Quercetin inhibits mitophagy-mediated apoptosis and inflammatory response by targeting the PPARγ/PGC-1α/NF-κB axis to improve acute liver failure
Abstract
BACKGROUND: Reactive oxygen species (ROS) from mitochondrial dysfunction are critical in triggering apoptosis and inflammation in acute liver failure (ALF). Quercetin (QUE), an antioxidant, is renowned for its therapeutic effects onliverdiseases. There are no studies on whether QUE regulates mitophagy level in hepatocytes to inhibit ALF.
OBJECTIVE: This study investigates QUE's protective effects on ALF and elucidates the mechanisms involved.
METHODS: The ALF and hepatocyte inflammatory injury model was established using LPS and D-Galn. To predict potential targets and mechanisms of QUE in ALF treatment, transcriptomics, network pharmacology, molecular docking techniques, and ChIP were employed. The expression level related to mitophagy, apoptosis, and signaling pathways were detected by CCK8, IHC, IF staining, TUNEL, RT-qPCR, TEM, Western blotting, ELISA, and flow cytometry.
RESULTS: Network pharmacology and transcriptomics revealed common targets between QUE and ALF. Enrichment analysis showed that the anti-ALF targets of QUE were significantly associated with mitochondria and NF-κB-related pathways. Subsequent experiments showed that QUE pretreatment significantly alleviated the loss of hepatocyte viability, enhanced mitochondrial membrane potential, activated mitophagy, and promoted the clearance of damaged mitochondria, thereby reducing ROS accumulation, significantly reducing cell apoptosis and inflammatory responses, reducing ALT and AST levels, and improving liver…
Read the paper
Related studies
- Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence
- Phenolic-protein interactions: insight from in-silico analyses – a review
- In Silico Discovery of Candidate Drugs against Covid-19
- Neuropharmacological Effects of Quercetin: A Literature-Based Review
- In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting
- Effect of Quercetin Rich Onion Extracts on Bacterial Quorum Sensing
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.