ArticleAntiviral research2017
Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells.
Article in Antiviral research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Advancing Antiviral Design: Integrating Natural Products, Computation and Targeted Delivery.Chemical biology & drug design · 2026Review
- Modulating nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in liver-brain axis disorders.World journal of psychiatry · 2025Review
- Evaluation of Celastrol Antiviral Activity Against Equid Alphaherpesvirus Type 8 Infection.Viruses · 2025Article
- Effects of celastrol on the heart and liver galaninergic system expression in a mouse model of Western-type diet-induced obesity and metabolic dysfunction-associated steatotic liver disease and steatohepatitis.Frontiers in pharmacology · 2025Article
- The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections.International journal of molecular sciences · 2024Review
- Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways.Journal of virology · 2024Article
- Review
- The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections.Pathogens (Basel, Switzerland) · 2023Review
- Celastrol attenuates human parvovirus B19 NS1‑induced NLRP3 inflammasome activation in macrophages.Molecular medicine reports · 2023Article
- Celastrol attenuates hepatitis C virus translation and inflammatory response in mice by suppressing heat shock protein 90β.Acta pharmacologica Sinica · 2023Article
- In vitro activity of celastrol in combination with thymol against carbapenem-resistant Klebsiella pneumoniae isolates.The Journal of antibiotics · 2022Article
- Balanced cytokine upregulation by diluted ethanolic extract ofBulletin of the National Research Centre · 2022Article
- The Age-Specific Features and Clinical Significance of NRF2 and MAPK10 Expression in HCC Patients.International journal of general medicine · 2022Article
- The Nrf2 Pathway in Liver Diseases.Frontiers in cell and developmental biology · 2022Review
- Celastrol: An Update on Its Hepatoprotective Properties and the Linked Molecular Mechanisms.Frontiers in pharmacology · 2022Review
- Article
- Research progress on the antiviral activities of natural products and their derivatives: Structure-activity relationships.Frontiers in chemistry · 2022Review
- Antimicrobial Activity and Mode of Action of Celastrol, a Nortriterpen Quinone Isolated from Natural Sources.Foods (Basel, Switzerland) · 2021Article
- Bioactive Terpenes and Their Derivatives as Potential SARS-CoV-2 Proteases Inhibitors from Molecular Modeling Studies.Biomolecules · 2021Article
- Anti-SARS-CoV-2 Natural Products as Potentially Therapeutic Agents.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeCelastrol, a quinone methide triterpene isolated from the root extracts of Tripterygium wilfordii, can greatly induce the gene expression activity of heme oxygenase-1 (HO-1) to achieve disease prevention and control. HO-1 induction was recently shown to result in anti-HCV activity by inducing type I interferon and inhibiting hepatitis C virus (HCV) NS3/4A protease activity. The aim of the present study is to evaluate the anti-HCV activity of celastrol and characterize its mechanism of inhibition.
methodsThe anti-HCV activity of celastrol was evaluated using the HCV subgenomic replicon and HCVcc infection systems. The anti-HCV mechanism of celastrol targeting HO-1 expression was clarified using specific inhibitors against several signaling pathways. The transcriptional regulation of celastrol on target gene expression was determined using promoter-based reporter activity assay. The synergistic effect of celastrol and a numbers of clinically used anti-HCV drugs was determined via a drug combination assay.
resultsCelastrol inhibited HCV replication in both the HCV subgenomic and HCVcc infection systems with EC50 values of 0.37 ± 0.022 and 0.43 ± 0.019 μM, respectively. Celastrol-induced heme oxygenase 1 (HO-1) expression promoted antiviral interferon responses and inhibition of NS3/4A protease activity, thereby blocking HCV replication. These antiviral effects were abrogated by treatment with the HO-1-specific inhibitor SnMP or silencing of HO-1 expression by transfection of shRNA, which indicates that HO-1 induction contributes to the anti-HCV activity of celastrol. JNK mitogen-activated protein kinase and nuclear factor erythroid 2-related factor 2 (Nrf2) were confirmed to be involved in the inductive effect of celastrol on HO-1 expression. Celastrol exhibited synergistic effects in combination with interferon-alpha, the NS5A inhibitor daclatasvir, and the NS5B inhibitor sofosbuvir.
conclusionCelastrol can serve as a potential supplement for blocking HCV replication. Targeting the JNK/Nrf2/HO-1 axis presents a promising strategy against HCV infection.
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