Kaempferol (KP) has a variety of biological effects such as anti-inflammatory, anti-oxidant, anti-aging and cardiovascular protection. Whether KP has a therapeutic effect on non-alcoholic steatohepatitis (NASH), and the detailed mechanism is currently unclear. This study aims to explore the mechanism of KP in the treatment of NASH through and experiments. 1) experiment: In the C57BL/6 NASH mice model induced by high fat diet (HFD), KP was administered by gavage at a dose of 20 mg/kg/day. 2) experiment: Palmitic acid/Oleic acid (PA/OA, 0.375/0.75 mM) was used to intervene HepG2 and AML12 cells to establish a steatosis cell model. Three concentrations of KP, low (20 μmol/L), medium (40 μmol/L) and high (60 μmol/L) were used . The mRNA and protein expression of related molecules involved in LXRα-LPCAT3-ERS pathway were detected using RT-qPCR and Western blot. In the NASH mouse model, KP can significantly reduce the expression of LXRα, LPCAT3 and ERS-related factors PERK, eIF2α, ATF6, ATF4, XBP1, CHOP, IRE1α and GRP78. In the PA/OA-induced cell model, KP could decrease the content of triglyceride and lipid droplets, and also decrease the expression of LXR α, LPCAT3 and ERS related factors PERK, eIF2α, ATF6, ATF4, XBP1, CHOP, IRE1α and GRP78. KP may decrease the expression level of LXRα and LPCAT3, thus improve ERS and reduce hepatic steatosis and inflammation.
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http://dx.doi.org/10.3389/fphar.2021.690736 | DOI Listing |
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College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, Tianjin 300457, China. Electronic address:
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Section of Preclinical Disease Biology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.
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