Quercetin protects against LPS-induced lung injury in mice via SIRT1-mediated suppression of PKM2 nuclear accumulation
European Journal of Pharmacology, ISSN: 0014-2999, Vol: 936, Page: 175352
2022
- 36Citations
- 17Captures
- 1Mentions
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Metrics Details
- Citations36
- Citation Indexes36
- 36
- CrossRef16
- Captures17
- Readers17
- 17
- Mentions1
- News Mentions1
- News1
Most Recent News
Quercetin is a Potential Therapy for Rheumatoid Arthritis via Targeting Caspase-8 Through Ferroptosis and Pyroptosis
Introduction Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by persistent synovitis and can destroy bone and cartilage tissue, leading to joint damage, chronic
Article Description
The role of NOD-like receptor protein 3 (NLRP3)-mediated macrophages pyroptosis in acute lung injury (ALI) is well-established. Quercetin (Que) is a natural bioflavonoid compound with anti-inflammatory and antioxidative properties that reportedly inhibits the NLRP3 inflammasome in sepsis-induced organ dysfunctions such as ALI. However, the mechanism underlying the inhibitory effect of quercetin on NLRP3 activation remains unclear. In this study, we established an endotoxin-induced ALI mouse model with an in vitro LPS challenge. We demonstrated that the administration of quercetin could significantly reduce pulmonary injury and decrease the production of pro-inflammatory cytokines. Moreover, we found that quercetin could inhibit the activation of the NLRP3 inflammasome by suppressing the nuclear accumulation of PKM2 and increasing SIRT1 levels. Importantly, treatment with SRT1720 (a specific SIRT1 activator) could inhibit the nuclear accumulation of PKM2 and the activation of NLRP3. Besides, preventing PKM2 dimerization with ML265 yielded an anti-inflammatory effect, similar to findings observed for SRT1720. In addition, we found that SIRT1 silencing or inhibition by EX527 could increase NLRP3 activation and nuclear accumulation of PKM2 and override quercetin-mediated anti-inflammatory activity. These findings indicated that quercetin could downregulate NLRP3 inflammasome activation by inhibiting the nuclear accumulation of PKM2 and upregulating SIRT1 expression, expanding the treatment landscape for ARDS.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0014299922006136; http://dx.doi.org/10.1016/j.ejphar.2022.175352; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85140994873&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/36309049; https://linkinghub.elsevier.com/retrieve/pii/S0014299922006136; https://dx.doi.org/10.1016/j.ejphar.2022.175352
Elsevier BV
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