Evidence map›Paper›PMID 41463396›Full record

ArticleBiomolecules2025

Integrating Network Pharmacology, Molecular Docking, and Experimental Validation: Andrographolide Attenuates Acute Liver Injury via the NLRP3/Caspase-1/GSDMD-Mediated Pyroptosis Pathway.

Yankun Zhang, Shuanghui Liu, Xiaoxia Liang, Lizi Yin, Changliang He

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomolecules, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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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

2 citing papers in PubMed.

  1. Review
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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

5 authors.

Yankun ZhangDepartment of Clinical Veterinary, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Shuanghui LiuDepartment of Clinical Veterinary, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Xiaoxia LiangNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Lizi YinNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.ORCID 0000-0001-8893-9538
Changliang HeDepartment of Clinical Veterinary, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.ORCID 0000-0002-7717-5832

Funding

National Natural Science Foundation of China 32273047Natural Science Foundation of Sichuan Province 2024NSFSC0372
6 · The paper itself

Abstract

BACKGROUND/

objectivesAndrographolide (Andro), a natural diterpenoid lactone, possesses a wide range of pharmacological properties, including notable anti-inflammatory, antioxidant, antitumor, and immunomodulatory activities. Despite its acknowledged therapeutic promise, the exact protective mechanisms underlying its efficacy against acute liver injury (ALI) are still not fully understood. Consequently, determining the molecular mechanisms through which andrographolide alleviates ALI is of substantial scientific and clinical relevance.

methodsAndrographolide's potential targets and pharmacological mechanisms against liver injury were initially identified using network pharmacology and molecular docking. An acute liver injury (ALI) rat model was induced by intraperitoneal injection of lipopolysaccharide (LPS). The therapeutic efficacy of andrographolide in ALI was evaluated by examining liver histopathology, measuring liver function and oxidative stress markers, and quantifying pro-inflammatory cytokine levels. Meanwhile, the expression of key constituents along the NLRP3/caspase-1/GSDMD signaling axis was quantified using RT-qPCR and Western blotting. In parallel, the protective effect of andrographolide via the canonical NLRP3/caspase-1/GSDMD pyroptosis pathway was further examined in vitro using LPS-plus-ATP-stimulated rat hepatocyte BRL-3A cells.

resultsNetwork pharmacology analysis predicted that andrographolide (Andro) protects against liver injury mainly by targeting core regulators of pyroptosis. Molecular docking simulations further indicated stable binding interactions between Andro and key proteins involved in the pyroptotic pathway, such as NLRP3, ASC, GSDMD, and CASP1. These predictions were experimentally confirmed. Andro administration notably mitigated histopathological alterations, restored serum liver function indicators, lowered pro-inflammatory cytokine levels, and alleviated oxidative stress. Importantly, Andro substantially suppressed the expression of critical mediators along the pyroptosis signaling cascade.

conclusionsThis study demonstrates that andrographolide (Andro) ameliorates acute liver injury (ALI) by specifically inhibiting the NLRP3/Caspase-1/GSDMD-mediated pyroptosis pathway. By elucidating this underlying molecular mechanism, our work highlights Andro's potential as a novel and promising therapeutic candidate for ALI.

Indexed as

Caspase 1DiterpenesIntracellular Signaling Peptides and ProteinsNLR Family, Pyrin Domain-Containing 3 ProteinPyroptosisAnimalsChemical and Drug Induced Liver InjuryGasderminsLipopolysaccharidesLiverMaleMolecular Docking SimulationNetwork PharmacologyOxidative StressPhosphate-Binding ProteinsRatsandrographolideCaspase 1DiterpenesGasderminsGsdmd protein, ratIntracellular Signaling Peptides and ProteinsLipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratPhosphate-Binding Proteinsacute liver injuryandrographolidemolecular dockingnetwork pharmacologypyroptosis

Identifiers

PMID41463396
PMCPMC12730944

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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.