ArticleInternational journal of molecular sciences2022
Punicalagin Protects against the Development of Methotrexate-Induced Hepatotoxicity in Mice via Activating Nrf2 Signaling and Decreasing Oxidative Stress, Inflammation, and Cell Death.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Piribedil attenuates methotrexate-induced nephrotoxicity in rats: associated changes in miR-205/EGLN2, Nrf2, and PERK/ATF4/CHOP-related stress responses.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Loureirin B Attenuates Methotrexate-Induced Liver Injury Associated with Oxidative Stress, SIRT1 Alterations, and TGF-β/SMAD3-Related Profibrotic Responses.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Pharmacological Mechanisms of Phytochemicals and Pharmaceutical Agents in Protecting Against Methotrexate-Induced Liver Injury.Oxidative medicine and cellular longevity · 2026Review
- Comparative effects of dietary pomegranate peel andFrontiers in nutrition · 2026Article
- Balancing efficacy and hepatotoxicity: a comprehensive review of oral medications in psoriasis management.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The Protective Effect of Phenolic Acids on Liver Disease: A Review of Possible Mechanisms.Antioxidants (Basel, Switzerland) · 2025Review
- Modulation of AMPK by esomeprazole and canagliflozin mitigates methotrexate-induced hepatotoxicity: involvement of MAPK/JNK/ERK, JAK1/STAT3, and PI3K/Akt signaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Nitrate protects against methotrexate-induced liver injury by activating Wnt/β-catenin Signaling in mice.Toxicology research · 2025Article
- Dabigatran attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and the NF-kB/IL-1β/MCP-1 and TLR4/NLRP3 signaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Repositioning Perindopril for Mitigation of Methotrexate-Induced Hepatotoxicity in Rats.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The role of Juniperus Macrocarpa extract as anti-inflammatory and antioxidant on methotrexate-induced acute liver injury in rat model.F1000Research · 2025Article
- Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity-a review of literature evidence.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Review
- Punicalagin alleviates the hyperproliferation of keratinocytes in psoriasis through inhibiting SKP2 expression.Journal of natural medicines · 2023Article
- Punicalagin relieves lipotoxic injuries on pancreatic β-cells via regulating the oxidative stress and endoplasmic reticulum stress-mediated apoptosis.In vitro cellular & developmental biology. Animal · 2023Article
- A standardized pomegranate fruit extract ameliorates thioacetamide-induced liver fibrosis in rats via AGE-RAGE-ROS signaling.Heliyon · 2023Article
- Role of Plant-Derived Compounds in the Molecular Pathways Related to Inflammation.International journal of molecular sciences · 2023Review
- Antibacterial and antiviral properties of punicalagin (Review).Medicine internationalReview
- Involvement of NOD1/NF-κB/MAPK pathway in the protective effect of procyanidin B2 against methotrexate-induced nephrotoxicity.Science progressArticle
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
Despite its effectiveness in treating inflammatory diseases and various malignancies, methotrexate (MTX) is well known to cause hepatotoxicity, which involves increased oxidative stress and inflammation, limiting its clinical use. Herein, we looked into the effect of punicalagin (PU), a polyphenolic molecule having a variety of health-promoting attributes, on MTX-induced hepatotoxicity in mice. PU (25 and 50 mg/kg/day) was given orally to the mice for 10 days, while a single dose of MTX (20 mg/kg) was injected intraperitoneally (i.p.) at day 7. The MTX-induced liver damage was demonstrated by remarkably higher transaminases (ALT and AST), ALP, and LDH, as well as significant histological alterations in hepatic tissues. MTX-injected mice also demonstrated increases in hepatic oxidative stress markers, including malondialdehyde (MDA) and nitric oxide (NO), with a concordant drop in glutathione (GSH) content and superoxide dismutase (SOD) and catalase (CAT) activities. PU significantly attenuated the MTX-induced serum transaminases, ALP and LDH elevations, and hepatic oxidative stress measures and boosted antioxidant defenses in the liver. Moreover, the liver of MTX-treated mice showed increases in NF-κB p65 expression, pro-inflammatory cytokine (IL-6 and TNF-α) levels, and pro-apoptotic protein (caspase-3 and Bax) expression, whereas Bcl-2 and Nrf2 expressions were reduced, which were all attenuated by PU treatment. Collectively, PU inhibits oxidative damage, inflammation, and apoptosis and upregulates Nrf2 in the liver of MTX-induced mice. Thus, these findings suggest that PU may have great therapeutic potential for the prevention of MTX-induced hepatotoxicity, pending further exploration in upcoming studies.
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Registered trials
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