ArticleActa pharmacologica Sinica2021
Ursolic acid reduces hepatocellular apoptosis and alleviates alcohol-induced liver injury via irreversible inhibition of CASP3 in vivo.
Article in Acta pharmacologica Sinica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 57 citations in OpenAlex.
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- Bioactive plant and fungal metabolites in oral cancer: molecular mechanisms and translational potential.Frontiers in pharmacology · 2026Review
- Mechanistic Insights into the Metabolic Pathways and Neuroprotective Potential of Pentacyclic Triterpenoids: In-Depth Analysis of Betulin, Betulinic, and Ursolic Acids.Biomolecules · 2025Review
- Exploring the toxic mechanism of excessive intake of naringin on drug-induced liver injury using network toxicology and experiment validation strategy.BMC pharmacology & toxicology · 2025Article
- PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review).Molecular medicine reports · 2025Review
- Oxidative stress modulation in alcohol-related liver disease: From chinese botanical drugs to exercise-based interventions.Frontiers in pharmacology · 2025Review
- Palm Kernel Cake Extracts Obtained from the Combination of Bacterial Fermentation and Enzymic Hydrolysis Promote Swine Small Intestine IPEC-J2 Cell Proliferation and Alleviate LPS-Induced Inflammation In Vitro.Antioxidants (Basel, Switzerland) · 2024Article
- The Antitumor and Sorafenib-resistant Reversal Effects of Ursolic Acid on Hepatocellular Carcinoma via Targeting ING5.International journal of biological sciences · 2024Article
- Role of ursolic acid in preventing gastrointestinal cancer: recent trends and future perspectives.Frontiers in pharmacology · 2024Review
- Exploring the mechanism of JiGuCao capsule formula on treating hepatitis B virus infection via network pharmacology analysis andFrontiers in pharmacology · 2023Article
- 1-ACS omega · 2022Article
- Exploring the immunomodulatory effects and mechanisms of Xinjiang fermented camel milk-derived bioactive peptides based on network pharmacology and molecular docking.Frontiers in pharmacology · 2022Article
- Potential value and chemical characterization of gut microbiota derived nitrogen containing metabolites in feces from Periplaneta americana (L.) at different growth stages.Scientific reports · 2021Article
- The Potential Application of Chinese Medicine in Liver Diseases: A New Opportunity.Frontiers in pharmacology · 2021Review
- Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease.Frontiers in pharmacology · 2021Article
- Natural Compounds: A Potential Treatment for Alcoholic Liver Disease?Frontiers in pharmacology · 2021Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alcoholic liver disease (ALD) is one of the pathogenic factors of chronic liver disease with the highest clinical morbidity worldwide. Ursolic acid (UA), a pentacyclic terpenoid carboxylic acid, has shown many health benefits including antioxidative, anti-inflammatory, anticancer, and hepatoprotective activities. We previously found that UA was metabolized in vivo into epoxy-modified UA containing an epoxy electrophilic group and had the potential to react with nucleophilic groups. In this study we prepared an alkynyl-modified UA (AM-UA) probe for tracing and capturing the target protein of UA from liver in mice, then investigated the mode by which UA bound to its target in vivo. By conducting proteome identification and bioinformatics analysis, we identified caspase-3 (CASP3) as the primary target protein of UA associated with liver protection. Molecule docking analysis showed that the epoxy group of the UA metabolite reacted with Cys-163 of CASP3, forming a covalent bond with CASP3. The binding mode of the UA metabolites (UA, CM-UA, and EM-UA) was verified by biochemical evaluation, demonstrating that the epoxy group produced by metabolism played an important role in the inhibition of CASP3. In alcohol-treated HepG2 cells, pretreatment with the UA metabolite (10 μM) irreversibly inhibited CASP3 activities, and subsequently decreased the cleavage of PARP and cell apoptosis. Finally, pre-administration of UA (20-80 mg· kg
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