ArticleBritish journal of pharmacology2018
Shikonin inhibits myeloid differentiation protein 2 to prevent LPS-induced acute lung injury.
Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 71 citations in OpenAlex.
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- OTUD6A in Airway Epithelial Cells Exacerbates Allergic Asthma by Promoting Airway Inflammation and Airway Remodeling Through Deubiquitination of hResistin/mRELMα.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ganoderic Acids Alleviate Neuroinflammation by Targeting Myeloid Differentiation Factor 2 for Ischemic Stroke Therapy.Exploration (Beijing, China) · 2026Article
- Targeting myeloid differentiation protein 2 ameliorates rheumatoid arthritis by inhibiting inflammation and ferroptosis via MAPK and NF-κB signaling pathways.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Myeloid MyD88 Mediates Macrophage Infiltration and Activation in Ang II-Induced Cardiac Hypertrophy.Journal of cellular and molecular medicine · 2025Article
- Identification of Rhododendron mariae extraction as a new attachment inhibitor against dengue virus by targeting the envelope protein domain III.Frontiers in immunology · 2025Article
- Review
- Chalcone-derivative L6H21 attenuates the OVA-induced asthma by targeting MD2.European journal of medical research · 2024Article
- Curcumin attenuates memory impairments and long-term potentiation deficits by damping hippocampal inflammatory cytokines in lipopolysaccharide-challenged rats.Metabolic brain disease · 2023Article
- Immunohistochemical Localization of MD2, a Co-Receptor of TLR4, in the Adult Mouse Brain.ACS chemical neuroscience · 2023Article
- Article
- Can natural products modulate cytokine storm in SARS-CoV2 patients?Biotechnology reports (Amsterdam, Netherlands) · 2022Review
- Restorative effects of Rg3-enriched Korean Red Ginseng andJournal of ginseng research · 2022Article
- FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NFκB pathway.Cell death & disease · 2022Article
- Synergistic Antibacterial Activity with Conventional Antibiotics and Mechanism of Action of Shikonin against Methicillin-ResistantInternational journal of molecular sciences · 2022Article
- Myeloid-Specific Pyruvate-Kinase-Type-M2-Deficient Mice Are Resistant to Acute Lung Injury.Biomedicines · 2022Article
- VIP alleviates sepsis-induced cognitive dysfunction as the TLR-4/NF-κB signaling pathway is inhibited in the hippocampus of rats.Journal of molecular histology · 2022Article
- Cellular Imaging Analysis Algorithm-Based Assessment and Prediction of Disease in Patients with Acute Lung Injury.Contrast media & molecular imaging · 2022Article
- Selenium-Containing Compound Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Regulating the MAPK/AP-1 Pathway.Inflammation · 2021Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeAcute lung injury (ALI) is a challenging clinical syndrome, which manifests as an acute inflammatory response. Myeloid differentiation protein 2 (MD2) has an important role in mediating LPS-induced inflammation. Currently, there are no effective molecular-based therapies for ALI or viable biomarkers for predicting the severity of disease. Recent preclinical studies have shown that shikonin, a natural naphthoquinone, prevents LPS-induced inflammation. However, little is known about the underlying mechanisms. EXPERIMENTAL APPROACH: The binding affinity of shikonin to MD2 was analysed using computer docking, surface plasmon resonance analysis and elisa. In vitro, the anti-inflammatory effect and mechanism of shikonin were investigated through elisa, real-time quantitative reverse transcription PCR, Western blotting and immunoprecipitation assay. In vivo, lung injury was induced by intratracheal administration of LPS and assessed by changes in the histopathological and inflammatory markers. The underlying mechanisms were investigated by immunoprecipitation in lung tissue. KEY
resultsShikonin directly bound to MD2 and interfered with the activation of toll-like receptor 4 (TLR4) induced by LPS. In cultured macrophages, shikonin inhibited TLR4 signalling and pro-inflammatory cytokine production. These effects were produced through suppression of key signalling proteins including the NF-κB and the MAPK pathway. We also showed that shikonin inhibits MD2-TLR4 complex formation and reduces LPS-induced inflammatory responses in a mouse model of ALI. CONCLUSIONS AND IMPLICATIONS: Our studies have uncovered the mechanism underlying the biological activity of shikonin in ALI and suggest that the targeting of MD2 may prove to be beneficial as a treatment option for this condition.
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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 OpenQuestion graph.