Mechanistic elucidation of Panax ginseng in improving atherosclerosis via multidimensional artificial intelligence computing coupled with experimental validation.

BACKGROUND: Atherosclerosis (AS) is the core pathological foundation of cardiovascular and cerebrovascular diseases, and its efficient prevention is pivotal to lowering related mortality and disability. Panax ginseng confers remarkable cardiovascular protection, whereas its anti-atherosclerotic efficacy and intrinsic mechanisms remain poorly elucidated, restricting its clinical translation. This study sought to decipher the mechanism underlying Panax ginseng mediated AS improvement via multidimensional artificial intelligence (AI) computation integrated with experimental validation. METHODS: UPLC-Q-TOF-MS/MS was employed to characterize Panax ginseng chemical constituents. Multidimensional AI computation strategies, including differential expression analysis, weighted gene co-expression network analysis, machine learning, coupled with transcriptome and database mining were utilized to screen core anti-AS targets. Meanwhile, the molecular docking, molecular dynamics simulation, cellular thermal shift assay and in vivo experiments combined with multivariate statistical analysis were performed for target verification. RESULTS: 55 compounds from Panax ginseng and 117 anti-AS potential targets were identified. The RXRA was recognized as the pivotal hub target via machine learning. The 14 components in Panax ginseng displayed stable binding with RXRA in molecular docking, dynamics simulations and cellular thermal shift assay. Ultimately, the experiments in vivo confirmed that Adenine, a representative compound of Panax ginseng, alleviated AS via regulating RXRA expression. CONCLUSION: Panax ginseng exerts anti-atherosclerotic effects by targeting RXRA, with 14 active compounds (e.g., Adenine) serving as the key material basis for its pharmacological activity.