ArticlePharmaceuticals (Basel, Switzerland)2022
Paeonol Protects against Methotrexate Hepatotoxicity by Repressing Oxidative Stress, Inflammation, and Apoptosis-The Role of Drug Efflux Transporters.
Article in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Dapagliflozin attenuates methotrexate-induced hepatorenal toxicity in rats: insights into oxidative stress, inflammation, autophagy and apoptosis.Molecular and cellular biochemistry · 2026Article
- Paeonol as a Multi-Target Therapy for Neurological Disorders: Mechanistic Insights Into Neuroprotection.Immunity, inflammation and disease · 2026Review
- Fondaparinux attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and inflammatory signaling via the TLR4/NLRP3 and NF-κB/IL-1β/MCP-1 pathways.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
- L-carnitine protects against methotrexate-induced hepatotoxicity via regulation of apoptosis and metabolic pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Molecular Mechanisms Underlying the Anti-Tumor Activity of Lotus-Derived Alkaloids in Breast Cancer.Molecules (Basel, Switzerland) · 2026Article
- Mitigative effects of Otilonium Bromide on methotrexate-induced hepatic damage in rats.BMC research notes · 2026Article
- Functional roles and regulatory mechanisms of paeonol in the treatment of liver disease.Natural products and bioprospecting · 2026Review
- Apple Seed Extract in Cancer Treatment: Assessing Its Effects on Liver Damage and Recovery.Current issues in molecular biology · 2026Article
- Study of the Stability and Anti-Inflammatory Activity of Paeonol-Oleanolic Acid Liposomes by Microfluidic Technology.Foods (Basel, Switzerland) · 2025Article
- In vivo and in silico studies on the potential role of garden cress oil in attenuating methotrexate-induced inflammation and apoptosis in liver.Scientific reports · 2025Article
- Based on the Dual Pathway of Interaction-Mediated NF-κB in Cell Apoptosis and Immune Inflammation to Study the Effect of Danzhi Xiaoyao Powder on the Learning and Cognitive Ability of AD Model Rats.Degenerative neurological and neuromuscular disease · 2025Article
- Integrative RNA-seq and LASSO-COX analysis reveal Paeonol's key target gene in proliferation suppression and apoptosis-induced in cervical cancer.Frontiers in pharmacology · 2025Article
- Silibinin's Effects against Methotrexate-Induced Hepatotoxicity in Adjuvant-Induced Arthritis Rat Model.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Regulation of P-Glycoprotein during Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024Review
- Nitazoxanide mitigates methotrexate hepatotoxicity in rats: role in inhibiting apoptosis and regulating endoplasmic reticulum stress.Frontiers in pharmacology · 2024Article
- DNA damage caused by chemotherapy has duality, and traditional Chinese medicine may be a better choice to reduce its toxicity.Frontiers in pharmacology · 2024Review
- Potential Hepatoprotective Effects ofAntioxidants (Basel, Switzerland) · 2023Article
- Pharmacological effects and mechanisms of paeonol on antitumor and prevention of side effects of cancer therapy.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Methotrexate (MTX) is an effective chemotherapeutic agent against a wide range of tumors and autoimmune diseases; however, hepatotoxicity limits its clinical use. Oxidative stress and inflammation have been implicated in the pathogenesis of MTX-induced hepatotoxicity. Paeonol is a natural phenolic compound reported for its antioxidant and anti-inflammatory properties. The current study aimed to investigate the protective effect of paeonol against MTX-induced hepatotoxicity in rats and various mechanisms that underlie this postulated effect. Paeonol was administered orally in a dose of 100 mg/kg, alone or along with MTX, for 10 days. Hepatotoxicity was induced via a single intraperitoneal dose of MTX (20 mg/kg) on day 5 of the experiment. Concomitant administration of paeonol with MTX significantly ameliorated distorted hepatic function and histological structure, restored hepatic oxidative stress parameters (MDA, NO, and SOD), and combated inflammatory response (iNOS and TNF-α). Additionally, paeonol enhanced cell proliferation and survival, evidenced by upregulating the proliferating cell nuclear antigen (PCNA) and suppressing apoptosis and the disposition of collagen fibers in rat livers treated with MTX. Importantly, paeonol upregulated the drug efflux transporters, namely P-glycoprotein (P-gp) and the multidrug resistance-associated protein 2 (Mrp-2) in MTX-treated rats. In conclusion, paeonol offered a potent protective effect against MTX-induced hepatotoxicity through suppressing oxidative stress, inflammation, fibrosis, and apoptosis pathways, along with P-gp and Mrp-2 upregulation.
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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.