ArticleScientific reports2016
The citrus flavonoid naringenin confers protection in a murine endotoxaemia model through AMPK-ATF3-dependent negative regulation of the TLR4 signalling pathway.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Pooled it
- Modulation of Cognitive Function by TRPM3 Channels in the Dentate Gyrus of a Menopausal Rat Model: Effects of Naringenin Treatment and Ciliary Neurotrophic Factor.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- LC-MS-based metabolomic characterization ofRSC advances · 2025Article
- Metabolic Reprogramming Through Polyphenol Networks: A Systems Approach to Metabolic Inflammation and Insulin Resistance.Medical sciences (Basel, Switzerland) · 2025Review
- An Updated Review of the Anticancer Mechanisms and Therapeutic Potential of Naringenin.Food science & nutrition · 2025Review
- Flavanones as Modulators of Gut Microbiota and Cognitive Function.Molecules (Basel, Switzerland) · 2025Review
- Neutrophil heterogeneity and plasticity: unveiling the multifaceted roles in health and disease.MedComm · 2025Review
- COVID-19-Associated Sepsis: Potential Role of Phytochemicals as Functional Foods and Nutraceuticals.International journal of molecular sciences · 2024Review
- Acute exposure to polystyrene nanoparticles promotes liver injury by inducing mitochondrial ROS-dependent necroptosis and augmenting macrophage-hepatocyte crosstalk.Particle and fibre toxicology · 2024Article
- Oxidative stress signaling in the pathogenesis of diabetic cardiomyopathy and the potential therapeutic role of antioxidant naringenin.Redox report : communications in free radical research · 2023Review
- Glycerol monolaurate improves intestinal morphology and antioxidant status by suppressing inflammatory responses and nuclear factor kappa-B signaling in lipopolysaccharide-exposed chicken embryos.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2023Article
- Activating transcription factor 3: A potential therapeutic target for inflammatory pulmonary diseases.Immunity, inflammation and disease · 2023Review
- Antioxidant Compounds and Health Benefits of Citrus Fruits.Antioxidants (Basel, Switzerland) · 2023Article
- Inhibition of TLR4 Alleviates Heat Stroke-Induced Cardiomyocyte Injury by Down-Regulating Inflammation and Ferroptosis.Molecules (Basel, Switzerland) · 2023Article
- The pathogenesis and therapeutic strategies of heat stroke-induced myocardial injury.Frontiers in pharmacology · 2023Review
- Naringenin and Its Derivatives-Health-Promoting Phytobiotic against Resistant Bacteria and Fungi in Humans.Antibiotics (Basel, Switzerland) · 2022Review
- Modulation of the tumor microenvironment by natural agents: implications for cancer prevention and therapy.Seminars in cancer biology · 2022Review
- Acute exposure to gold nanoparticles aggravates lipopolysaccharide-induced liver injury by amplifying apoptosis via ROS-mediated macrophage-hepatocyte crosstalk.Journal of nanobiotechnology · 2022Article
- Naringenin is a Potential Anabolic Treatment for Bone Loss by Modulating Osteogenesis, Osteoclastogenesis, and Macrophage Polarization.Frontiers in pharmacology · 2022Article
- Beneficial effects of naringenin and morin on interleukin-5 and reactive oxygen species production in BALB/c mice with ovalbumin-induced asthma.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive activation of the TLR4 signalling pathway is critical for inflammation-associated disorders, while negative regulators play key roles in restraining TLR4 from over-activation. Naringenin is a citrus flavonoid with remarkable anti-inflammatory activity, but the mechanisms underlying its inhibition of LPS/TLR4 signalling are less clear. This study investigated the molecular targets and therapeutic effects of naringenin in vitro and in vivo. In LPS-stimulated murine macrophages, naringenin suppressed the expression of TNF-α, IL-6, TLR4, inducible NO synthase (iNOS), cyclo-oxygenase-2 (COX2) and NADPH oxidase-2 (NOX2). Naringenin also inhibited NF-κB and mitogen-activated protein kinase (MAPK) activation. However, it did not affect the IRF3 signalling pathway or interferon production, which upregulate activating transcription factor 3 (ATF3), an inducible negative regulator of TLR4 signalling. Naringenin was demonstrated to directly increase ATF3 expression. Inhibition of AMPK and its upstream calcium-dependent signalling reduced ATF3 expression and dampened the anti-inflammatory activity of naringenin. In murine endotoxaemia models, naringenin ameliorated pro-inflammatory reactions and improved survival. Furthermore, it induced AMPK activation in lung tissues, which was required for ATF3 upregulation and the enhanced anti-inflammatory activity. Overall, this study reveals a novel mechanism of naringenin through AMPK-ATF3-dependent negative regulation of the LPS/TLR4 signalling pathway, which thereby confers protection against murine endotoxaemia.
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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.