Evidence map›Paper›PMID 42021414›Full record

ArticleBMC pharmacology & toxicology2026

Integration of multi-omics and network toxicology reveals TLR4-mediated nephrotoxicity induced by arecoline.

Jixiang Yuan, Lichen Chen, Xilong Wang, Zhibin Jiang, Dian Jin, Yongheng Bai, Xiaodong Pan, Yifu Li, Feihong Lin, Yong Cai

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In one paragraph

Article in BMC pharmacology & toxicology, 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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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Jixiang Yuan *Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Lichen Chen *Urology Centre, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China.
Xilong Wang *Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Zhibin JiangDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Dian JinDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Yongheng BaiZhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325035, China.
Xiaodong PanDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Yifu LiDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Feihong LinShanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China. linfeihong20212021@163.com.
Yong CaiDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. yorkcai@126.com.

Funding

Natural Science Foundation of Zhejiang Province, China LY21H050005Wenzhou Municipal Science and Technology Plan Project as well as funding from Huadong Medicine Co. Y20220116Youth Eagle Talented Cultivation Project of Shanghai Pulmonary Hospital No.Fkcy2404
6 · The paper itself

Abstract

backgroundArecoline, the primary alkaloid in areca nut, induces renal injury, yet its underlying molecular mechanisms remain poorly understood. This study aimed to identify arecoline’s molecular targets and elucidate the subsequent pathological signaling cascade in renal cells.

methodsWe integrated network toxicology, molecular docking, and molecular dynamics (MD) simulations to predict arecoline’s targets. In vitro validation in human kidney (HK-2) cells assessed target engagement via a cellular thermal shift assay (CETSA). Downstream signaling, inflammatory, and fibrotic markers were evaluated using Western blotting, ELISA, and immunofluorescence.

resultsComputational models predicted a stable arecoline-Toll-like receptor 4 (TLR4) complex. CETSA demonstrated that arecoline enhanced TLR4 thermal stability in HK-2 cells, strongly indicating target engagement. This binding activated the PI3K/AKT/NF-κB signaling pathway. Consequently, arecoline induced NF-κB-dependent upregulation of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), elevated the renal injury marker KIM-1, and promoted the accumulation of fibrotic proteins (α-SMA, Collagen III).

conclusionsArecoline instigates nephrotoxicity by targeting TLR4 and activating the PI3K/AKT/NF-κB axis, driving an inflammatory and fibrotic phenotype in renal tubular cells. The arecoline-TLR4 interaction represents a critical event in areca nut-associated nephropathy, offering a novel therapeutic target.

Indexed as

ArecolineKidney DiseasesToll-Like Receptor 4Cell LineCytokinesHumansKidneyMolecular Docking SimulationMolecular Dynamics SimulationMultiomicsNF-kappa BSignal TransductionArecolineCytokinesNF-kappa BTLR4 protein, humanToll-Like Receptor 4ArecolineMolecular dockingMolecular dynamics simulationNephrotoxicityNetwork toxicologyRenal injury

Identifiers

PMID42021414
PMCPMC13244984

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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.