Xiang Hongjiao, Shao Mingmei, Lu Yifei, Wang Junmin, Wu Tao, Ji Guang
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2021 Jun 28;12:690736. doi: 10.3389/fphar.2021.690736. eCollection 2021.
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.
山奈酚(KP)具有多种生物学效应,如抗炎、抗氧化、抗衰老和心血管保护作用。KP对非酒精性脂肪性肝炎(NASH)是否具有治疗作用及其具体机制目前尚不清楚。本研究旨在通过[具体实验1]和[具体实验2]实验探究KP治疗NASH的机制。1)[具体实验1]实验:在高脂饮食(HFD)诱导的C57BL/6 NASH小鼠模型中,以20 mg/kg/天的剂量通过灌胃给予KP。2)[具体实验2]实验:用棕榈酸/油酸(PA/OA,0.375/0.75 mM)干预HepG2和AML12细胞以建立脂肪变性细胞模型。使用三种浓度的KP,即低浓度(20 μmol/L)、中浓度(40 μmol/L)和高浓度(60 μmol/L)。采用RT-qPCR和蛋白质免疫印迹法检测LXRα-LPCAT3-ERS途径相关分子的mRNA和蛋白质表达。在NASH小鼠模型中,KP可显著降低LXRα、LPCAT3和ERS相关因子PERK、eIF2α、ATF6、ATF4、XBP1、CHOP、IRE1α和GRP78的表达。在PA/OA诱导的细胞模型中,KP可降低甘油三酯和脂滴含量,同时降低LXRα、LPCAT3和ERS相关因子PERK、eIF2α、ATF6、ATF4、XBP1、CHOP、IRE1α和GRP78的表达。KP可能通过降低LXRα和LPCAT3的表达水平,从而改善内质网应激(ERS)并减轻肝脏脂肪变性和炎症。