Myristic Fragransinhibit Atherosclerosis By Upregulating Macrophage-derived ABCA1 Expression And Cholesterol Efflux

【Background and Aim】Atherosclerosis(AS)is caused by many factors such as heredity,lipid metabolism and environment.The abnormal expression of lipid metabolism related genes is the key factor affecting the occurrence and development of AS.As an important lipid metabolism related gene,ATP binding transporter A1(ABCA1)is the key protein of reverse cholesterol transport(RCT)and an important target for the prevention and treatment of AS.MF(Myristica fragrans)is a kind of medicinal plant.It has been reported that MF can improve insulin resistance,hyperlipidemia and anti-inflammatory action.Recently,MF have been reported that it was beneficial in the process of AS.Therefore,we aim to research effect of MF on atherosclerosis and its mechanism,which is expected to provide a new treatment direction for the prevention and treatment of As.【Methods】THP-1-derived macrophages were incubated with 50μg/ml ox-LDL to form foam cells,followed by related experiments.Foam cells were treated with different concentrations(0,2.5,5,10,20 μM)of Myristica fragrans for 24 h or 10 μM Myristica fragrans for different time periods(0,6,12,24,48h).To examine the intracellular lipid contents and cholesterol efflux from cellular.The m RNA and protein levels of ABCA1 were examined by RT-PCR and western blot.THP-1-derived macrophages were incubated with 10 μg/L MF and 50 μg/ml ox-LDL.Foam cells were treated with 10 μmol /L Myristica fragrans for 24 h or/and GGPP.Detection of LXRα and LXRβ and ABCA1 expression using RT-PCR and western blot.Foam cells were treated with 10 μM Myristica fragrans for 24 h or/and GATA3,Detection of the promoter activity of LXRα using CHIP.The m RNA and protein levels of GATA3 were detected by RT-PCR and western blot.Foam cells were treated with10 μM Myristica fragrans for 24 h and GATA3 si RNA,The m RNA levels of GATA3 detected by RT-PCR,The m RNA levels of GATA3 detected by RT-PCR.The m RNA and protein levels of LXRα and ABCA1 were detected by RT-PCR and western blot.THP-1-derived macrophages were treated with 10 μM Myristica fragrans for 24 h or/and 50 μg/ml ox-LDL,detection of The levels of TNF-α,IL-1β,IL-6,IL-10 using ELISA.【Results】1.Myristica fragrans accelerates cholesterol efflux from THP-1-derived macrophages.2.Myristica fragrans upregulated ABCA1 expression.3.LXRα-mediated the upregulation of ABCA1 by Myristica fragrans.4.GATA3 participates in Myristica fragrans-induced LXRαexpression.5.Myristica fragrans reduced pro-inflammatory cytokines secreted from THP-1-derived macrophages.【Conclusions】1.Myristica fragrans upregulates the expression of ABCA1 and reduces the lipid accumulation in THP-1-derived macrophages through GATA3 / LXR α pathway.2.Anti-inflammatory action of Myristica fragrans depends on the decrease of pro-inflammatory factors.