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Journal of Nutritional Biochemistry

Journal of Nutritional Biochemistry

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Quercetin ameliorates nonalcoholic fatty liver disease (NAFLD) via the promotion of AMPK-mediated hepatic mitophagy.

Published:1 October 2023 DOI: 10.1016/j.jnutbio.2023.109414 PMID: 37423322
Peng Cao , Yi Wang , Cong Zhang , Mitchell A. Sullivan , Wen Chen , Xiang Jing , Huifan Yu , Fei Li , Qu Wang , Zhongshi Zhou , Qi Wang , Wen Tian , Zhenpeng Qiu , Lianxiang Luo

Abstract

The global incidence of nonalcoholic fatty liver disease (NAFLD) has been surging in recent years, however, no drug is currently approved to treat this disease. Quercetin, a natural flavonoid abundant in plants and fruits, has been reported to alleviate NAFLD, however, the exact molecular mechanism remains unclear. This study aims to further elucidate its potential mechanism of action. The beneficial effects and the underlying mechanism of quercetin in alleviating NAFLD were explored both in vitro and in vivo, by employing chemical inhibitors of autophagosomes (3-methyladenine, 3-MA), autolysosomes (chloroquine, CQ), AMPK (Compound C, CC) and SIRT1 (selisistat, EX-527). The levels of intracellular lipids, reactive oxygen species, mitochondria function, autophagy, and mitophagy were assessed by fluorescent labeling and examined using flow cytometry or confocal microscopy. Key protein expressions of autophagy, mitophagy, and inflammation were also determined. In vivo, quercetin was shown to dose-dependently effectively alleviate NAFLD, but intraperitoneal injection of 3-MA could block the beneficial effects of quercetin on body weight, liver weight, serum ALT/AST, hepatic ROS and inflammation. In vitro, quercetin could reduce intracellular lipids (Nile Red staining) and ROS/DHE accumulation, which could be also blocked by 3-MA or CQ. Furthermore, we found that CC could abrogate the protective effects of quercetin on lipid and ROS accumulation in vitro. Also, CC abolished the proautophagic and anti-inflammatory effects of quercetin, as shown by western blot determination and Lyso-Tracker labeling. Importantly, mitophagy, a specific form of mitochondria-targeted autophagy, was enhanced by quercetin, as demonstrated by PINK1/Parkin protein variation and immunofluorescence colocalization of autophagosomes and mitochondria, which could also be blocked by the intervention of CC. This study demonstrates that quercetin prevents NAFLD through AMPK-mediated mitophagy and suggests that promoting mitophagy via an upregulation of AMPK may be a promising therapeutic strategy against NAFLD.

Substances (20)

Materials
Procduct Name CAS Molecular Formula Supplier Price
3-METHYLADENINE 5142-23-4 C6H7N5 393 suppliers $12.00-$4500.00
3-METHYLADENINE 5142-23-4 C6H7N5 393 suppliers $12.00-$4500.00
3-METHYLADENINE 5142-23-4 C6H7N5 393 suppliers $12.00-$4500.00
3-METHYLADENINE 5142-23-4 C6H7N5 393 suppliers $12.00-$4500.00
6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE 49843-98-3 C13H13ClN2O 264 suppliers $20.00-$1949.90
6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE 49843-98-3 C13H13ClN2O 264 suppliers $20.00-$1949.90
6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE 49843-98-3 C13H13ClN2O 264 suppliers $20.00-$1949.90
6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE 49843-98-3 C13H13ClN2O 264 suppliers $20.00-$1949.90
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00

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