ArticlePloS one
Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages.
Article in PloS one. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- Agmatine Sulfate Is Associated with Altered Redox Status, Apoptosis-Associated Responses, and AKT/JNK Signalling in Ishikawa Endometrial Cancer Cells.Life (Basel, Switzerland) · 2026Article
- Agmatine induces mitophagy via the PTS-I2R pathway to increase autophagic flux and attenuate sepsis-induced intestinal epithelial cell apoptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Evaluation of agmatine's anti-cancer efficacy in Caco-2 colorectal adenocarcinoma cells.Medical oncology (Northwood, London, England) · 2026Article
- Agmatine Abrogates Tacrolimus-Induced Testicular Injury in Rats.Pharmaceutics · 2025Article
- The roles of arginases and arginine in immunity.Nature reviews. Immunology · 2025Review
- Therapeutic Potential of Agmatine in Essential Tremor Through Regulation of Lingo-1 and Inflammatory Pathways.Brain and behavior · 2025Article
- Agmatine-IRF2BP2 interaction induces M2 phenotype of microglia by increasing IRF2-KLF4 signaling.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- miR‑151a‑5p promotes the proliferation and metastasis of colorectal carcinoma cells by targeting AGMAT.Oncology reports · 2023Article
- New Insights into the Gut Microbiota in Neurodegenerative Diseases from the Perspective of Redox Homeostasis.Antioxidants (Basel, Switzerland) · 2022Review
- Delineating transcriptional crosstalk between Mycobacterium avium subsp. paratuberculosis and human THP-1 cells at the early stage of infection via dual RNA-seq analysis.Veterinary research · 2022Article
- Interplay of gut microbiota and oxidative stress: Perspective on neurodegeneration and neuroprotection.Journal of advanced research · 2022Review
- Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response.International journal of molecular sciences · 2022Article
- A Dual Role of Heme Oxygenase-1 in Tuberculosis.Frontiers in immunology · 2022Review
- Fucoxanthin inhibits lipopolysaccharide-induced inflammation and oxidative stress by activating nuclear factor E2-related factor 2 via the phosphatidylinositol 3-kinase/AKT pathway in macrophages.European journal of nutrition · 2021Article
- Maintenance of the Neuroprotective Function of the Amino Group Blocked Fluorescence-Agmatine.Neurochemical research · 2021Article
- Arginine-dependent immune responses.Cellular and molecular life sciences : CMLS · 2021Review
- Nitric Oxide Modulates Metabolic Processes in the Tumor Immune Microenvironment.International journal of molecular sciences · 2021Review
- Exploring the Protective Effects and Mechanism of Crocetin From Saffron Against NAFLD by Network Pharmacology and Experimental Validation.Frontiers in medicine · 2021Article
- The protective effect of glycyrrhizin on hepatic ischemia-reperfusion injury in rats and possible related signal pathway.Iranian journal of basic medical sciences · 2020Article
- CD28 Deficiency Ameliorates Thoracic Blast Exposure-Induced Oxidative Stress and Apoptosis in the Brain through the PI3K/Nrf2/Keap1 Signaling Pathway.Oxidative medicine and cellular longevity · 2019Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages are key responders of inflammation and are closely related with oxidative stress. Activated macrophages can enhance oxygen depletion, which causes an overproduction of reactive oxygen species (ROS) and leads to further excessive inflammatory response and tissue damage. Agmatine, an endogenous metabolite of L-arginine, has recently been shown to have neuroprotective effects based on its antioxidant properties. However, the antioxidant effects of agmatine in peripheral tissues and cells, especially macrophages, remain unclear. In this study we explored the role of agmatine in mediating antioxidant effects in RAW 264.7 cells and studied its antioxidant mechanism. Our data demonstrate that agmatine is an activator of Nrf2 signaling that markedly enhances Nrf2 nuclear translocation, increases nuclear Nrf2 protein level, up-regulates the expression of the Nrf2 downstream effector HO-1, and attenuates ROS generation induced by Lipopolysaccharide (LPS). We further demonstrated that the agmatine-induced activation of Nrf2 is likely through the PI3K/Akt pathway. LY294002, a specific PI3K/Akt inhibitor, abolished agmatine-induced HO-1 up-regulation and ROS suppression significantly. Inhibiting HO-1 pathway significantly attenuated the antioxidant effect of agmatine which the products of HO-1 enzymatic activity contributed to. Furthermore, the common membrane receptors of agmatine were evaluated, revealing that α2-adrenoceptor, I1-imidazoline receptor or I2-imidazoline receptor are not required by the antioxidant properties of agmatine. Taken together, our findings revealed that agmatine has antioxidant activity against LPS-induced ROS accumulation in RAW 264.7 cells involving HO-1 expression induced by Nrf2 via PI3K/Akt pathway activation.
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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.