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Myristica fragrans is a traditional herbal medicine and has been shown to alleviate the develop-ment of atherosclerosis.However,the anti-atherogenic mechanisms of M.fragrans are still to be addressed.In this study,we explored the effect of M.fragrans on lipid metabolism and inflam-mation and its mechanisms in THP-1-derived macrophages.The quantitative polymerase chain reaction and western blot analysis results showed that M.fragrans promotes cholesterol efflux from THP-1-derived macrophages and reduces intracellular total cholesterol,cholesterol ester,and free cholesterol contents in a dose- and a time-dependent manner.Further study found that liver X receptor alpha (LXRα) antagonist GGPP significantly blocked the upregulation of ABCA1 expres-sion with M.fragrans treatment.In addition,chromatin immunoprecipitation assay confirmed that GATA binding protein 3 (GATA3) can bind to the LXRα promoter,and inhibition of GATA3 led to the downregulation of LXRα and ATP-binding cassette subfamily A member 1 expression.Further-more,M.fragrans reduced lipid accumulation,followed by decreasing tumor necrosis factor-α,interleukin (IL)-6,and IL-1 β and increasing IL-10 produced by THP-1-derived macrophages.There-fore,M.fragrans is identified as a valuable therapeutic medicine for atherosclerotic cardiovascular disease.