Atherosclerosis is the major worldwide cause of mortality for patients with
coronary heart disease. Many
traditional Chinese medicine compound prescriptions for
atherosclerosis treatment have been tried in patients. Dan-Lou prescription, which is improved from
Gualou-Xiebai-Banxia decoction, has been used to treat chest discomfort (
coronary atherosclerosis) for approximately 2,000 years in China. Although the anti-inflammatory activities of Dan-Lou prescription have been proposed previously, the mechanism remains to be explored. Based on the interaction between
inflammation and
atherosclerosis, we further investigated the effect of Dan-Lou prescription on macrophage-derived foam cell formation and disclosed the underlying mechanisms. In the oxidative
low-density lipoprotein (
ox-LDL) induced foam cells model using murine macrophage RAW 264.7 cells, the
ethanol extract from Dan-Lou prescription (EEDL) reduced
ox-LDL uptake and
lipid deposition by inhibiting the
protein and
mRNA expression of
Toll-like receptor (TLR)4 and
scavenger receptor (SR)B1. After stimulation with
ox-LDL, the metabolic profile of macrophages was also changed, while the intervention of the EEDL mainly regulated the metabolism of
isovalerylcarnitine,
arachidonic acid,
cholesterol,
aspartic acid,
arginine, lysine,
L-glutamine and
phosphatidylethanolamine (36:3), which participated in the regulation of the inflammatory response,
lipid accumulation and cell apoptosis. In total, 27
inflammation-related gene targets were screened, and the
biological mechanisms, pathways and
biological functions of the EEDL on macrophage-derived foam cells were systemically analyzed by Ingenuity Pathway Analysis system (IPA). After verification, we found that EEDL alleviated
ox-LDL induced macrophage foam cell formation by antagonizing the
mRNA and
protein over-expression of PPARγ, blocking the phosphorylation of IKKα/β, IκBα and NF-κB p65 and maintaining the expression balance between Bax and Bcl-2. In conclusion, we provided evidences that Dan-Lou prescription effectively attenuated macrophage foam cell formation via the TLR4/NF-κB and PPARγ signaling pathways.