Abstract
Background: 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 in vivo and in vitro experiments. Methods: 1) In vivo 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) In vitro 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 in vitro. The mRNA and protein expression of related molecules involved in LXRα-LPCAT3-ERS pathway were detected using RT-qPCR and Western blot. Results: 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. Conclusion: KP may decrease the expression level of LXRα and LPCAT3, thus improve ERS and reduce hepatic steatosis and inflammation.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome, which includes simple steatosis, steatohepatitis (NASH), liver fibrosis and cirrhosis and their clinical consequences (Nobili et al, 2019)
In the non-alcoholic steatohepatitis (NASH) mouse model, KP can significantly reduce the expression of LXRα, Lysophosphatidylcholine acyltransferase 3 (LPCAT3) and endoplasmic reticulum stress (ERS)-related factors Protein kinase R-like ER kinase (PERK), eIF2α, activating transcription factor 6 (ATF6), ATF4, X-box-binding protein 1 (XBP1), C/EBP homologous protein (CHOP), IRE1α and GRP78
In the palmitic acid/oleic acid (PA/OA)-induced cell model, KP could decrease the content of triglyceride and lipid droplets, and decrease the expression of Liver X receptors (LXRs) α, LPCAT3 and ERS related factors PERK, eIF2α, ATF6, ATF4, XBP1, CHOP, IRE1α and GRP78
Summary
Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome, which includes simple steatosis, steatohepatitis (NASH), liver fibrosis and cirrhosis and their clinical consequences (Nobili et al, 2019). NASH is usually associated with more severer liver cirrhosis and liver cancer (Friedman et al, 2018). NAFLD is one of the leading cause of liver disease in the world, which is closely linked to the increased prevalence of obesity and metabolic diseases. NAFLD prevalence varies widely from the Asiapacific region, ranging from about 5 to 32% (Younossi et al, 2018). One third of NAFLD patients will progress to NASH (Takahashi and Fukusato, 2014). 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 in vivo and in vitro experiments
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