Evidence map›Paper›PMID 27369375›Full record

ArticleArchives of toxicology2017

Activation of the Nrf2 signaling pathway in usnic acid-induced toxicity in HepG2 cells.

Si Chen, Zhuhong Zhang, Tao Qing, Zhen Ren, Dianke Yu, Letha Couch, Baitang Ning, Nan Mei, Leming Shi, William H Tolleson and 1 more

Open access · greenAbstract read
In one paragraph

Article in Archives of toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
14.9field-weighted citation impact, top 2% 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

19 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Article
  3. Unassuming Lichens: Nature's Hidden Antimicrobial Warriors.International journal of molecular sciences · 2025
    Review
  4. Article
  5. Hepatotoxicity of usnic acid and underlying mechanisms.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025
    Review
  6. Article
  7. Review
  8. Herceptin induces ferroptosis and mitochondrial dysfunction in H9c2 cells.International journal of molecular medicine · 2022
    Article
  9. Toxicity of Usnic Acid: A Narrative Review.Journal of toxicology · 2022
    Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Genetic toxicity assessment using liver cell models: past, present, and future.Journal of toxicology and environmental health. Part B, Critical reviews · 2020
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Safety assessment of the dietary supplement OxyELITE™ Pro (New Formula) in inbred and outbred mouse strains.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2017
    Article
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

11 authors at 4 institutions in 2 countries.

Si ChenDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA), HFT-110, 3900 NCTR Road, Jefferson, AR, 72079, USA.
Zhuhong ZhangDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research/U.S. FDA, Jefferson, AR, 72079, USA.
Tao QingSchool of Pharmacy, School of Life Sciences, Fudan-Zhangjiang Center for Clinical Genomics and Zhanjiang Center for Translational Medicine, Fudan University, Shanghai, 200438, China.
Zhen RenDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA), HFT-110, 3900 NCTR Road, Jefferson, AR, 72079, USA.
Dianke YuDivision of Systems Biology, National Center for Toxicological Research/U.S. FDA, Jefferson, AR, 72079, USA.
Letha CouchDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA), HFT-110, 3900 NCTR Road, Jefferson, AR, 72079, USA.
Baitang NingDivision of Systems Biology, National Center for Toxicological Research/U.S. FDA, Jefferson, AR, 72079, USA.
Nan MeiDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research/U.S. FDA, Jefferson, AR, 72079, USA.
Leming ShiSchool of Pharmacy, School of Life Sciences, Fudan-Zhangjiang Center for Clinical Genomics and Zhanjiang Center for Translational Medicine, Fudan University, Shanghai, 200438, China.
William H TollesonDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA), HFT-110, 3900 NCTR Road, Jefferson, AR, 72079, USA.
Lei GuoDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA), HFT-110, 3900 NCTR Road, Jefferson, AR, 72079, USA. lei.guo@fda.hhs.gov.
National Center for Toxicological Research · USUnited States Food and Drug Administration · USFudan University · CNTianjin Medical University General Hospital · CN

Funding

Protective behavioral strategies and mental health: Reducing alcohol-related riskR21AA020104 · NIAAA · LOYOLA MARYMOUNT UNIVERSITY · PI LABRIE, JOSEPH W. · 2010 to 2011
$367k
Intramural FDA HHS FD999999NIAAA NIH HHS R21 AA020104
6 · The paper itself

Abstract

Many usnic acid-containing dietary supplements have been marketed as weight loss agents, although severe hepatotoxicity and acute liver failure have been associated with their overuse. Our previous mechanistic studies revealed that autophagy, disturbance of calcium homeostasis, and ER stress are involved in usnic acid-induced toxicity. In this study, we investigated the role of oxidative stress and the Nrf2 signaling pathway in usnic acid-induced toxicity in HepG2 cells. We found that a 24-h treatment with usnic acid caused DNA damage and S-phase cell cycle arrest in a concentration-dependent manner. Usnic acid also triggered oxidative stress as demonstrated by increased reactive oxygen species generation and glutathione depletion. Short-term treatment (6 h) with usnic acid significantly increased the protein level for Nrf2 (nuclear factor erythroid 2-related factor 2), promoted Nrf2 translocation to the nucleus, up-regulated antioxidant response element (ARE)-luciferase reporter activity, and induced the expression of Nrf2-regulated targets, including glutathione reductase, glutathione S-transferase, and NAD(P)H quinone oxidoreductase-1 (NQO1). Furthermore, knockdown of Nrf2 with shRNA potentiated usnic acid-induced DNA damage and cytotoxicity. Taken together, our results show that usnic acid causes cell cycle dysregulation, DNA damage, and oxidative stress and that the Nrf2 signaling pathway is activated in usnic acid-induced cytotoxicity.

Indexed as

Antioxidant Response ElementsBenzofuransDNA DamageDose-Response Relationship, DrugGene Expression RegulationGlutathioneHep G2 CellsHumansNF-E2-Related Factor 2Reactive Oxygen SpeciesSignal TransductionS Phase Cell Cycle CheckpointsBenzofuransGlutathioneNFE2L2 protein, humanNF-E2-Related Factor 2Reactive Oxygen Speciesusnic acidLiver toxicityNrf2 pathwayOxidative stressUsnic acid

Identifiers

PMID27369375
PMCPMC5727582
OpenAlexW2473076159

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.