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Dual anti-inflammatory effects of curcumin and berberine on acetaminophen-induced liver injury in mice by inhibiting NF-κB activation via PI3K/AKT and PPARγ signaling pathways.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 19; Vol. 734, pp. 150772. Date of Electronic Publication: 2024 Sep 30. - Publication Year :
- 2024
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Abstract
- Acetaminophen (APAP) overdose is still a leading cause of drug-induced liver injury (DILI), accompanied with severe inflammatory response. However, the therapy for APAP-induced DILI is rather limited. The combined application of natural products to treat DILI induced by APAP may be a new direction of the research. This study was conducted to evaluate the dual anti-inflammatory activity of curcumin (CUR) combined with berberine (BBR) against APAP-mediated DILI. Network pharmacology found that PI3K-Akt and PPAR signaling pathways were primarily involved in anti-DILI of the combination of CUR and BBR. APAP injection enhanced the levels of ALT, AST, IL-1β, IL-6, and TNF-α in mice, while such phenomenon was significantly reversed by the cotreatment of CUR and BBR, which was more effective than either single treatment. The increase of p-NF-κB and p-IKKα/β protein expression and the decrease of p-PI3K, p-AKT, and PPARγ protein expression in APAP-treated mice were markedly inhibited by the coadministration of CUR and BBR. Molecular docking further demonstrated that both CUR and BBR could stably bind to PI3K, AKT, and PPARγ protein. In conclusion, the combination of CUR and BBR more effectively protected liver from APAP-triggered DILI than individual treatment. The mechanism is to alleviate hepatic inflammation by inhibiting NF-κB activation, which is possibly mediated by PI3K/Akt and PPARγ signaling pathways.<br />Competing Interests: Declaration of competing interest The authors declare no competing financial interests.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Male
Molecular Docking Simulation
Liver drug effects
Liver metabolism
Liver pathology
Berberine pharmacology
Berberine therapeutic use
PPAR gamma metabolism
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction drug effects
Curcumin pharmacology
Curcumin therapeutic use
Chemical and Drug Induced Liver Injury metabolism
Chemical and Drug Induced Liver Injury drug therapy
Chemical and Drug Induced Liver Injury prevention & control
Chemical and Drug Induced Liver Injury pathology
NF-kappa B metabolism
Phosphatidylinositol 3-Kinases metabolism
Acetaminophen adverse effects
Acetaminophen toxicity
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 734
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 39362031
- Full Text :
- https://doi.org/10.1016/j.bbrc.2024.150772