Differential neuroprotective mechanisms of rosemary and carnosic acid in cerebral ischemia-reperfusion injury

Rosemary is a traditional Chinese medicinal herb recognized for its therapeutic potential in cardiovascular and cerebrovascular diseases. Its primary active constituent, carnosic acid, has been shown to reduce infarct volume in ischemic stroke models. However, the mechanisms underlying the effects of rosemary and carnosic acid, and their specific actions in ischemic stroke remain incompletely understood. In this study, we evaluated the therapeutic effects of rosemary and carnosic acid using a middle cerebral artery occlusion/reperfusion model, and predicted their mechanisms of action network pharmacology and molecular docking approaches, with key targets subsequently validated using quantitative PCR analysis. The results showed that both rosemary and carnosic acid significantly reduced infarct volume and improved neurological function. Rosemary treatment increased spleen weight, suggesting a potential immunomodulatory role, whereas carnosic acid had no significant effect on spleen weight. Network pharmacology analysis indicated that rosemary regulated multiple molecular pathways, including the VEGF, PI3K-Akt, and TNF signaling pathways, while carnosic acid primarily influenced pathways associated with apoptosis and inflammation. Molecular docking and qPCR validation further demonstrated that carnosic acid modulated apoptosis through key targets such as TNF-α, TP53, MMP9, and PPARG. Rosemary and carnosic acid exert neuroprotective effects in cerebral ischemia-reperfusion injury through distinct mechanisms, demonstrating their potential as complementary therapeutic agents for ischemic stroke.