Quercetin-liposomes effectively regulated the Nrf2/Keap1 and NF-κB/P38 MAPK signaling pathways and protected the liver against paracetamol-induced damage

槲皮素脂质体有效调节Nrf2/Keap1和NF-κB/P38 MAPK信号通路,并保护肝脏免受对乙酰氨基酚引起的损伤。

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Abstract

The prevalence of hepatotoxicity has sharply increased worldwide in recent decades. Our study aimed to enhance quercetin's effectiveness against paracetamol (PCM)-induced hepatotoxicity using a quercetin liposome nano formulation. The quercetin liposome (QL) nano formula was fabricated by applying the thin-film hydration method. It was examined via dynamic light scattering, confirmed with a transmission electron microscope (TEM), and followed by assessments of drug-loading capacity, encapsulation efficiency (EE%), and Fourier transform infrared (FTIR) spectroscopy. The release features and cell cytotoxicity were also assessed. The in vivo parameters were completed. We effectively synthesized and characterized the quercetin liposome nanoformula with a 501.9 nm particle size and a -22.8 mV zeta potential. TEM imaging showed that quercetin liposomes were spherical. The EE% for the optimized formulation was 77.1 %. FTIR test confirmed the quercetin liposome spectra. Sustained release behavior of about 67.45 % of quercetin was released from liposomes by 24 h. The IC50 value was reduced from 71.32 µg/ml to 51.28 µg/ml for quercetin and quercetin-loaded liposomes. For the in vivo study, quercetin liposome improved all the altered biochemical markers, alleviating the levels of Malondialdehyde (MDA), Nitric oxide (NO), Superoxide dismutase (SOD), and Glutathione peroxidase (GPx), and upregulating Nuclear factor erythroid 2-related factor 2 (Nrf2) with a downregulation of Kelch-like ECH-associated protein 1 (Keap1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and p38 Mitogen-activated protein kinase (P38 MAPK) gene expression that paralleled the histopathological amelioration. Our results suggested that the quercetin liposome nano formulation had potent hepatoprotective activity through ameliorating biochemical indicators, oxidative stress markers, upregulation of anti-apoptotic genes, and improvement in the histopathological index.

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