitor to attenuate liver fibrosis and hepatic stellate cell activation.Chinese medicine · 2025Article
- PPM1G-mediated TBL1X mRNA splicing promotes cell migration in hepatocellular carcinoma.Cancer science · 2025Article
- PPM1G and its diagnostic, prognostic and therapeutic potential in HCC (Review).International journal of oncology · 2024Review
- Myofibrillogenesis Regulator-1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin-Protein Ligase Itchy Homolog in the Metastasis of Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PPM1G regulates hepatic ischemia/reperfusion injury through STING-mediated inflammatory pathways in macrophages.Immunity, inflammation and disease · 2024Article
- Prognostic and immunological potential of PPM1G in lung adenocarcinoma.Molecular medicine reports · 2023Article
- Costunolide alleviated DDC induced ductular reaction and inflammatory response in murine model of cholestatic liver disease.Journal of traditional and complementary medicine · 2023Article
- Liver Fibrosis Resolution: From Molecular Mechanisms to Therapeutic Opportunities.International journal of molecular sciences · 2023Review
- Therapeutic Effect of Costunolide in Autoimmune Hepatitis: Network Pharmacology and Experimental Validation.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Costunolide prevents renal ischemia-reperfusion injury in rats by reducing autophagy, apoptosis, inflammation, and DNA damage.Iranian journal of basic medical sciences · 2023Article
- E3 Ubiquitin Ligase Regulators of Notch Receptor Endocytosis: From Flies to Humans.Biomolecules · 2022Review
- High expression of PPM1G is associated with the progression and poor prognosis of hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2022Article
- The Cao-Xiang-Wei-Kang formula attenuates the progression of experimental colitis by restoring the homeostasis of the microbiome and suppressing inflammation.Frontiers in pharmacology · 2022Article
- Article
- Costunolide Loaded in pH-Responsive Mesoporous Silica Nanoparticles for Increased Stability and an Enhanced Anti-Fibrotic Effect.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells.International journal of molecular sciences · 2021Article
- Article
Corrections and comments
- Erratum issuedCORRECTION.2020
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
background and purposeThis study investigates the antifibrotic activities and potential mechanisms of costunolide (COS), a natural sesquiterpene compound. EXPERIMENTAL APPROACH: Rats subjected to bile duct ligation and mice challenged with CCl KEY
resultsIn animals, COS administration attenuated hepatic histopathological injury and collagen accumulation and reduced the expression of fibrogenic genes. COS time- and dose-dependently suppressed the levels of fibrotic markers in LX-2 cells and mouse pHSCs. Mechanistic studies showed COS destabilized Notch3 and subsequently inhibited the Notch3-HES1 pathway, thus inhibiting HSC activation. Furthermore, COS blocked the WW domain-containing protein 2 (WWP2)/protein phosphatase 1G (PPM1G) interaction and enhanced the effect of WWP2 on Notch3 degradation. CONCLUSIONS AND IMPLICATIONS: COS exerted potent antifibrotic effects in vitro and in vivo by disrupting the WWP2/PPM1G complex, promoting Notch3 degradation and inhibiting the Notch3/HES1 pathway. This indicates that COS may be a potential therapeutic candidate for the treatment of liver fibrosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.