ArticleMolecular medicine (Cambridge, Mass.)2016
Plumbagin Protects Mice from Lethal Sepsis by Modulating Immunometabolism Upstream of PKM2.
Article in Molecular medicine (Cambridge, Mass.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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.
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.
Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- PKM2: A gatekeeper in macrophage metabolic reprogramming.Journal of pharmaceutical analysis · 2026Review
- Macrophage metabolism reprogramming in sepsis: Pathogenesis and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- Immunometabolic reprogramming in sepsis: mechanisms, clinical endotypes, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Correction: Plumbagin protects mice from lethal Sepsis by modulating immunometabolism upstream of PKM2.Molecular medicine (Cambridge, Mass.) · 2025Article
- Unveiling the power of plumbagin: revitalizing exhausted T cells to combat tongue cancer.Cancer cell international · 2025Article
- PKM2-mediated metabolic reprogramming of microglia in neuroinflammation.Cell death discovery · 2025Review
- Extracellular NCOA4 is a mediator of septic death by activating the AGER-NFKB pathway.Autophagy · 2024Article
- [Plumbagin protect against sepsis-induced myocardial injury in mice by inhibiting the JAK2/STAT3 signaling pathway to reduce cardiomyocyte pyroptosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Plumbagin inhibits fungal growth, HMGB1/LOX-1 pathway and inflammatory factors inFrontiers in microbiology · 2024Article
- KITENIN promotes aerobic glycolysis through PKM2 induction by upregulating the c-Myc/hnRNPs axis in colorectal cancer.Cell & bioscience · 2023Article
- Plumbagin, a Natural Compound with Several Biological Effects and Anti-Inflammatory Properties.Life (Basel, Switzerland) · 2023Review
- Monitoring Mitochondria Function in Ferroptosis.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Plumbagin rescues the granulosa cell's pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndrome.Journal of ovarian research · 2022Article
- Podocyte specific deletion of PKM2 ameliorates LPS-induced podocyte injury through beta-catenin.Cell communication and signaling : CCS · 2022Article
- Plumbagin relieves rheumatoid arthritis through nuclear factor kappa-B (NF-κB) pathway.Bioengineered · 2022Article
- Standardized fraction of Xylocarpus moluccensis inhibits inflammation by modulating MAPK-NFκB and ROS-HIF1α-PKM2 activation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Sepsis-induced myocardial dysfunction: the role of mitochondrial dysfunction.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Review
- Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties.International journal of molecular sciences · 2021Article
- FAM96A knock-out promotes alternative macrophage polarization and protects mice against sepsis.Clinical and experimental immunology · 2021Article
- Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm.Frontiers in immunology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
Sepsis is characterized by dysregulated systemic inflammation with release of early (for example, interleukin (IL)-1β) and late (for example, HMGB1) proinflammatory mediators from macrophages. Plumbagin, a medicinal plant-derived naphthoquinone, has been reported to exhibit antiinflammatory activity, but the underling mechanisms remain unclear. Here, we have demonstrated that plumbagin inhibits the inflammatory response through interfering with the immunometabolism pathway in activated macrophages. Remarkably, plumbagin inhibited lipopolysaccharide (LPS)-induced aerobic glycolysis by downregulating the expression of pyruvate kinase M2 (PKM2), a protein kinase responsible for the final and rate-limiting reaction step of the glycolytic pathway. Moreover, the NADPH oxidase 4 (NOX4)-mediated oxidative stress was required for LPS-induced PKM2 expression, because pharmacologic or genetic inhibition of NOX4 by plumbagin or RNA interference limited LPS-induced PKM2 expression, lactate production and subsequent proinflammatory cytokine (IL-1β and HMGB1) release in macrophages. Finally, plumbagin protected mice from lethal endotoxemia and polymicrobial sepsis induced by cecal ligation and puncture. These findings identify a new approach for inhibiting the NOX4/PKM2-dependent immunometabolism pathway in the treatment of sepsis and inflammatory diseases.
Identifiers
What OpenQuestion holds
Registered trials
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.