ArticleActa pharmacologica Sinica2018
Ulinastatin attenuates LPS-induced inflammation in mouse macrophage RAW264.7 cells by inhibiting the JNK/NF-κB signaling pathway and activating the PI3K/Akt/Nrf2 pathway.
Article in Acta pharmacologica Sinica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 5 of them syntheses that pooled it.
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Who cites it
116 citing papers in PubMed, 5 syntheses or guidelines pooled it, 195 citations in OpenAlex.
- Comparative efficacy and safety of immunomodulatory therapies for sepsis: a systematic review and network meta-analysis.Frontiers in medicine · 2026Pooled it
- MiRNA-loaded MSC exosomes restore autophagy flux for acute pancreatitis therapy.Frontiers in immunology · 2025Pooled it
- Effects of anesthetic adjunctive agents on postoperative cognitive dysfunction in elderly patients undergoing noncardiac surgery: A Bayesian network meta-analysis.Brain and behavior · 2023Pooled it
- The effect of Ulinastatin on postoperative course in cardiopulmonary bypass patients in Asia: a meta-analysis of randomized controlled trials.Journal of cardiothoracic surgery · 2022Pooled it
- Effect of Ulinastatin on Early Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Surgery: A Systemic Review and Meta-Analysis.Frontiers in neuroscience · 2021Pooled it
- Non-reproductive tumor progression impairs ovarian function through CXCL10-IL18R1 axis.Experimental & molecular medicine · 2026Article
- Ulinastatin Treatment Associated with Lower Sepsis-Associated Encephalopathy Risk in Sepsis Patients: A Multicenter Observational Study.Shock (Augusta, Ga.) · 2026Observational
- Integrative multi-omics analysis identifies C-type lectin CNVs as functional targets for breeding mastitis-resistant dairy goats.Animal microbiome · 2026Article
- Dose-Dependent Efficacy of Ulinastatin in Improving 28-Day and 30-Day Survival Rates in Sepsis: A Systematic Review and Meta-Analysis.Journal of clinical medicine · 2026Review
- Unraveling the Link Between Azathioprine and Acute Pancreatitis: Integrating Network Toxicology, Machine Learning, and Mendelian Randomization.CPT: pharmacometrics & systems pharmacology · 2026Article
- Acute pancreatitis: mechanisms and therapeutic approaches.Signal transduction and targeted therapy · 2026Review
- Transducin-like enhancer of split 3 protects against lipopolysaccharide-induced inflammation through DEAD-box helicase 5-activating transcription factor 1-protein phosphatase 2 regulatory subunit 5A signaling.Journal of advanced research · 2026Article
- Zinc Deficiency Aggravates High-Fat Diet-Induced Renal Injury by Regulating Oxidative Stress and Inflammation via the Nrf2/HO-1 Pathway.Biological trace element research · 2026Article
- Adsorption-mediated modulation of lipopolysaccharide bioactivity by clinoptilolite zeolite withFrontiers in immunology · 2026Article
- Orthosilicic Acid Promotes Diabetic Wound Healing Through the PI3 K/AKT/mTOR Signaling Pathway.Biological trace element research · 2026Article
- Assessing the mechanism of osteosarcoma induced by long-term PET exposure: prediction from combined network toxicology, machine learning and molecular docking.Journal of bone oncology · 2025Article
- Alpha Ketoglutaric Acid attenuates LPS Induced Inflammatory Response by Inhibiting the PKCε/MAPK/P65 Signaling Pathway and Inhibit Oxidative Stress in Kupffer Cells.Inflammation · 2025Article
- Article
- Biochanin A prevents neurodegeneration and oxidative stress in a kainic acid model of epilepsy by activating the PI3K/Akt/Nrf2 signaling pathway.Scientific reports · 2025Article
- Review
56 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor isolated and purified from human urine with strong anti-inflammatory and cytoprotective actions, which is widely used for the treatment of various diseases, such as pancreatitis and sepsis. Although the therapeutic effects of UTI are reported to be associated with a variety of mechanisms, the signaling pathways mediating the anti-inflammatory action of UTI remain to be elucidated. In the present study we carried out a systematic study on the anti-inflammatory and anti-oxidative mechanisms of UTI and their relationships in LPS-treated RAW264.7 cells. Pretreatment with UTI (1000 and 5000 U/mL) dose-dependently decreased the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, iNOS) and upregulated anti-inflammatory cytokines (IL-10 and TGF-β1) in LPS-treated RAW264.7 cells. UTI pretreatment significantly inhibited the nuclear translocation of NF-κB by preventing the degradation of IκB-α. UTI pretreatment only markedly inhibited the phosphorylation of JNK at Thr183, but it did not affect the phosphorylation of JNK at Tyr185, ERK-1/2 and p38 MAPK; JNK was found to function upstream of the IκB-α/NF-κB signaling pathway. Furthermore, UTI pretreatment significantly suppressed LPS-induced ROS production by activating PI3K/Akt pathways and the nuclear translocation of Nrf2 via promotion of p62-associated Keap1 degradation. However, JNK was not involved in mediating the anti-oxidative stress effects of UTI. In summary, this study shows that UTI exerts both anti-inflammatory and anti-oxidative effects by targeting the JNK/NF-κB and PI3K/Akt/Nrf2 pathways.
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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 Socratic graph.