Evidence map›Paper›PMID 39229978›Full record

ArticleCurrent computer-aided drug design2025

Mechanisms Underlying the Protective Effects of Obeticholic Acid-activated FXR in Valproic Acid-induced Hepatotoxicity

Ya'nan Chen, Jingkai Zhou, Shansen Xu, Lei Wang

Abstract read
PubMed Publisher
In one paragraph

Article in Current computer-aided drug design, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Ya'nan ChenDepartment of Pharmacy, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, PR China.ORCID 0000-0003-2978-8308
Jingkai ZhouDepartment of Immuno-Oncology, Beckman Research Institute City of Hope National Medical Center, Duarte CA, 91010, USA.ORCID 0000-0002-9867-3486
Shansen XuDepartment of Clinical Pharmacology, Jiangsu Simcere Pharmaceutical Co., Ltd, Nanjing, 210042, PR China.ORCID 0000-0002-2624-9192
Lei WangDepartment of Pharmacy, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, PR China.

Funding

Natural Science Foundation of Jiangsu Province of China Grant No. BK20210003The Hospital Pharmaceutical Research Fund of Nanjing Pharmaceutical Association Grant No. 2021YX031The Hospital Science and Technology Development Fund Grant No. ZJ202105
6 · The paper itself

Abstract

backgroundValproic acid (VPA)-induced hepatotoxicity is among the most common and severe adverse drug reactions, limiting its clinical application. Recent studies have suggested that activating the farnesoid X receptor (FXR) could be a promising therapeutic approach to alleviate VPA-induced hepatotoxicity; however, related research remains limited.

objectivesThis study aims to comprehensively investigate the mechanisms underlying FXR activation by obeticholic acid (OCA) for the treatment of VPA-induced hepatotoxicity.

methodsNetwork pharmacology was performed to identify potential targets and pathways underlying the amelioration of VPA-induced hepatotoxicity by OCA. The identified pathways were validated through GEO data analysis, and the affinities between OCA and potential key targets were predicted using molecular docking as well as molecular dynamics simulations.

resultsA total of 462 targets associated with VPA-induced hepatotoxicity and 288 targets of OCA were identified, with 81 shared targets. KEGG pathway and GO enrichment analysis indicated that the effect of OCA on VPA-induced hepatotoxicity primarily involved lipid metabolism, as well as oxidative stress and inflammation. The results from GEO data analysis, molecular docking, and molecular dynamics simulations revealed a close association between bile secretion, the PPAR signaling pathway, and the treatment of VPA-induced hepatotoxicity by OCA.

conclusionOur findings suggest that OCA exhibits potential therapeutic efficacy against VPAinduced hepatotoxicity through multiple targets and pathways, thereby highlighting the therapeutic potential of FXR as a target for treating VPA-induced hepatotoxicity.

Indexed as

Chemical and Drug Induced Liver InjuryChenodeoxycholic AcidReceptors, Cytoplasmic and NuclearValproic AcidHumansMolecular Docking SimulationMolecular Dynamics SimulationNetwork PharmacologyChenodeoxycholic Acidobeticholic acidReceptors, Cytoplasmic and NuclearValproic Acidfarnesoid X receptorhepatotoxicitymolecular dockingmolecular dynamics simulations.network pharmacologyobeticholic acidValproic acid

Identifiers

PMID39229978

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.