Baolier capsule (BLEC), a traditional Mongolian formulation, is prescribed for managing hypercholesterolemia and atherosclerosis (AS). Yet, its therapeutic efficacy, key constituents, and molecular actions in these disorders remain insufficiently defined. This work sought to clarify the pharmacodynamic profile of BLEC, identify its principal bioactive molecules, and delineate its mechanisms against hypercholesterolemia and AS. Liver-specific LXRα knockout ApoE−/− mice were generated via adeno-associated virus injection through the tail vein. ApoE−/− mice were fed a high-fat diet to establish hyperlipidemia and AS models. Oil Red O staining of the aorta or liver was applied to evaluate the influence of oral BLEC, piperine, statins, or ezetimibe on plaque formation or hepatic lipid accumulation according to the study design. Serum lipid panels and cholesterol efflux markers were assessed using biochemical tests. Transcriptome analyses were used to determine BLEC-induced transcriptional alterations in the liver. HPLC-MS/MS quantified BLEC and its major constituents in hepatic tissue. Western blotting and qRT-PCR were employed to measure LXRα, ABCA1, ABCG5, ABCG8, and CYP7A1 expression.
BLEC lowered lipid accumulation in both serum and hepatic tissue and mitigated AS by enhancing cholesterol disposal. BLEC and piperine, the dominant compounds identified in liver samples, stimulated LXRα, thereby elevating ABCA1, ABCG5, ABCG8, and CYP7A1 expression, which in turn facilitated cholesterol transfer to HDL and its removal through bile and feces. In addition, piperine showed cooperative beneficial effects when combined with atorvastatin or ezetimibe, two standard lipid-lowering medications. BLEC and its primary active constituent, piperine, boost cholesterol elimination, reduce circulating cholesterol, suppress AS progression, and demonstrate strong potential for clinical translation.
