ArticleLaboratory investigation; a journal of technical methods and pathology2017
Roflumilast reverses polymicrobial sepsis-induced liver damage by inhibiting inflammation in mice.
Article in Laboratory investigation; a journal of technical methods and pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Contribution of p38 MAPK in liver fibrosis: An overview of mechanisms, signaling pathways, and therapeutic targets (Review).International journal of molecular medicine · 2026Review
- Phosphodiesterase 4 Inhibitor Roflumilast Ameliorates Polytrauma-Induced Acute Kidney Injury by Attenuating HMGB1 and Renal Inflammatory Pathways in Rats.International journal of molecular sciences · 2026Article
- The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.Biomarker research · 2026Review
- Targeting Phosphodiesterase 4 in Gastrointestinal and Liver Diseases: From Isoform-Specific Mechanisms to Precision Therapeutics.Biomedicines · 2025Review
- Shenfu injection alleviates lipopolysaccharide-induced liver injury in septic mice.Scientific reports · 2025Article
- Selective phosphodiesterase 4 inhibitor roflumilast reduces inflammation and lung injury in models of betacoronavirus infection in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- The Protective Effect of Roflumilast Against Acute Hepatotoxicity Caused by Methotrexate in Wistar Rats: In vivo Evaluation.Drug design, development and therapy · 2024Article
- Potential application of ginseng in sepsis:: Applications of ginseng in sepsis.Journal of ginseng research · 2023Review
- Phosphodiesterase-4 Inhibitor Roflumilast-Mediated Protective Effect in Sepsis-Induced Late-Phase Event of Acute Kidney Injury: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Novel Liposomal Rolipram Formulation for Clinical Application to Reduce Emesis.Drug design, development and therapy · 2022Article
- Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis.Experimental and therapeutic medicine · 2021Article
- Knockdown of lncRNA LUCAT1 attenuates sepsis‑induced myocardial cell injury by sponging miR-642a.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Article
- Structure-Based Identification of Potential Drugs Against FmtA of Staphylococcus aureus: Virtual Screening, Molecular Dynamics, MM-GBSA, and QM/MM.The protein journal · 2021Article
- Neuroprotective effects of roflumilast against quinolinic acid-induced rat model of Huntington's disease through inhibition of NF-κB mediated neuroinflammatory markers and activation of cAMP/CREB/BDNF signaling pathway.Inflammopharmacology · 2021Article
- Scope of adjuvant therapy using roflumilast, a PDE-4 inhibitor against COVID-19.Pulmonary pharmacology & therapeutics · 2021Review
- Samotolisib Attenuates Acute Liver Injury Through Inhibiting Caspase-11-Mediated Pyroptosis Via Regulating E3 Ubiquitin Ligase Nedd4.Frontiers in pharmacology · 2021Article
- New putative insights into neprilysin (NEP)-dependent pharmacotherapeutic role of roflumilast in treating COVID-19.European journal of pharmacology · 2020Review
- Roflumilast, a Phosphodiesterases-4 (PDE4) Inhibitor, Alleviates Sepsis‑induced Acute Kidney Injury.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Acetic acid alleviates the inflammatory response and liver injury in septic mice by increasing the expression of TRIM40.Experimental and therapeutic medicine · 2019Article
- Role of cAMP and phosphodiesterase signaling in liver health and disease.Cellular signalling · 2018Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis is a life-threatening syndrome accompanied by an overwhelming inflammatory response and organ dysfunction. Selective targeting of phosphodiesterase 4 (PDE4) is currently being investigated as an effective therapeutic approach for inflammation-associated diseases. Roflumilast is a selective PDE4 inhibitor, used for the treatment of severe chronic obstructive pulmonary disease in clinic. However, its role in the treatment of sepsis-induced liver damage remains unclear. In the present study, we evaluated the effects of roflumilast in mice with cecal ligation and puncture-induced sepsis, and investigated the underlying mechanism. We found that roflumilast treatment improved survival in septic mice by reducing bacterial load locally and systemically, inhibiting the expression of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor alpha, and alleviating liver injury. These effects were associated with the inhibition of nuclear translocation of nuclear factor-kappa B (NF-κB), as well as degradation of NF-κB inhibitory protein alpha. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was also markedly inhibited by roflumilast. Moreover, roflumilast significantly suppressed the activation of signal transducer and activator of transcription 3 (STAT3) and its upstream Janus kinase 1 and Janus kinase 2. Taken together, these results indicate that roflumilast prevents polymicrobial sepsis likely by suppressing NF-κB, p38 MAPK, and STAT3 pathways.
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