Zhixiong Capsule (ZXC), a traditional Chinese patent medicine, prevents atherosclerotic plaque formation in rabbit carotid artery and the related mechanism investigation based on network pharmacology and biological research

Abstract Background and aims Chinese patent medicine Zhixiong Capsule (ZXC) has been used in clinical treatment against blood stasis-induced dizziness and headache for many years in China. Hypothesis/Purpose Recent clinical observations demonstrated a good efficacy of ZXC against atherosclerotic plaque formation in carotid arteries. The aims of this study were to verify the plaque-preventing efficacy of ZXC in animals and to investigate the underlying mechanisms. Study design/Methods ZXC (185 mg/kg and 370 mg/kg) was administrated to rabbits which received collar implantation accompanied with high fat diet administration (12 days). The blood-dissolved components of ZXC were identified by an UPLC-QTOF-MS method. The key components and targets of ZXC were then predicted based on network pharmacology analysis and biological investigations. Results Compared with vehicle control group, ZXC administration (185 mg/kg) significantly prevented plaque formation and attenuated intima thickening in the collar-implanted carotid arteries, markedly decreased blood lipid level, and increased plasma IL-4 level in rabbits. A total of 23 blood-dissolved components were identified. Four ingredients (namely, kaempferol, daidzein, puerarin, miltirone) along with leech, and three targets (namely, JUN, FOS and TP53) were recognized to play important roles for ZXC bioactivity. Conclusion It could be concluded that ZXC could be applied to prevent atherosclerotic plaque formation and intimal thickening in carotid arteries at the current clinical dose.