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Biomed Pharmacother ; 157: 114005, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36384052

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most common among lipid metabolism disorders. Autophagy plays an important role in lipid metabolism in NAFLD. Pueraria flavonoids, the main active ingredients of Pueraria lobata, exert antioxidant and anti-inflammatory effects. Herein, we report the potential lipid-lowering and anti-inflammatory effects of Pueraria flavonoids on NAFLD induced by a high-fat diet. In vivo and in vitro experiments showed that Pueraria flavonoids reduced intracellular lipid deposition by inhibiting lipid synthesis and the release of pro-inflammatory cytokines. We analyzed the autophagy flux by mRFP-GFP-LC3 plasmid transfection to assess the role of autophagy in intracellular scavenging. After treating mice fed on high fat and HepG2 cells with Pueraria flavonoids, the number of autophagosomes increased significantly, along with the level of autophagy. The autophagy loss after siRNA transfection aggravated lipid deposition and the release of inflammatory cytokines. Mechanistically, Pueraria flavonoids trigger autophagy through PI3K/Akt/mTOR signaling pathway to reduce lipid deposition and inflammation. In summary, our results showed that Pueraria flavonoids stimulated autophagy by inhibiting the PI3K/Akt/mTOR signaling pathway, thereby reducing intracellular lipid accumulation and inflammation levels and alleviating NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Pueraria , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Obesos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Camundongos Endogâmicos C57BL , Autofagia , Transdução de Sinais , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Lipídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo
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