Evidence map›Paper›PMID 42374202›Full record

ArticleBMC gastroenterology2026

Bioactive folate attenuates valproic acid-induced NAFLD in female rats.

Hajra Ashraf, Tooba Asif, Fatima Baqir, Naila Naz

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Article in BMC gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Hajra AshrafDepartment of Biomedicine, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences & Technology, Islamabad, Pakistan.
Tooba AsifDepartment of Biomedicine, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences & Technology, Islamabad, Pakistan.
Fatima BaqirDepartment of Biomedicine, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences & Technology, Islamabad, Pakistan.
Naila NazDepartment of Biomedicine, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences & Technology, Islamabad, Pakistan. nnaz@asab.nust.edu.pk.ORCID https://orcid.org/0000-0002-8864-0250

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNonalcoholic fatty liver disease (NAFLD) is a key contributor to chronic liver diseases. It is defined as hepatic fat accumulation in ≥ 5% of hepatocytes in individuals with minimal or no alcohol consumption and no other identifiable causes of liver steatosis. Drug-induced hepatic toxicity is increasingly recognized as a key contributor to the development and progression of NAFLD. Among them, valproic acid (VPA), an antiepileptic drug, is well documented for inducing hepatic steatosis, in addition to interfering with folate metabolism and accelerating the progression of NAFLD. The current study distinctively evaluates the protective role of bioactive folate derivatives (folinic acid and 5-methyltetrahydrofolate) in a VPA-induced NAFLD rat model.

methodsAdult female Sprague Dawley rats were divided into three groups: control, diseased and treated. Liver function test, histopathological examination, gene expression analysis, and molecular docking were performed.

resultsLiver function tests indicated that the increase in alanine aminotransferase, alkaline phosphatase, and total bilirubin levels was highly significant in the diseased group, indicative of hepatic injury. Histopathological examination demonstrated severe steatosis in VPA-treated animals, which was significantly improved in the folate-treated group. The NAFLD Activity Score, a mild NAFLD was observed in the diseased group with a total score of 2. Gene expression studies showed high upregulation of HO-1 and pro-inflammatory cytokines TNF-α and IL-6 in the diseased group, whereas downregulation was observed in folate-treated rats. Furthermore, molecular docking studies indicated that folinic acid and 5mTHF showed high affinities for binding to KEAP1 protein, suggestive of activation of the Nrf2-KEAP1 antioxidant pathway.

conclusionsCollectively, our data provide significant evidence for the protective potential of bioactive folate supplementation in the amelioration of the VPA-induced liver injury through modulation of oxidative stress, inflammation, and lipid accumulation.

Indexed as

Folic AcidNon-alcoholic Fatty Liver DiseaseValproic AcidAlanine TransaminaseAnimalsAnticonvulsantsDisease Models, AnimalFemaleKelch-Like ECH-Associated Protein 1LiverLiver Function TestsMolecular Docking SimulationNF-E2-Related Factor 2Oxidative StressRatsRats, Sprague-DawleyAlanine TransaminaseAnticonvulsantsFolic AcidKEAP1 protein, ratKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2Tumor Necrosis Factor-alphaValproic AcidBioactive folatesDrug-induced liver injuryHepatic steatosisHepatoprotectionInflammationMolecular dockingNonalcoholic fatty liver diseaseNrf2-KEAP1 pathwayOxidative stressSodium valproate

Identifiers

PMID42374202
PMCPMC13584381

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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.