Evidence map›Paper›PMID 25816210›Full record

ArticlePloS one2015

Gallic acid induces necroptosis via TNF-α signaling pathway in activated hepatic stellate cells.

Ya Ju Chang, Shih Lan Hsu, Yi Ting Liu, Yu Hsuan Lin, Ming Hui Lin, Shu Jung Huang, Ja-an Annie Ho, Li-Chen Wu

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
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

28 citing papers in PubMed, 54 citations in OpenAlex.

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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

8 authors at 3 institutions in 1 country.

Ya Ju ChangDepartment of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.
Shih Lan HsuDepartment of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Yi Ting LiuDepartment of Applied Chemistry, National Chi Nan University, Puli, Taiwan.
Yu Hsuan LinDepartment of Applied Chemistry, National Chi Nan University, Puli, Taiwan.
Ming Hui LinDepartment of Applied Chemistry, National Chi Nan University, Puli, Taiwan.
Shu Jung HuangDepartment of Applied Chemistry, National Chi Nan University, Puli, Taiwan.
Ja-an Annie HoDepartment of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.
Li-Chen WuDepartment of Applied Chemistry, National Chi Nan University, Puli, Taiwan.
National Chi Nan University · TWNational Taiwan University · TWTaichung Veterans General Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gallic acid (3, 4, 5-trihydroxybenzoic acid, GA), a natural phenolic acid widely found in gallnuts, tea leaves and various fruits, possesses several bioactivities against inflammation, oxidation, and carcinogenicity. The beneficial effect of GA on the reduction of animal hepatofibrosis has been indicated due to its antioxidative property. However, the cytotoxicity of GA autoxidation causing cell death has also been reported. Herein, we postulated that GA might target activated hepatic stellate cells (aHSCs), the cell type responsible for hepatofibrosis, to mitigate the process of fibrosis. The molecular cytotoxic mechanisms that GA exerted on aHSCs were then analyzed. The results indicated that GA elicited aHSC programmed cell death through TNF-α-mediated necroptosis. GA induced significant oxidative stress through the suppression of catalase activity and the depletion of glutathione (GSH). Elevated oxidative stress triggered the production of TNF-α facilitating the undergoing of necroptosis through the up-regulation of key necroptotic regulatory proteins TRADD and receptor-interacting protein 3 (RIP3), and the inactivation of caspase-8. Calmodulin and calpain-1 activation were engaged, which promoted subsequent lysosomal membrane permeabilization (LMP). The TNF-α antagonist (SPD-304) and the RIP1 inhibitor (necrostatin-1, Nec-1) confirmed GA-induced TNFR1-mediated necroptosis. The inhibition of RIP1 by Nec-1 diverted the cell death from necroptosis to apoptosis, as the activation of caspase 3 and the increase of cytochrome c. Collectively, this is the first report indicating that GA induces TNF signaling-triggered necroptosis in aHSCs, which may offer an alternative strategy for the amelioration of liver fibrosis.

Indexed as

Oxidative StressAnimalsApoptosisBlotting, WesternCaspasesCell CycleCell ProliferationCells, CulturedChromansGallic AcidHepatic Stellate CellsIndolesLipid PeroxidationNecrosisProtein Serine-Threonine KinasesRatsCaspasesChromansGallic AcidIndolesProtein Serine-Threonine KinasesReactive Oxygen SpeciesReceptor-Interacting Protein Serine-Threonine KinasesReceptors, Tumor Necrosis Factor, Type IRIPK1 protein, ratSPD-304TNF protein, humanTumor Necrosis Factor-alpha

Identifiers

PMID25816210
PMCPMC4376672
OpenAlexW2063729702

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Registered trials

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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.