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2′-Hydroxycinnamaldehyde mitigates acetaminophen-induced acute liver injury by inhibiting the Warburg effect-mediated pyroptosis via the PKM2-NLRP3 axis
- Source :
- Journal of Functional Foods, Vol 110, Iss , Pp 105872- (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver injury. However, the underlying mechanisms appear to be multifaceted and there are few effective treatments. In this study, we used the 2′-Hydroxycinnamaldehyde (HCA), an active ingredient extracted from cinnamon stem bark to evaluate the therapeutic effect against APAP-induced ALI. The results indicated that pyruvate kinase M2 (PKM2)-mediated aerobic glycolysis may activate NLRP3 inflammasome in APAP-induced ALI, However, this process was prevented by HCA. Additionally, overexpression of PKM2 by adeno-associated virus (AAV9-PKM2) in vivo and plasmid (PKM2-OE) in vitro reversed the inhibition of NLRP3 inflammasome by HCA. Intriguingly, the HCA-triggered repressive pyroptosis was mediated through dephosphorylation and nuclear translocation of PKM2. Furthermore, the therapeutic effect of HCA on APAP-induced ALI was achieved by partially stimulating the Akt-mTOR signaling pathway, thus inhibiting the PKM2-NLRP3 axis. These findings elucidate that a potential drug to the clinical treatment of APAP overdose by HCA.
Details
- Language :
- English
- ISSN :
- 17564646
- Volume :
- 110
- Issue :
- 105872-
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Functional Foods
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.69a974e1564d5e83a1c2d00d3b8e9c
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.jff.2023.105872