Evidence map›Paper›PMID 25969626›Full record

ArticleMediators of inflammation2015

Punicalagin Induces Nrf2/HO-1 Expression via Upregulation of PI3K/AKT Pathway and Inhibits LPS-Induced Oxidative Stress in RAW264.7 Macrophages.

Xiaolong Xu, Hongquan Li, Xiaolin Hou, Deyin Li, Shasha He, Changrong Wan, Peng Yin, Mingjiang Liu, Fenghua Liu, Jianqin Xu

Open access · goldAbstract read
In one paragraph

Article in Mediators of inflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 1 pooled it
11.7field-weighted citation impact, top 1% 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

70 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Anti-Inflammatory Mechanisms ofJournal of microbiology and biotechnology · 2025
    Article
  5. Nrf2 mediated signaling axis in sepsis-induced cardiomyopathy: potential Pharmacological receptor.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Anti-Inflammatory Activity of BiotransformedJournal of microbiology and biotechnology · 2024
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

10 more citing papers are in PubMed but not listed here.

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

10 authors at 4 institutions in 2 countries.

Xiaolong XuCAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, China.
Hongquan LiCollege of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
Xiaolin HouCollege of Animal Science and Technology, Beijing University of Agriculture (BUA), Beijing 102206, China.
Deyin LiCollege of Animal Science and Technology, Beijing University of Agriculture (BUA), Beijing 102206, China.
Shasha HeCAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, China.
Changrong WanCAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, China.
Peng YinCAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, China.ORCID 0000-0002-9824-4964
Mingjiang LiuCAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, China.
Fenghua LiuCollege of Animal Science and Technology, Beijing University of Agriculture (BUA), Beijing 102206, China ; Beijing Key Laboratory for Dairy Cow Nutrition, Beijing 102206, China.
Jianqin XuCAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, China.ORCID 0000-0002-7941-573X
China Agricultural University · CNBeijing University of Agriculture · CNDairy Management · USShanxi Agricultural University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Reactive oxygen species (ROS) and oxidative stress are thought to play a central role in potentiating macrophage activation, causing excessive inflammation, tissue damage, and sepsis. Recently, we have shown that punicalagin (PUN) exhibits anti-inflammatory activity in LPS-stimulated macrophages. However, the potential antioxidant effects of PUN in macrophages remain unclear. Revealing these effects will help understand the mechanism underlying its ability to inhibit excessive macrophage activation. Hemeoxygenase-1 (HO-1) exhibits antioxidant activity in macrophages. Therefore, we hypothesized that HO-1 is a potential target of PUN and tried to reveal its antioxidant mechanism. Here, PUN treatment increased HO-1 expression together with its upstream mediator nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). However, specific inhibition of Nrf2 by brusatol (a specific Nrf2 inhibitor) dramatically blocked PUN-induced HO-1 expression. Previous research has demonstrated that the PI3K/Akt pathway plays a critical role in modulating Nrf2/HO-1 protein expression as an upstream signaling molecule. Here, LY294002, a specific PI3K/Akt inhibitor, suppressed PUN-induced HO-1 expression and led to ROS accumulation in macrophages. Furthermore, PUN inhibited LPS-induced oxidative stress in macrophages by reducing ROS and NO generation and increasing superoxide dismutase (SOD) 1 mRNA expression. These findings provide new perspectives for novel therapeutic approaches using antioxidant medicines and compounds against oxidative stress and excessive inflammatory diseases including tissue damage, sepsis, and endotoxemic shock.

Indexed as

Cell LineHeme Oxygenase-1HumansHydrolyzable TanninsMacrophagesNF-E2-Related Factor 2Oxidative StressPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktHeme Oxygenase-1Hydrolyzable TanninsNFE2L2 protein, humanNF-E2-Related Factor 2Phosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktpunicalagin

Identifiers

PMID25969626
PMCPMC4417599
OpenAlexW1981636754

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.