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Cited by 4Liver physiology and pathologyDrug-Induced Hepatotoxicity and ProtectionImmune Response and Inflammation

Alpha Ketoglutaric Acid attenuates LPS Induced Inflammatory Response by Inhibiting the PKCε/MAPK/P65 Signaling Pathway and Inhibit Oxidative Stress in Kupffer Cells

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Li, Yanfei, Kuang, Haoran, Fan, Guoqiang, Yang, Xiaojing·2025·Inflammation
DOI 10.1007/s10753-025-02308-2PMC PMC12722334
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Abstract

The inflammatory response is crucial in the progression of various liver diseases. Many diseases are linked with inflammation, such as ischemia and reperfusion injury, nonalcoholic steatohepatitis (NASH) and hepatic fibrosis. Research indicates that αKG attenuates NASH. However, the protective effect of αKG on KCs cell inflammation and its mechanism remain unclear. This study aimed to explore the role and mechanism of αKG in LPS-induced inflammation. The inflammatory damage model of KCs was induced by LPS. The study found that αKG supplementation significantly decreased inflammatory and antioxidant indexes in the LPS group, with a notable reduction in LPS-induced inflammation-related factors (P < 0.05). iNOS and COX2 are also used as indicators of macrophage inflammation, and αKG significantly alleviates LPS induced iNOS and COX2 levels (P < 0.05). Further detection of mitochondrial function and oxidative stress indexes showed that αKG supplementation significantly restored mitochondrial damage caused by LPS, inhibited ROS production, restored mitochondrial function, and improved cellular antioxidant capacity (P < 0.05). Finally, it was found that LPS treatment significantly promoted the activation of PKCε/MAPK/P65 signaling pathway, and αKG supplementation significantly inhibited the activation of signaling pathway and alleviated the pro-inflammatory effect of LPS (P < 0.05). The study demonstrated that αKG enhances the anti-inflammatory effects of KCs by decreasing ROS production and inhibiting the PKCε/MAPK/P65 signaling pathway. This is helpful for development the αKG related anti-inflammation drugs to relieving the liver inflammatory response.

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  • Improved mitochondrial function, including enhanced oxidative phosphorylation and mitochondrial biogenesis, is consistently associated with macrophage reprogramming and fibrosis resolution.

    “Conversely, improved mitochondrial function -including enhanced oxidative phosphorylation and mitochondrial biogenesis- has been consistently associated with macrophage reprogramming and fibrosis resolution (28–31).”

    From Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages (2026) · cites this paper as [31]

    The Results section ('αKG Restores LPS-Induced Mitochondrial Function Dysfunction in Kupffer Cells'; page not provided) reports improved mitochondrial markers after αKG treatment, and the Introduction links metabolic reprogramming with macrophage polarization. The paper does not report enhanced oxidative phosphorylation or mitochondrial biogenesis, or show that these changes are associated with fibrosis resolution. (LLM, conf=0.87)

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Sorted by citations

Authors
Li, Y., Kuang, H., Fan, G., & Yang, X.
Affiliations
Nanjing Agricultural University (CN)
Corresponding author
Yang, Xiaojing
ORCID
Venue
Inflammation
Publisher
Springer Science and Business Media LLC
Published
2025-06-27
Volume
48
Issue
6
Pages
4020-4030
ISSN
  • 0360-3997 (ISSN-L)
  • 1573-2576
DOI
10.1007/s10753-025-02308-2
PMC
PMC12722334
OpenAlex
W4411680746
Cited by
4
References
3
Citations by year
2026: 3 · 2025: 1
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Inflammation (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
Funders
  • National Key Research and Development Program of China (2024YFD2000302)
  • National Natural Science Foundation of China (32472991)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
alpha-ketoglutarate, Kupffer cells, lipopolysaccharide-induced inflammation, oxidative stress, reactive oxygen species, mitochondrial dysfunction, inducible nitric oxide synthase, cyclooxygenase-2, liver inflammation, nonalcoholic steatohepatitis, anti-inflammatory agents
MeSH terms
Animals, Inflammation, Kupffer Cells, Lipopolysaccharides, Signal Transduction, Oxidative Stress, MAP Kinase Signaling System, Mice, Transcription Factor RelA

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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